Sample records for lyp-1-conjugated liposomes l-ls

  1. LyP-1-conjugated doxorubicin-loaded liposomes suppress lymphatic metastasis by inhibiting lymph node metastases and destroying tumor lymphatics

    Energy Technology Data Exchange (ETDEWEB)

    Yan Zhiqiang; Zhan Changyou; Wen Ziyi; Feng Linglin; Wang Fei; Liu Yu; Yang Xiangkun; Dong Qing; Liu Min; Lu Weiyue, E-mail: [Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203 (China)


    Lymphatic metastasis can be greatly promoted by metastases growth and lymphangiogenesis in lymph nodes (LNs). LyP-1, a cyclic peptide, is able to specifically bind with tumor cells and tumor lymphatics in metastatic LNs. This work aimed to use LyP-1-conjugated liposomes (L-LS) loaded with doxorubicin (DOX) (L-LS/DOX) to suppress lymphatic metastasis by inhibiting both metastases and tumor lymphatics in LNs. L-LS were prepared and exhibited sizes around 90 nm and spherical morphology as characterized by transmission electron microscopy. The in vitro cellular studies showed that LyP-1 modification obviously increased liposome uptake by MDA-MB-435 tumor cells and enhanced the cytotoxicity of liposomal DOX. A popliteal and iliac LN metastases model was successfully established by subcutaneous inoculation of tumor cells to nude mice. The immunofluorescence staining analysis indicated that LyP-1 modification enabled specific binding of liposome with tumor lymphatics and enhanced the destroying effect of liposomal DOX on tumor lymphatics. The in vivo fluorescence imaging and pharmacodynamic studies showed that LyP-1 modification increased liposome uptake by metastatic LNs and that L-LS/DOX significantly decreased metastatic LN growth and LN metastasis rate. These results suggested that L-LS/DOX were an effective delivery system for suppressing lymphatic metastasis by simultaneously inhibiting LN metastases and tumor lymphatics.

  2. Relations Between Helicity Coupling Amplitude and L-S Coupling Amplitude

    Institute of Scientific and Technical Information of China (English)

    WU Ning; RUAN Tu-Nan


    Relations between helicity coupling amplitude and L-S coupling amplitude are discussed. The equivalence condition for these two kinematic analysis methods and the limitations of the L-S coupling amplitude are also studied in this paper.``

  3. Atomic electronic states: the L-S and j-j coupling schemes and their correlation

    CERN Document Server

    Li, Wai-Kee


    In the first part of this paper, we review the assumption of the L-S coupling scheme, with which we derive the electronic states arising from a given atomic configuration. Then, with the aid of the spectral data of Group 15 elements, it becomes clear that the assumption of the L-S coupling scheme is no longer valid as we go farther and farther down the Periodic Table. In the second part, we introduce the j-j coupling scheme, which is seldom covered in standard inorganic chemistry texts, and contrast the assumptions of the two schemes. Next, we use two worked examples to demonstrate the derivation of electronic states with the j-j coupling scheme. Finally, the correlation between the states derived by L-S and j-j schemes is pictorially shown. It is believed a student, by also studying j-j coupling schemes (by no means a difficult task) along with the L-S scheme, will gain a better understanding of the concept of atomic electronic states.

  4. Effect of L.S. Vygotsky's Ideas on the Development of Russian Didactics (Primary School) (United States)

    Vinogradova, N. F.


    This article characterizes the changes that occurred and are occurring in the didactics of primary school as an effect of L.S. Vygotsky's psychological ideas. It underscores the characteristic features of the step-by-step convergence of psychology and pedagogy and discloses the reasons psychological knowledge is not used sufficiently to organize…

  5. 'Mrs L.'s case': a celebrated South Australian surgical case. (United States)

    Elmslie, R G


    This paper concerns a dispute at the Adelaide Hospital in September 1896 between Professor Archibald Watson, Pathologist, Honorary Consulting Surgeon and sole remaining University teacher at the hospital, and Alexander Disney Leith Napier, who had arrived from England to fill the place of the honorary surgeons who had resigned from the hospital. Watson accused Napier of incompetence in his management of 'Mrs L.', who died after a femoral hernia operation. Mrs L had a form of internal hernia causing intestinal obstruction, whereas all the medical attendants, including Watson, originally thought an old femoral hernia was the cause of her illness. By fortuitous coincidence the operation on the femoral hernia could have cured the internal hernia if the band of omentum attached to the femoral hernia had been divided. Watson became aware of the band at the post-mortem and then asserted that the operation should have taken it into account. Napier complained to the Board of the Hospital, alleging that Watson had misrepresented the facts when he conducted the post-mortem on the patient and that he was disloyal to the hospital. The Board found the complaint proved and invited Watson to resign; he declined and was dismissed. Undaunted, Watson circulated a privately printed pamphlet (entitled 'Mrs L.'s case'), which re-stated the events of the case and graphically described his post-mortem findings. It was submitted to the Chairman of a Select Committee of the Legislative Council of South Australia established to review the running of the hospital. The Committee recommended the setting up of a Royal Commission but the Government let the matter lapse.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Water physics and chemistry data from bottle casts from the CHESAPEAKE L/S and other platforms from 01 January 1957 to 31 December 1957 (NODC Accession 7000291) (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Water physics and chemistry data were collected from bottle casts from the CHESAPEAKE L/S and other platforms from 01 January 1957 to 31 December 1957. Data were...

  7. Water physics and chemistry data from bottle casts from the CHESAPEAKE L/S and other platforms from 28 November 1955 to 31 December 1956 (NODC Accession 6800101) (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Water physics and chemistry data were collected from bottle casts from the CHESAPEAKE L/S and other platforms from 28 November 1955 to 31 December 1956. Data were...

  8. L.S. Vygotsky's Principle "One Step in Learning — A Hundred Steps in Development": In Search of Evidence

    Directory of Open Access Journals (Sweden)

    V.K. Zaretsky


    Full Text Available On the basis of L.S. Vygotsky's published works the paper attempts to trace the dynamics of his concepts of child development and to provide evidence supporting Vygotsky's statement that one step in learning equals a hundred in development, which is one of the key principles of culturalhistorical theory in its application to child development. This statement is put in a row with two other major principles: one arguing that learning precedes development and the other referring to the zone of proximal development. The paper outlines a multivector model of the zone of proximal development as one of the conceptual tools of the reflective and activity approach to helping children overcome learning difficulties and promoting their development. The paper also describes a case study in which an orphan child with a disability received psychological and educational support that obviously contributed to the child's development. It is argued that L.S. Vygotsky's idea of the specific relationship between learning and development has fundamental theoretical and practical implications, in particular, for working with children with special needs

  9. L-S mass transfer in G-L-S countercurrent magnetically stabilized bed with amorphous alloy SRNA-4 catalyst

    Institute of Scientific and Technical Information of China (English)

    Wei; Li; Baoning; Zong; Xiaofang; Li; Xiangkun; Meng; Jinli; Zhang


    Liquid-solid (L-S) mass transfer coefficients (Ks) were characterized in a gas-liquid-solid (G-L-S) three-phase countercurrent magnetically stabilized bed (MSB) using amorphous alloy SRNA-4 as the solid phase. Effects of superficial liquid velocity, superficial gas velocity, magnetic field strength, liquid viscosity and surface tension were investigated. Experimental results indicated that the external magnetic field increased Ks in three-phase MSB, as compared to those in conventional G-L-S fluidized beds; that Ks increased with magnetic field strength, superficial gas and liquid velocities and decreased with liquid viscosity and surface tension; and that Ks showed uniform axial and radial distributions except for small increases close to the wall. Dimensionless correlations were established to estimate Ks of the G-L-S countercurrent MSB using SRNA-4catalyst, with an average error of 3.6%.

  10. “Lines of Mourning”: On the Issue of National and Cultural Self-Determination of L.S. Vygotsky

    Directory of Open Access Journals (Sweden)

    Sobkin V.S.


    Full Text Available The paper presents the full text of a work by L.S. Vygotsky “Lines of Mourning” (1916 along with detailed commentaries. This article was the first of the three published in the Jewish periodical Noviy Put’ that can be considered a triptych dedicated to the issues of national, cultural and religious traditions and their relation with modern times. The text and commentaries provide an insight into personal meanings and attitudes of young Vygotsky in the situation of political and value/normative uncertainty. This enables us to reconstruct the features of social, political, national and ethic self-definition of the scientist and to reveal the grounds and values underlying the cultural-historical approach. Special attention is brought to the dialogic nature of the Jewish and Russian culture. In the commentaries we also focus on the specifics of artistic and reflective position of Vygotsky in relation to pre-revolutionary events that took place at that time: understanding this allows us to comprehend a whole set of social, political, moral, ethic and truly psychological problems that would later on be reflected in his scientific works. Another section of our commentaries is centered on the analysis of the article’s style and composition and its multi-layered structure.

  11. Electrodialytic extraction of heavy metals from Greenlandic MSWI fly ash as a function of remediation time and L/S ratio

    DEFF Research Database (Denmark)

    Kirkelund, Gunvor Marie; Jensen, Pernille Erland; Ottosen, Lisbeth M.


    The management of Greenlandic municipal solid waste incineration (MSWI) fly ash could be improved. Presently, the fly ash is disposed of in Norway as the fly ash is classified as hazardous waste. Fly ash contains high amounts of leachable heavy metals, but also resources that could be beneficial...... for reuse. In electrodialytic remediation a direct current is applied to a contaminated particulate material to remove heavy metals from the material. In this study, electrodialytic remediation was applied to a Greenlandic MSWI fly ash from a small waste incinerator in Ilulissat. The fly ash...... lasting 14 days with L/S 10, up to 60 % Cd, 45 % Zn, 20 % Ni and Ba was removed. Regardless of the remediation time and L/S ratio, the fraction of soluble Ba, Cr and Pb decreased due to the electrodialytic remediation. The electrodialytic remediation method showed potential as a treatment method...

  12. Liposomal chemotherapeutics. (United States)

    Gentile, Emanuela; Cilurzo, Felisa; Di Marzio, Luisa; Carafa, Maria; Ventura, Cinzia Anna; Wolfram, Joy; Paolino, Donatella; Celia, Christian


    Currently, six liposomal chemotherapeutics have received clinical approval and many more are in clinical trials or undergoing preclinical evaluation. Liposomes exhibit low toxicity and improve the biopharmaceutical features and therapeutic index of drugs, thereby increasing efficacy and reducing side effects. In this review we discuss the advantages of using liposomes for the delivery of chemotherapeutics. Gemcitabine and paclitaxel have been chosen as examples to illustrate how the performance of a metabolically unstable or poorly water-soluble drug can be greatly improved by liposomal incorporation. We look at the beneficial effects of liposomes in a variety of solid and blood-borne tumors, including thyroid cancer, pancreatic cancer, breast cancer and multiple myeloma.

  13. Significance of Cultural-Historical Theory of Psychological Development of L.S. Vygotsky for the Development of Modern Models of Social Cognition and Psychotherapy

    Directory of Open Access Journals (Sweden)

    Kholmogorova A.B.,


    Full Text Available The article acknowledges the situation of methodical crisis in modern research of social cognition related to the domination of reductive approaches that ignore the uniqueness of human psyche. Heuristicity of concepts of cultural-historical theory of psychological development of L.S. Vygotsky, which serves to overcome the apparent inconsistencies is substantiated. Models of social cognition based on the principles of cultural-historical psychology are described, those being the model of social cognition within phylogenesis of M. Tomasello, and the model of social cognition within ontogenesis of C. Fernyhough. Current situation in the area of mental health is reviewed from the standpoint of cultural-historical psychology, its specifics reflected in the increased burden on reflexive functions, that is, skills lying within the sphere of social cognition is substantiated. Modern psychotherapeutic apparatus directed to compensate social cognition deficits due to various psychiatric disorders is reviewed. The assumption that adolescense is sensitive period for the development of higher forms of social cognition is made, and a summary of researches supporting this assertion is presented. Main contradictions of modern-day maturing are enunciated. To conclude the presented theoretical analysis, a comprehensive multiple-factor model of social cognition is presented based on concepts of cultural-historical theory of L.S. Vygotsky.

  14. Prediction of fetal lung maturity using the lecithin/sphingomyelin (L/S) ratio analysis with a simplified sample preparation, using a commercial microtip-column combined with mass spectrometric analysis. (United States)

    Kwak, Ho-Seok; Chung, Hee-Jung; Choi, Young Sik; Min, Won-Ki; Jung, So Young


    Fetal lung maturity is estimated using the lecithin/sphingomyelin ratio (L/S ratio) in amniotic fluid and it is commonly measured with thin-layer chromatography (TLC). The TLC method is time consuming and technically difficult; however, it is widely used because there is no alternative. We evaluated a novel method for measuring the L/S ratio, which involves a tip-column with a cation-exchange resin and mass spectrometry. Phospholipids in the amniotic fluid were extracted using methanol and chloroform. Choline-containing phospholipids such as lecithin and sphingomyelin were purified by passing them through the tip-column. LC-MS/MS and MALDI-TOF were used to directly analyze the purified samples. The L/S ratio by mass spectrometry was calculated from the sum peak intensity of the six lecithin, and that of sphingomyelin 34:1. In 20 samples, the L/S ratio determined with TLC was significantly correlated with that obtained by LC-MS/MS and MALDI-TOF. There was a 100% concordance between the L/S ratio by TLC and that by LC-MS/MS (kappa value=1.0). The concordance between the L/S ratio by TLC and that by MALDI-TOF was also 100% (kappa value=1.0). Our method provides a faster, simpler, and more reliable assessment of fetal lung maturity. The L/S ratio measured by LC-MS/MS and MALDI-TOF offers a compelling alternative method to traditional TLC. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Developing the Ideas of the Scientific School of L.S. Vygotsky: Scientific Publications of the Journal “Cultural-Historical Psychology” (2005—2016

    Directory of Open Access Journals (Sweden)

    Shvedovskaya A.A.,


    Full Text Available The article presents the analysis of the development of the ideas of L.S. Vygotsky’s school using the example of the publications in the international scientific journal “Cultural-Historical Psychology” (for the period 2005 through 2016. Over the period from 2005 to the end of 2016, 595 articles of 524 authors from 32 countries have been published in the journal “Cultural-Historical Psychology.” The study of the subjects of the articles published in the journal was held within the framework of the following criteria: scientometric publication indicators; group of authors; themes of the publications; relevance of the articles for their readers. The research uses the following sources: Russian Science Citation Index (RSCI; repository data of the psychological editions of; report data on the activities of the journal “Cultural-Historical Psychology.” The citation frequency of the journal’s publications peaks in 2007, 2009 and 2006. Empirical findings comprise major part of the publications. The most developed areas are the studies of speech and thinking, personality, and communication.

  16. The Role of L.S. Vygotsky's Ideas in the Development of Social Cognition Paradigm in Modern Psychology: A Review of Foreign Research and Discussion on Perspectives

    Directory of Open Access Journals (Sweden)

    A.B. Kholmogorova


    Full Text Available The author reflects on the reasons for the increased interest of modern foreign social cognition researchers in L.S. Vygotsky's cultural-historical theory in the light of the existing methodological contradictions and recent empirical data. The paper analyzes the main ideas and concepts of cultural-historical theory that were incorporated in research by Vygotsky's foreign followers, including such prominent experts in the field of social cognition as M. Tomasello and Ch. Fernyhough. It describes the conceptual apparatus and models of development of social cognition in phylo-, anthropo- and ontogenesis proposed by these researchers basing on the ideas of cultural-historical approach. The author especially stresses the importance of the idea of the dialogical nature of human thinking as the foundation for social cognition development in ontogenesis. Also reviewed are the mechanisms underlying the emergence of dialogical thinking from egocentric speech that are described in Ch. Fernyhough's model of social cognition development in ontogenesis. The paper concludes with an analysis of the concepts of cultural-historical theory and its current developments by Russian researchers that are of high heuristic potential for the future development of the paradigm of social cognition

  17. Study of the following decays: K{sub l,s} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -}; Etude des desintegrations K{sub l,s} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -}

    Energy Technology Data Exchange (ETDEWEB)

    Cogan, J


    The study of the K{sub L,S} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -} decay modes in the NA48 experiment at CERN is presented in this thesis. Using the full data samples collected in 1998 and 1999, 1285 {+-} 37 events K{sub L} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -} have been extracted over a background of 41 events. The measured branching ratio is: BR(K{sub L} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -})=[3,16{+-}0,09(stat.){+-}0,16(syst.)] x 10{sup -7}. Concerning the K{sub S} mode, a signal of 768 {+-} 28 candidates has been observed over a negligible background. The obtained branching ratio is: BR(K{sub S} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -})=[4,28{+-}0,18(stat.){+-}0,26(syst.)] x 10{sup -5}. Both results are in very good agreement with the values predicted by phenomenological models where the processes K{sub L,S} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -} are described in terms of inner Bremsstrahlung and direct emission contributions. In the K{sub L} mode, the presence of two components with opposed CP states leads to a large asymmetry A in the distribution of the angle {phi} between the decay planes of the two pions and the two electrons. The detailed analysis of the K{sub L} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -} mode ends up to a non-zero value of the asymmetry with more than 4 standard deviations: A(K{sub L} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -})=[13,8{+-}2,8(stat.){+-}2,3(syst.)]%. This result is a clear manifestation of CP violation in this channel. The large value of this asymmetry, in excellent agreement with theoretical prediction, accounts for CP violation in the K{sup 0}-K-bar{sup 0} mixing. Furthermore, it was verified that in the K{sub S} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -} mode which is dominated by the inner Bremsstrahlung component, the asymmetry is compatible with zero: A(K{sub S} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -})=[-0,8{+-}3,6(stat.){+-}1,2(syst.)]%. (author)

  18. Liposomes as nanomedical devices. (United States)

    Bozzuto, Giuseppina; Molinari, Agnese


    Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the "first-generation" liposomes, and liposome-based drugs on the market and in clinical trials.

  19. L-S靶向超声造影微泡淋巴结造影的实验研究%Effectiveness of Lymphography Enhanced by L-S Guide Targeted Microbubbles

    Institute of Scientific and Technical Information of China (English)

    肖雁冰; 赵敏; 高毅


    Objective To explore the effectiveness of lymphography using self-made L-S (lymph selectin) guide targeted microbubbles. Methods Small tissues of VX2 squamous cell carcinoma were implanted into the bilateral vulva of five female rabbits to prepare the animal model of vulval squamous cell carcinoma (VSCC) and inguinal lymph node metastasis in rabbits . L-S guide targeted microbubbles(0. 3 ml/kg) were bolus injected into rabbits by the ear vein in group A, the normal lipid microbubbles(0. 3 ml/kg) were injected in the same way 1 hour after. All the processes were the same as those in group A except the injection order of the two microbubbles were reversed in group B. The effectiveness of lymphography in rabbits which enhanced by two kind of microbubbles were detected by low mechanical index ultrasound device, the imaging features were recorded and analyzed. Results Significant increased high-echo in whole lymph nodes which deduced by L-S guide targeted microbubbles were observed in two groups, the grayscale value of lymphography in group A and group B were 97. 18±8. 38 dB and 92. 36±9. 45 dB respectively, while the features of lymphography caused by normal lipid microbubbles reflected as enhanced-echo in the bordering area of lymph nodes, the grayscale value of lymphography in group A and group B were 83.12±2. 81 dB and 80. 27±3. 56 dB respectively. The difference of grayscale value of lymphography between L-S microbubbles and lipid microbubbles were significant(P<0. 05). Conclusions L-S guide targeted microbubbles possess significant effectiveness of enhancing lymphography, and this features worth further investigation.%目的 探讨自制L-S (lymph-selectin)靶向微泡用于淋巴结造影的效果.方法 雌性兔5只外阴埋置VX2鳞癌组织块制作兔外阴鳞癌及腹股沟转移淋巴结动物模型.A组先经兔耳缘静脉注入L-S靶向微泡(0.3 ml/kg),1h后再注入普通脂质微泡(0.3ml/kg);B组相反.以低机械指数超声检测两组中L-S靶向微泡和普通脂质微泡对腹股沟转移淋巴结的造影效果并进行对比分析.结果 L-S靶向微泡淋巴结造影表现为淋巴结整体回声明显增强,其灰阶值在A、B两组分别为:(97.18±8.38) dB和(92.36±9.45) dB;普通脂质微泡淋巴造影主要表现为淋巴结边缘部位回声增强,其灰阶值在A、B两组分别为:(83.12±2.81) dB和(80.27±3.56) dB.两组中,L-S靶向微泡与普通脂质微泡淋巴结造影的灰阶值比较,差异具有显著性(P<0.05).结论 L-S靶向微泡具有明显增强淋巴结显影的作用.

  20. Liposomal paclitaxel formulations. (United States)

    Koudelka, Stěpán; Turánek, Jaroslav


    Over the past three decades, taxanes represent one of the most important new classes of drugs approved in oncology. Paclitaxel (PTX), the prototype of this class, is an anti-cancer drug approved for the treatment of breast and ovarian cancer. However, notwithstanding a suitable premedication, present-day chemotherapy employing a commercial preparation of PTX (Taxol®) is associated with serious side effects and hypersensitivity reactions. Liposomes represent advanced and versatile delivery systems for drugs. Generally, both in vivo mice tumor models and human clinical trials demonstrated that liposomal PTX formulations significantly increase a maximum tolerated dose (MTD) of PTX which outperform that for Taxol®. Liposomal PTX formulations are in various stages of clinical trials. LEP-ETU (NeoPharm) and EndoTAG®-1 (Medigene) have reached the phase II of the clinical trials; Lipusu® (Luye Pharma Group) has already been commercialized. Present achievements in the preparation of various liposomal formulations of PTX, the development of targeted liposomal PTX systems and the progress in clinical testing of liposomal PTX are discussed in this review summarizing about 30 years of liposomal PTX development.

  1. Ligation Strategies for Targeting Liposomal Nanocarriers

    NARCIS (Netherlands)

    Marques-Gallego, Patricia|info:eu-repo/dai/nl/321769554; de Kroon, Anton I. P. M.|info:eu-repo/dai/nl/084765283


    Liposomes have been exploited for pharmaceutical purposes, including diagnostic imaging and drug and gene delivery. The versatility of liposomes as drug carriers has been demonstrated by a variety of clinically approved formulations. Since liposomes were first reported, research of liposomal


    Directory of Open Access Journals (Sweden)

    Sipai Altaf Bhai. M


    Full Text Available Drug development technologies constituting innovations at the formulation end in the Pharmaceutical industry has received a lot of attention in past two decades. Drug delivery as an opportunity to extend product life cycles has indeed proved its place in the market with significant advantages of therapeutic gains as well as commercial success. Carrier technology offers an intelligent approach for drug delivery by coupling the drug to a carrier particle such as liposomes, microspheres, nanoparticles, etc. which modulates the release and absorption characteristics of the drug. Liposomes are well known to alter the bio distribution of entrapped substances by protecting the enclosed material. They are widely used as vehicles to target the specific molecule to specific organ. During the last few decades liposomes have attracted great interest as ideal models for biological membranes as well as efficient carriers for drugs, diagnostics, vaccines, nutrients and other bioactive agents. Many techniques and methodologies have involved for the manufacture of liposomes, on small and large scales, since their introduction to the scientific community around 40 years ago. This article intends to provide an overview of the advantages and disadvantages of liposome preparation methods,their stability, bio distribution and their uses as drug delivery systems. The conventional method of preparing liposomes is basically for the multilamellar vesicles (MLVs. However, other methods are used to reduce the size of these MLVs to small unilamellar vesicles (SUVs so as to increase their plasma lifetime and consequently increase the possibility of achieving greater tissue localisation. Some of these methods of size reduction are sonication and high pressure extrusion. Each of these methods has its own advantages and disadvantages. Large unilamellar vesicles (LUVs, on the other hand, are prepared mainly by detergent removal method and reverse phase extrusion technique. There

  3. Temoporfin-loaded liposomes

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Freisleben, Ines; Steiniger, Frank


    Temoporfin (mTHPC) is a potent but highly hydrophobic second-generation photosensitizer and has been approved for the palliative treatment of patients with advanced head and neck cancer by photodynamic therapy. Liposome formulations have been evaluated as carrier system for this drug to overcome...... some problems associated with the commercial formulation Foscan where the drug is dissolved in a mixture of water-free ethanol and propylene glycol. The present study focuses on the physicochemical characterization of different liposome formulations with special emphasis on the influence of drug...

  4. 一种L/S波段双频双圆极化缝隙天线的设计实现%Design and Implementation Circularly Polarized Slot of Dual-Frequency Dual Antenna for L/S Band

    Institute of Scientific and Technical Information of China (English)

    吴锟; 屈德新; 胡永金


    文章设计了一种用于实现L波段圆极化的平面缝隙天线,并在此天线的基础上,通过添加寄生贴片,实现L/S波段双频双圆极化的性能。该天线通过一条矩形缝隙将圆环形天线切断,调节缝隙的宽度和角度,实现了圆极化辐射,通过背面的矩形条带对天线激励,使得天线的阻抗得以较好地匹配。在此基础上,又在天线上方加一圆形寄生贴片,通过互耦作用,分别实现了在1.39GHz-1.48GHz和2.60GHz-2.66GHz两个频段不同旋向的圆极化辐射,同时将矩形条带馈线调整为十字形,改善了阻抗带宽。借助于仿真软件对天线参数进行优化,并在此基础上制作了实物。测试结果表明,该设计达到了仿真的效果。%A dual-frequency circularly polarized slot antenna for L-band was designed. Based on this, the proposed antenna realizes dual circularly polarized radiations at L/S by loading a par- asitic patch. The antenna is composed of an annular with a rectangular slot. By adjusting the size and the angle of the slot, the circular polarization was achieved. The bandwidth matches well with the rectangular feed-line. And then a circular parasitic patch was put above the antenna. As the mutual-coupling of the two patches, the proposed antenna realizes dual circularly polarized radiations at 1.39-1.48 GHz and 2.60-2. 66 GHz. For designing the cross feeding strip, the impedance bandwidth is better. The parameters of the antenna were optimized by the simulation software, and the antenna was manufactured. The measure result meets the simulation.

  5. Boronated liposome development and evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Hawthorne, M.F. [Univ. of California, Los Angeles, CA (United States)


    The boronated liposome development and evaluation effort consists of two separate tasks. The first is the development of new boron compounds and the synthesis of known boron species with BNCT potential. These compounds are then encapsulated within liposomes for the second task, biodistribution testing in tumor-bearing mice, which examines the potential for the liposomes and their contents to concentrate boron in cancerous tissues.

  6. A Remote Controlled Valve in Liposomes for Triggered Liposomal Release

    NARCIS (Netherlands)

    Koçer, Armağan


    In order to reduce the toxicity and increase the efficacy of drugs, there is a need for smart drug delivery systems. Liposomes are one of the promising tools for this purpose. An ideal liposomal delivery system should be stable, long-circulating, accumulate at the target site and release its drug in

  7. Biological activity of liposomal vanillin. (United States)

    Castan, Leniher; Del Toro, Grisel; Fernández, Adolfo A; González, Manuel; Ortíz, Emilia; Lobo, Daliana


    This article presents a study of vanillin encapsulation inside multilamellar liposomes, with emphasis on the evaluation of antioxidant activity, the hemolytic effect, and the antisickling properties of these products. Egg phosphatidylcholine-cholesterol and egg phosphatidylcholine-cholesterol-1-O-decylglycerol liposomes were prepared by mechanical dispersion, all with vanillin included. Vesicles were characterized by determination of encapsulation efficiency and vanillin retention capacity. Antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The hemolytic effect of liposomes was also evaluated by spectrophotometry, as well as the antisickling activity by the Huck test using optical microscopy. Results showed that the lipid composition of liposomes did not significantly affect the encapsulation efficiency. Stable vesicles were obtained with a high retention percentage of vanillin. Liposomes exhibited a high capture of the DPPH radical compared to free vanillin and 1-O-decylglycerol (C10) in solution. Vesicles caused no significant hemolisys in normal erythrocytes, nor in those coming from patients with sickle cell anemia. Vanillin encapsulated in liposomes retained its antisickling activity, with a greater effect for C10-containing vesicles. Our results show that vanillin encapsulation in liposomes is a way to enhance the pharmacologic properties of this molecule using a suitable vehicle.

  8. Phospholipid liposomes functionalized by protein (United States)

    Glukhova, O. E.; Savostyanov, G. V.; Grishina, O. A.


    Finding new ways to deliver neurotrophic drugs to the brain in newborns is one of the contemporary problems of medicine and pharmaceutical industry. Modern researches in this field indicate the promising prospects of supramolecular transport systems for targeted drug delivery to the brain which can overcome the blood-brain barrier (BBB). Thus, the solution of this problem is actual not only for medicine, but also for society as a whole because it determines the health of future generations. Phospholipid liposomes due to combination of lipo- and hydrophilic properties are considered as the main future objects in medicine for drug delivery through the BBB as well as increasing their bioavailability and toxicity. Liposomes functionalized by various proteins were used as transport systems for ease of liposomes use. Designing of modification oligosaccharide of liposomes surface is promising in the last decade because it enables the delivery of liposomes to specific receptor of human cells by selecting ligand and it is widely used in pharmacology for the treatment of several diseases. The purpose of this work is creation of a coarse-grained model of bilayer of phospholipid liposomes, functionalized by specific to the structural elements of the BBB proteins, as well as prediction of the most favorable orientation and position of the molecules in the generated complex by methods of molecular docking for the formation of the structure. Investigation of activity of the ligand molecule to protein receptor of human cells by the methods of molecular dynamics was carried out.


    Directory of Open Access Journals (Sweden)

    Romanova OA


    Full Text Available Introduction. With the transport links development there is rather important issue respiratory viral infections spread, especially influenza. The only method controlling influenza is vaccination. Search and development effective and safe vaccines is important. Material and methods. In base SO "Mechnikov Institute Microbiology and Immunology National Ukrainian Academy Medical Sciences" in the scientific theme "Developing new approaches to creating viral vaccines and study specific activity depending of type and degree component`s modification" was created several experimental influenza vaccine with subsequent component`s modification for selecting the most optimal pattern of safety and immunogenicity. In assessing the influenza vaccine safety is using a few criteria, including, reactivity, as measured by the frequency of local and systemic adverse (negative effects, which due to its introduction, and for lipid content drugs, ability to influence oxidation processes. At present study phase was determined: a systemic reaction and local reaction of delayed-type hypersensitivity (foot pad swelling assay;b lipids and proteins peroxidation processes after administration officinal and experimental vaccines (content protein’s carbonyl groups, lipid’s hydroperoxides, activity of glutathione-peroxidase.Study objects were trivalent seasonal influenza vaccine, "Vaxigrip" (Sanofi Pasteur, S.A., France, "Inflexal V" (Biotech Ltd. Berne, Switzerland and experimental vaccine samples. Highest immunogenicity vaccines had undergone improvements and modifications using adjuvant systems and acylation influenza proteins. Liposomes 2 – the experimental influenza vaccine with a liposome negative charge and antigenic composition like split vaccines "Vaksihryp". Liposomes 2.1 - the adjuvantexperimental influenza vaccine with modifications liposomal components (etoniy and chlorophyllipt molecules embedded in liposomal membrane. Liposomes 2.2 - the adjuvant

  10. Recognition of Biotin-functionalized Liposomes

    Institute of Scientific and Technical Information of China (English)

    Hai Feng ZHU; Jun Bai LI


    Functionalized liposomes were prepared by mixing the biotin in the lipid vesicle suspensions. The experiments through immersing streptavidin deposited mica into the biotin modified liposome solution testify the specifically biological binding interaction and extend the function of liposomes as a biosensor or drug carrier.

  11. Cardiac safety of liposomal anthracyclines. (United States)

    Ewer, Michael S; Martin, Francis J; Henderson, Craig; Shapiro, Charles L; Benjamin, Robert S; Gabizon, Alberto A


    Conventional anthracyclines are active against many tumor types, but cardiotoxicity related to the cumulative dose may limit their use; this is particularly problematic for patients with risk factors for increased toxicity, for those who have received any anthracycline in the past, or for those who are to receive other cardiotoxic agents. Preclinical studies determined that encapsulating conventional anthracyclines in liposomes reduced the incidence and severity of cumulative dose-related cardiomyopathy while preserving antitumor activity. In controlled clinical trials, the risk of cardiotoxicity was significantly lower when nonpegylated liposomal doxorubicin (Myocet [NPLD]) was substituted for conventional doxorubicin, but the risk was not significantly different when NPLD was used in place of conventional epirubicin. Direct comparisons to conventional doxorubicin therapy showed comparable efficacy but significantly lower risk of cardiotoxicity with pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]) therapy. Retrospective and prospective trials have not identified a maximum "cardiac safe" dose of PLD, despite use of cumulative doses exceeding 2,000 mg/m2 in some patients. Liposomal daunorubicin (DaunoXome [DNX]) may be associated with a lower risk of cardiotoxicity than conventional anthracyclines, but comparative trials are not available. With respect to combination chemotherapy, early results of clinical trials suggest that combining trastuzumab or a taxane with NPLD or PLD instead of a conventional anthracycline significantly reduces cardiotoxicity risk without reducing chemotherapeutic efficacy. Further results are eagerly awaited from ongoing controlled trials of cardiac safety with long-term liposomal anthracycline therapy, either alone or in combination with other potentially cardiotoxic agents.

  12. [Liposomal amphotericin B]. (United States)

    Fukasawa, Masatomo


    Liposomal amphotericin B (AmBisome) is a DDS (drug delivery system) formulation of amphotericin B (AMPH-B), and has been developed in an attempt to reduce the toxicity of AMPH-B while retaining its therapeutic efficacy. AMPH-B has been the "gold standard" of antifungal therapy over the past four decades. It has a broad spectrum of fungicidal activity against a number of clinically important pathogens including Aspergillus and Candida. The mechanism of action of AMPH-B involves binding to ergosterol, the principal sterol in fungal cell membranes. Binding to ergosterol causes an increase in fungal membrane permeability, electrolyte leakage, and cell death. AMPH-B has affinity for cholesterol in mammalian membranes, which leads to severe side-effects including kidney damage. AmBisome is a unilamellar vesicle composed of AMPH-B and phospholipid. Upon administration, AmBisome remains intact in the blood and distributes to the tissues where fungal infection may occur, and is disrupted after attachment to the outside of fungal cells, resulting in fungal cell death. AmBisome and AMPH-B show similar in vitro and in vivo antifungal activity and clinical efficacy. However, AmBisome has less infusion-related toxicity and nephrotoxicity than AMPH-B.

  13. DNA controlled assembly of liposomes

    DEFF Research Database (Denmark)

    Vogel, Stefan; Jakobsen, Ulla; Simonsen, Adam Cohen


    DNA-encoding of solid nanoparticles requires surfacechemistry, which is often tedious and not generally applicable. In the present study non-covalently attached DNA are used to assemble soft nanoparticles (liposomes) in solution. This process displays remarkably sharp thermal transitions from...

  14. Liposomal bupivacaine and clinical outcomes. (United States)

    Tong, Yi Cai Isaac; Kaye, Alan David; Urman, Richard D


    In the multimodal approach to the management of postoperative pain, local infiltration and regional blocks have been increasingly utilized for pain control. One of the limitations of local anesthetics in the postoperative setting is its relatively short duration of action. Multivesicular liposomes containing bupivacaine have been increasingly utilized for their increased duration of action. Compared with bupivacaine HCl, local infiltration of liposomal bupivacaine has shown to have an increase in duration of action and causes delay in peak plasma concentration. In this article, we attempt to review the clinical literature surrounding liposomal bupivacaine and its evolving role in perioperative analgesia. This new bupivacaine formation may have promising implications in postoperative pain control, resulting in increased patient satisfaction and a decrease in both hospital stay and opioid-induced adverse events (AEs). Although more studies are needed, the preliminary clinical trials suggest that liposomal bupivacaine has predictable pharmacokinetics, a similar side effect profile compared with bupivacaine HCl, and is effective in providing increased postoperative pain control.

  15. Capacious and programmable multi-liposomal carriers (United States)

    Yaroslavov, Alexander A.; Sybachin, Andrey V.; Zaborova, Olga V.; Migulin, Vasiliy A.; Samoshin, Vyacheslav V.; Ballauff, Matthias; Kesselman, Ellina; Schmidt, Judith; Talmon, Yeshayahu; Menger, Fredric M.


    Spherical polycationic brushes (SPBs) were synthesized by grafting polycationic chains onto 100 nm polystyrene particles. These particles were exposed to unilamellar egg-lecithin (EL) liposomes with a mean diameter of 40 nm that had been rendered anionic via the presence of 10 molar% of phosphatidylserine (PS1-). The liposomes also contained 30 mole% of a morpholinocyclohexanol-based lipid (MOCH) that undergoes a conformational flip when the pH is decreased from 7.0 to 5.0. Mixtures of SPBs and liposomes at pH 7 gave an electrostatically-driven complex possessing, on average, about 40 liposomes for each SPB particle. It was found that the bound liposomes rapidly release much of their contents when the pH is reduced from 7.0 to 5.0 owing mostly to a MOCH conformational change that creates defects in the bilayer membrane. The drop in pH does not, however, induce a separation of the liposomes from the SPBs. Around 50-60% of the liposome contents escape before, it is reasoned, lateral and transmembrane motion of the membrane components heals the defects and prevents further release. Remarkably, the liposomes complexed with SPB release their cargo much faster than the identical but non-complexed liposomes.Spherical polycationic brushes (SPBs) were synthesized by grafting polycationic chains onto 100 nm polystyrene particles. These particles were exposed to unilamellar egg-lecithin (EL) liposomes with a mean diameter of 40 nm that had been rendered anionic via the presence of 10 molar% of phosphatidylserine (PS1-). The liposomes also contained 30 mole% of a morpholinocyclohexanol-based lipid (MOCH) that undergoes a conformational flip when the pH is decreased from 7.0 to 5.0. Mixtures of SPBs and liposomes at pH 7 gave an electrostatically-driven complex possessing, on average, about 40 liposomes for each SPB particle. It was found that the bound liposomes rapidly release much of their contents when the pH is reduced from 7.0 to 5.0 owing mostly to a MOCH conformational

  16. Lipophilic DNA-conjugates: DNA controlled assembly of liposomes

    DEFF Research Database (Denmark)

    Vogel, Stefan; Jakobsen, Ulla


    liposomes. The process results in large liposome aggregates with dramatically different optical properties compared to individual liposomes in solution. The presented method enables fast and easy detection of target polynucleotides. Furthermore, the system displays remarkably sharp thermal transitions which...

  17. The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes

    DEFF Research Database (Denmark)

    Korsholm, Karen Smith; Agger, Else Marie; Foged, Camilla


    Cationic liposomes are being used increasingly as efficient adjuvants for subunit vaccines but their precise mechanism of action is still unknown. Here, we investigated the adjuvant mechanism of cationic liposomes based on the synthetic amphiphile dimethyldioctadecylammonium (DDA). The liposomes...... concentrations. This efficient adsorption onto the liposomes led to an enhanced uptake of OVA by BM-DCs as assessed by flow cytometry and confocal fluorescence laser-scanning microscopy. This was an active process, which was arrested at 4 degrees and by an inhibitor of actin-dependent endocytosis, cytochalasin D....... In vivo studies confirmed the observed effect because adsorption of OVA onto DDA liposomes enhanced the uptake of the antigen by peritoneal exudate cells after intraperitoneal injection. The liposomes targeted antigen preferentially to antigen-presenting cells because we only observed a minimal uptake...

  18. Liposomal Indocyanine Green for Enhanced Photothermal Therapy. (United States)

    Yoon, Hwan-Jun; Lee, Hye-Seong; Lim, Ji-Young; Park, Ji-Ho


    In this study, we engineered liposomal indocyanine green (ICG) to maximize its photothermal effects while maintaining the fluorescence intensity. Various liposomal formulations of ICG were prepared by varying the lipid composition and the molar ratio between total lipid and ICG, and their photothermal characteristics were evaluated under near-infrared irradiation. We showed that the ICG dispersity in the liposomal membrane and its physical interaction with phospholipids were the main factors determining the photothermal conversion efficiency. In phototherapeutic studies, the optimized formulation of liposomal ICG showed greater anticancer effects in a mouse tumor model compared with other liposomal formulations and the free form of ICG. Furthermore, we utilized liposomal ICG to visualize the metastatic lymph node around the primary tumor under fluorescence imaging guidance and ablate the lymph node with the enhanced photothermal effect, indicating the potential for selective treatment of metastatic lymph node.

  19. Evaluation of Extrusion Technique for Nanosizing Liposomes

    Directory of Open Access Journals (Sweden)

    Sandy Gim Ming Ong


    Full Text Available The aim of the present study was to study the efficiency of different techniques used for nanosizing liposomes. Further, the aim was also to evaluate the effect of process parameters of extrusion techniques used for nanosizing liposomes on the size and size distribution of the resultant liposomes. To compare the efficiency of different nanosizing techniques, the following techniques were used to nanosize the liposomes: extrusion, ultrasonication, freeze-thaw sonication (FTS, sonication and homogenization. The extrusion technique was found to be the most efficient, followed by FTS, ultrasonication, sonication and homogenization. The extruder used in the present study was fabricated using readily available and relatively inexpensive apparatus. Process parameters were varied in extrusion technique to study their effect on the size and size distribution of extruded liposomes. The results obtained indicated that increase in the flow rate of the extrusion process decreased the size of extruded liposomes however the size homogeneity was negatively impacted. Furthermore, the liposome size and distribution was found to decline with decreasing membrane pore size. It was found that by extruding through a filter with a pore size of 0.2 µm and above, the liposomes produced were smaller than the pore size, whereas, when they were extruded through a filter with a pore size of less than 0.2 µm the resultant liposomes were slightly bigger than the nominal pore size. Besides that, increment of extrusion temperature above transition temperature of the pro-liposome had no effect on the size and size distribution of the extruded liposomes. In conclusion, the extrusion technique was reproducible and effective among all the methods evaluated. Furthermore, processing parameters used in extrusion technique would affect the size and size distribution of liposomes. Therefore, the process parameters need to be optimized to obtain a desirable size range and homogeneity

  20. Tumor targeting using liposomal antineoplastic drugs (United States)

    Huwyler, Jörg; Drewe, Jürgen; Krähenbühl, Stephan


    During the last years, liposomes (microparticulate phospholipid vesicles) have been used with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumor drugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vector-conjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this field of research. PMID:18488413

  1. Liposomal cancer therapy: exploiting tumor characteristics

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars


    of cancer treatments. In the search for more effective cancer treatments, nanoparticle- based drug delivery systems, such as liposomes, that are capable of delivering their drug payload selectively to cancer cells are among the most promising approaches. Areas covered in this review: This review provides...... of new liposomal drug delivery systems that better exploit tumor characteristic features is likely to result in more efficacious cancer treatments....... an overview of current strategies for improving the different stages of liposomal cancer therapy, which involve transporting drug-loaded liposomes through the bloodstream, increasing tumor accumulation, and improving drug release and cancer cell uptake after accumulation at the tumor target site. What...

  2. Liposomal drug delivery systems--clinical applications. (United States)

    Goyal, Parveen; Goyal, Kumud; Vijaya Kumar, Sengodan Gurusamy; Singh, Ajit; Katare, Om Prakash; Mishra, Dina Nath


    Liposomes have been widely investigated since 1970 as drug carriers for improving the delivery of therapeutic agents to specific sites in the body. As a result, numerous improvements have been made, thus making this technology potentially useful for the treatment of certain diseases in the clinics. The success of liposomes as drug carriers has been reflected in a number of liposome-based formulations, which are commercially available or are currently undergoing clinical trials. The current pharmaceutical preparations of liposome-based therapeutic systems mainly result from our understanding of lipid-drug interactions and liposome disposition mechanisms. The insight gained from clinical use of liposome drug delivery systems can now be integrated to design liposomes that can be targeted on tissues, cells or intracellular compartments with or without expression of target recognition molecules on liposome membranes. This review is mainly focused on the diseases that have attracted most attention with respect to liposomal drug delivery and have therefore yielded most progress, namely cancer, antibacterial and antifungal disorders. In addition, increased gene transfer efficiencies could be obtained by appropriate selection of the gene transfer vector and mode of delivery.

  3. Interactions of liposomes with dental restorative materials. (United States)

    Nguyen, Sanko; Adamczak, Malgorzata; Hiorth, Marianne; Smistad, Gro; Kopperud, Hilde Molvig


    The in vitro adsorption and retention of liposomes onto four common types of dental restorative materials (conventional and silorane-based resin composites as well as conventional and resin-modified glass ionomer cements (GIC)) have been investigated due to their potential use in the oral cavity. Uncoated liposomes (positively and negatively charged) and pectin (low- and high-methoxylated) coated liposomes were prepared and characterized in terms of particle size and zeta potential. The adsorption of liposomes was performed by immersion, quantified by fluorescence detection, and visualized by fluorescence imaging and atomic force microscopy. Positive liposomes demonstrated the highest adsorption on all four types of materials likely due to their attractive surface charge. They also retained well (minimum 40% after 60 min) on both conventional resin composite and GIC even when exposed to simulated salivary flow. Although an intermediate initial level of adsorption was found for the pectin coated liposomes, at least 70% high methoxylated-pectin coated liposomes still remained on the conventional resin composite after 60 min flow exposure. This indicates significant contribution of hydrophobic interactions in the prolonged binding of liposomes to resin composites. Based on these results, the present paper suggests two new possible applications of liposomes in the preservation of dental restorations.

  4. Lysolipid containing liposomes for transendothelial drug delivery

    Directory of Open Access Journals (Sweden)

    Koklic Tilen


    Full Text Available Abstract Background Designing efficient 'vectors', to deliver therapeutics across endothelial barriers, in a controlled manner, remains one of the key goals of drug development. Recently, transcytosis of liposome encapsulated fluorescence marker calcein across a tight cell barrier was studied. The most efficient liposomes were found to be liposomes containing sufficient amount of alkyl phospholipid (APL perifosine. APLs have similar structure as lysophosphatidyl choline (LPC, since APLs were synthesized as metabolically stable analogues of LPC, which increases endothelial permeability directly by inducing endothelial cell contraction, resulting in formation of gaps between endothelial cells. Since one of the unique properties of lysolipid, containing liposomal formulations is dynamic equilibrium of lysolipids, which are distributed among liposomes, micelles, and free form, such liposomes represent a reservoir of free lysolipids. On the other hand lysolipid containing liposomes also represent a reservoir of an encapsulated hydrophilic drug. Presentation of the hypothesis We hypothesize that free lysolipids, with highest concentration in vicinity of drug carrying liposomes, compromise endothelial integrity, primarily where concentrations of liposomes is the highest, in a similar manner as LPC, by formation of gaps between endothelial cells. Liposome encapsulated drug, which leaks from liposomes, due to liposome destabilization, caused by lysolipid depletion, can therefore be efficiently transported across the locally compromised endothelial barrier. Testing the hypothesis This hypothesis could be verified: by measuring binding of perifosine and other lysolipids to albumin and to lysophospholipid receptor (LPL-R group; formation of stress fibers and subsequent cell contraction; activation of RhoA, and endothelial barrier dysfunction; by a synthesis of other LPC analogues with high critical micellar concentration and measuring their effect on

  5. Liposome adhesion generates traction stress (United States)

    Murrell, Michael P.; Voituriez, Raphaël; Joanny, Jean-François; Nassoy, Pierre; Sykes, Cécile; Gardel, Margaret L.


    Mechanical forces generated by cells modulate global shape changes required for essential life processes, such as polarization, division and spreading. Although the contribution of the cytoskeleton to cellular force generation is widely recognized, the role of the membrane is considered to be restricted to passively transmitting forces. Therefore, the mechanisms by which the membrane can directly contribute to cell tension are overlooked and poorly understood. To address this, we directly measure the stresses generated during liposome adhesion. We find that liposome spreading generates large traction stresses on compliant substrates. These stresses can be understood as the equilibration of internal, hydrostatic pressures generated by the enhanced membrane tension built up during adhesion. These results underscore the role of membranes in the generation of mechanical stresses on cellular length scales and that the modulation of hydrostatic pressure due to membrane tension and adhesion can be channelled to perform mechanical work on the environment.

  6. DNA controlled assembly of liposomes

    DEFF Research Database (Denmark)

    Vogel, Stefan; Jakobsen, Ulla; Simonsen, Adam Cohen


    DNA-encoding of solid nanoparticles requires surfacechemistry, which is often tedious and not generally applicable. In the present study non-covalently attached DNA are used to assemble soft nanoparticles (liposomes) in solution. This process displays remarkably sharp thermal transitions from...... assembled to disassembled state for which reason this method allows easy and fast detection of polynucleotides (e.g. DNA or RNA), including single nucleotide polymorphisms as well as insertions and deletions....

  7. Liposomal formulations of cytotoxic drugs. (United States)

    Janknegt, R


    Liposomes are microscopic particles of lipid bilayer membrane that enclose aqueous internal compartments. These drug-delivery systems offer a very interesting opportunity for delivering cytotoxic drugs with equal or improved clinical efficacy and reduced toxicity. The most important clinical application of liposomes until now has been the inclusion of amphotericin B. At the same dose level, liposomal amphotericin B is as effective or slightly less effective than the conventional formulation, but much higher dosages, up to 5-7 mg kg-1day-1, can be given with acceptable toxicity. There are three preparations of cytotoxic drugs in an advanced stage of commercial development. Two of these (Doxil and TLD D99) contain doxorubicin and the other (DaunoXome) contains daunorubicin. The cardiac toxicity of the three preparations under clinical evaluation appears to be low in comparison with conventional doxorubicin or daunorubicin. No direct comparisons between the new formulations are available, so it is not yet possible to make any statements concerning their relative efficacy and toxicity. DaunoXome is the only drug that is approved in any country, and is also the best documented. It is too early to make recommendations concerning the place of these drugs in therapy. The marked increase in concentrations at the site of the tumour has yet to lead to increased therapeutic efficacy. These findings need further investigation. The efficacy of liposomal preparations in Kaposi's sarcoma appears to be similar to that of standard therapy and the clinical tolerance is good. Perhaps combination therapy with other cytotoxic agents could result in improved clinical efficacy. Their cost will probably be high in comparison with standard therapies.

  8. ¿Derechos vs. derechos?: Los derechos de l@s niñ@s alojados en el sistema carcelario. Relación con la pobreza y la exclusión social Rights vs. Rights?: The Rights of Children Living in Jail. The Relation with Poverty and Social Exclusion

    Directory of Open Access Journals (Sweden)

    Valeria Pérez Chaca


    Full Text Available La historia de la infancia en el mundo, y en particular en América Latina, cuenta con aristas diversas y complejas que de un modo u otro develan un modelo de sociedad que se ha ido construyendo a lo largo de los tiempos. En este sentido, han sido numerosos los esfuerzos para lograr una legislación que regule y garantice los derechos de l@s niñ@s y que obligue a los Estados a activar mecanismos adecuados para su protección. Pero la realidad de l@s niñ@s que se encuentran alojados junto a sus madres en las cárceles argentinas aún requiere de un fuerte debate, tanto en los ámbitos públicos como académicos. A partir de esto es que nos proponemos plantear la discusión, intentando arrojar algunos elementos para el debate desde el enfoque de los derechos humanos. Para ello, y a partir de una recorrida por la historia y los antecedentes en la temática, nos interrogamos acerca de las posibles alternativas frente a una realidad compleja que nos interpela día a día.The history of childhood in the world, and particularly in Latin America, has divers and complex edges which, in one way or another, show a model of society which has been constructed during a long period of time. They have been numerous the efforts to obtain a legislation which regulates and guarantees the rights of the kids and which require the State to activate the adequate mechanisms to protect them. Actually, children are accommodated in Argentinean prisons with their mothers, and this fact is still to be discussed on public and academic milieus. It is from this point of view that we have the intention to set this discussion out, trying to contribute to the debate from a Human Rights perspective. With this aim, reconstructing the history and taking into account the available information, we start to pose the question about the possible alternatives against a difficult reality which we have to face daily.

  9. Radioprotective effect of transferrin targeted citicoline liposomes. (United States)

    Suresh Reddy, Jannapally; Venkateswarlu, Vobalaboina; Koning, Gerben A


    The high level of expression of transferrin receptors (Tf-R) on the surface of endothelial cells of the blood-brain-barrier (BBB) had been widely utilized to deliver drugs to the brain. The primary aim of this study was to use transferrin receptor mediated endocytosis as a pathway for the rational development of holo-transferrin coupled liposomes for drug targeting to the brain. Citicoline is a neuroprotective agent used clinically to treat for instance Parkinson disease, stroke, Alzheimer's disease and brain ischemia. Citicoline does not readily cross the BBB because of its strong polar nature. Hence, citicoline was used as a model drug. (Citicoline liposomes have been prepared using dipalmitoylphosphatidylcholine (DPPC) or distearoylphosphatidylcholine (DSPC) by dry lipid film hydration-extrusion method). The effect of the use of liposomes composed of DPPC or DSPC on their citicoline encapsulation efficiency and their stability in vitro were studied. Transferrin was coupled to liposomes by a technique which involves the prevention of scavenging diferric iron atoms of transferrin. The coupling efficiency of transferrin to the liposomes was studied. In vitro evaluation of transferrin-coupled liposomes was performed for their radioprotective effect in radiation treated cell cultures. In this study, OVCAR-3 cells were used as a model cell type over-expressing the Tf-R and human umbilical vein endothelial cells (HUVEC) as BBB endothelial cell model. The average diameter of DPPC and DSPC liposomes were 138 +/- 6.3 and 79.0 +/- 3.2 nm, respectively. The citicoline encapsulation capacity of DPPC and DSPC liposomes was 81.8 +/- 12.8 and 54.9 +/- 0.04 microg/micromol of phospholipid, respectively. Liposomes prepared from DSPC showed relatively better stability than DPPC liposomes at 37 degrees C and in the presence of serum. Hence, DSPC liposomes were used for transferrin coupling and an average of 46-55 molecules of transferrin were present per liposome. Free citicoline

  10. Nanoparticle Stabilized Liposomes for Acne Therapy (United States)

    Fu, Victoria

    Acne vulgaris is a common skin disease that affects over 40 million people in the United States alone. The main cause of acne vulgaris is Propionibacterium acnes (P. acnes), resides deep in the pores and follicles of the skin in order to feed on oil produced by the sebaceous glands. The liposome is a lipid based nanoparticle with numerous advantages over free drug molecules as an acne treatment alternative. Bare liposomes loaded with lauric acid (LipoLA) were found to show strong antimicrobial activity against P. acnes while generating minimal toxicity. However, the platform is limited by the spontaneous tendency of liposomes to fuse with each other. Attaching nanoparticles to the surface of liposomes can overcome this challenge by providing steric repulsion and reduce surface tension. Thus, carboxyl-functionalized gold nanoparticles (AuC) were attached to the surface of liposomes (AuC-liposomes) loaded with doxycycline, a general tetracycline antibiotic. These particles were found to have a diameter of 120 nm and a zeta potential of 20.0 mV. Both fluorescent and antimicrobial studies demonstrated that based on electrostatic interaction, negatively charged AuC attached to the liposome's positively charged surface and stabilized liposomes in a neutral pH environment (pH = 7.4). Upon entering the skin's acidic environment (pH = 4), AuC detached from the liposome's surface and liposomes could fuse with P. acnes residing in the pores. Furthermore, toxicity studies showed that AuC-liposomes did not induce any significant toxicity, while two of the leading over-the-counter therapies, benzoyl peroxide and salicylic acid, generated substantial skin irritation.

  11. Anomalous freezing behavior of nanoscale liposomes

    DEFF Research Database (Denmark)

    Spangler, E. J.; Kumar, P. B. S.; Laradji, M.


    The effect of the finite size of one-component liposomes on their phase behavior is investigated via simulations of an implicit-solvent model of self-assembled lipid bilayers. We found that the high curvature of nanoscale liposomes has a significant effect on their freezing behavior. While...

  12. Transfer mechanism of temoporfin between liposomal membranes. (United States)

    Hefesha, Hossam; Loew, Stephan; Liu, Xiangli; May, Sylvio; Fahr, Alfred


    The transfer kinetics of temoporfin, a classic photosensitizer, was analyzed by investigating the influence of total lipid content, temperature, as well as charge, acyl chain length, and saturation of the lipids in donor vesicles using a mini ion exchange column technique. The obtained results are consistent with an apparent first order kinetics in which the transfer proceeds through both liposome collisions and through the aqueous phase. We present a corresponding theoretical model that accounts for the detailed distribution of drug molecules in donor and acceptor liposomes and predicts the transfer rates as a function of drug concentration and number of donor and acceptor liposomes. The experimentally observed transfer rates depended strongly on the temperature and comply with the Arrhenius equation. Thermodynamic calculations indicate the transfer process to be entropically controlled. In terms of the charge of donor liposomes, positively charged liposomes showed transfer rates faster than negatively charged liposomes whereas the maximum amount transferred was almost the same. A more rigid structure of the donor liposomes increases the transfer rate of temoporfin, which is caused by expelling the drug from the membrane interior, as proposed in former work. In summary, our combined theoretical/experimental approach offers a systematic way to study the mechanism of drug release from liposome-based delivery systems.

  13. Methods for using redox liposome biosensors (United States)

    Cheng, Quan; Stevens, Raymond C.


    The present invention provides methods and compositions for detecting the presence of biologically-important analytes by using redox liposome biosensors. In particular, the present invention provides liposome/sol-gel electrodes suitable for the detection of a wide variety of organic molecules, including but not limited to bacterial toxins.

  14. The protein corona of circulating PEGylated liposomes. (United States)

    Palchetti, Sara; Colapicchioni, Valentina; Digiacomo, Luca; Caracciolo, Giulio; Pozzi, Daniela; Capriotti, Anna Laura; La Barbera, Giorgia; Laganà, Aldo


    Following systemic administration, liposomes are covered by a 'corona' of proteins, and preserving the surface functionality is challenging. Coating the liposome surface with polyethylene glycol (PEG) is the most widely used anti-opsonization strategy, but it cannot fully preclude protein adsorption. To date, protein binding has been studied following in vitro incubation to predict the fate of liposomes in vivo, while dynamic incubation mimicking in vivo conditions remains largely unexplored. The main aim of this investigation was to determine whether shear stress, produced by physiologically relevant dynamic flow, could influence the liposome-protein corona. The corona of circulating PEGylated liposome was thoroughly compared with that formed by incubation in vitro. Systematic comparison in terms of size, surface charge and quantitative composition was made by dynamic light scattering, microelectrophoresis and nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS). Size of coronas formed under static vs. dynamic incubation did not appreciably differ from each other. On the other side, the corona of circulating liposomes was more negatively charged than its static counterpart. Of note, the variety of protein species in the corona formed in a dynamic flow was significantly wider. Collectively, these results demonstrated that the corona of circulating PEGylated liposomes can be considerably different from that formed in a static fluid. This seems to be a key factor to predict the biological activity of a liposomal formulation in a physiological environment.

  15. Liposome-Encapsulated Hemoglobin for Emergency Resuscitation. (United States)


    have infused liposome -encapsulated amphotericin B to treat patients with systemic fungal infections. Their formulation includes 30% dimyristoyl...procedure, including exploring new industrial-scale methodologies for liposome manufacture. In addition we have focused on basic problems of biophysics...circulation persistance of this new formulation , as produced by the Microfluidizer, is obviously necessary. The influence of negatively-charged lipids on

  16. Liposomal nanocapsules in food science and agriculture. (United States)

    Taylor, T Matthew; Davidson, P Michael; Bruce, Barry D; Weiss, Jochen


    Liposomes, spherical bilayer vesicles from dispersion of polar lipids in aqueous solvents, have been widely studied for their ability to act as drug delivery vehicles by shielding reactive or sensitive compounds prior to release. Liposome entrapment has been shown to stabilize encapsulated, bioactive materials against a range of environmental and chemical changes, including enzymatic and chemical modification, as well as buffering against extreme pH, temperature, and ionic strength changes. Liposomes have been especially useful to researchers in studies of various physiological processes as models of biological membranes in both eukaryotes and prokaryotes. Industrial applications include encapsulation of pharmaceuticals and therapeutics, cosmetics, anti-cancer and gene therapy drugs. In the food industry, liposomes have been used to deliver food flavors and nutrients and more recently have been investigated for their ability to incorporate food antimicrobials that could aid in the protection of food products against growth of spoilage and pathogenic microorganisms. In this review we briefly introduce key physicochemical properties of liposomes and review competing methods for liposome production. A survey of non-agricultural and food applications of liposomes are given. Finally, a detailed up-to-date summary of the emerging usage of liposomes in the food industry as delivery vehicles of nutrients, nutraceuticals, food additives, and food antimicrobials is provided.

  17. 热力学及动力学因素对L-S相转化法制备非对称膜结构与性能的影响%Effect of thermodynamic and kinetic factors on structure and performance of asymmetric membrane formed via L-S phase inversion

    Institute of Scientific and Technical Information of China (English)



    采用L-S相转化法制备非对称型分离膜的结构与性能取决于其制膜过程的热力学及动力学因素,讨论了聚合物分子量及浓度、溶剂及溶剂化作用、添加剂、铸膜液温度等热力学因素对铸膜液结构的影响,以及溶荆蒸发速度、凝胶速度等动力学因素对于脱溶剂速度的影响,综述了相关的热力学及动力学影响因素的表征方法.%This article defined and provided an overview of the essential affecting factors for the structure and performances of polymeric membranes with asymmectric structure prepared by L-S phase inversion process. The effect of vital thermodynamic factors, including the molecular weight and concentration of polymer, the solvent and its solvation, the additive selection, and the temperature of casting solution on the structure of casting solution; as well as the impact of critical kinetic factors, such as the solvent evaporation rate and gelation rate on the desolvation rate of the nascent membrane, were systemetically discussed. The methods to charicterize the relavent thermodynamic and kinetic affecting factors were also reviewed.

  18. "Smart" liposomal nanocontainers in biology and medicine. (United States)

    Tarahovsky, Y S


    The perspectives of using liposomes for delivery of drugs to desired parts of the human body have been intensively investigated for more than 30 years. During this time many inventions have been suggested and different kinds of liposomal devices developed, and a number of them have reached the stages of preclinical or clinical trials. The latest techniques can be used to develop biocompatible nano-sized liposomal containers having some abilities of artificial intellect, such as the presence of sensory and responsive units. However, only a few have been clinically approved. Further improvements in this area depend on our knowledge of the interactions of drugs with the lipid bilayer of liposomes. Further studies on liposomal transport through the human body, their targeting of cells requiring therapeutic treatment, and finally, the development of techniques for controlled drug delivery to desired acceptors on cell surfaces or in cytoplasm are still required.

  19. In vivo applications of PEG liposomes: unexpected observations.

    NARCIS (Netherlands)

    Laverman, P.; Boerman, O.C.; Storm, G.


    Recent studies with PEG liposomes in patients have consistently shown that liposomes can induce side effects (flushing, tightness of the chest). Furthermore, the blood clearance of PEG liposomes was shown to be dose-dependent: at lipid doses lower than 1 micromol/kg, PEG liposomes do not show the

  20. Pharmacokinetics of temoporfin-loaded liposome formulations: correlation of liposome and temoporfin blood concentration. (United States)

    Decker, Christiane; Schubert, Harald; May, Sylvio; Fahr, Alfred


    Liposomal formulations of the highly hydrophobic photosensitizer temoporfin were developed in order to overcome solubility-related problems associated with the current therapy scheme. We have incorporated temoporfin into liposomes of varying membrane composition, cholesterol content, and vesicle size. Specifically, two phosphatidyl oligoglycerols were compared to PEG2000-DSPE with respect to the ability to prolong circulation half life of the liposomal carrier. We measured the resulting pharmacokinetic profile of the liposomal carrier and the incorporated temoporfin in a rat model employing a radioactive lipid label and (14)C-temoporfin. The data for the removal of liposomes and temoporfin were analyzed in terms of classical pharmacokinetic theory assuming a two-compartment model. This model, however, does not allow in a straightforward manner to distinguish between temoporfin eliminated together with the liposomal carrier and temoporfin that is first transferred to other blood components (e. g. plasma proteins) before being eliminated from the blood. We therefore additionally analyzed the data based on two separate one-compartment models for the liposomes and temoporfin. The model yields the ratio of the rate constant of temoporfin elimination together with the liposomal carrier and the rate constant of temoporfin elimination following the transfer to e. g. plasma proteins. Our analysis using this model demonstrates that a fraction of temoporfin is released from the liposomes prior to being eliminated from the blood. In case of unmodified liposomes this temoporfin release was observed to increase with decreasing bilayer fluidity, indicating an accelerated temoporfin transfer from gel-phase liposomes to e. g. plasma proteins. Interestingly, liposomes carrying either one of the three investigated surface-modifying agents did not adhere to the tendencies observed for unmodified liposomes. Although surface-modified liposomes exhibited improved pharmacokinetic

  1. Application of Various Types of Liposomes in Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Mehran Alavi


    Full Text Available Liposomes, due to their various forms, require further exploration. These structures can deliver both hydrophilic and hydrophobic drugs for cancer, antibacterial, antifungal, immunomodulation, diagnostics, ophtalmica, vaccines, enzymes and genetic elements. Preparation of liposomes results in different properties for these systems. In addition, based on preparation methods, liposomes types can be unilamellar, multilamellar and giant unilamellar; however, there are many factors and difficulties that affect the development of liposome drug delivery structure. In the present review, we discuss some problems that impact drug delivery by liposomes. In addition, we discuss a new generation of liposomes, which is utilized for decreasing the limitation of the conventional liposomes.

  2. Application of Various Types of Liposomes in Drug Delivery Systems. (United States)

    Alavi, Mehran; Karimi, Naser; Safaei, Mohsen


    Liposomes, due to their various forms, require further exploration. These structures can deliver both hydrophilic and hydrophobic drugs for cancer, antibacterial, antifungal, immunomodulation, diagnostics, ophtalmica, vaccines, enzymes and genetic elements. Preparation of liposomes results in different properties for these systems. In addition, based on preparation methods, liposomes types can be unilamellar, multilamellar and giant unilamellar; however, there are many factors and difficulties that affect the development of liposome drug delivery structure. In the present review, we discuss some problems that impact drug delivery by liposomes. In addition, we discuss a new generation of liposomes, which is utilized for decreasing the limitation of the conventional liposomes.

  3. L.S. Vygotsky in the 21st century

    Directory of Open Access Journals (Sweden)

    Ardila A.


    Full Text Available Although Lev Vygotsky’s interpretation of human cognition was proposed almost one century ago, new scientific and technological advances have significantly supported many of his ideas and hypotheses. His cultural-historical theory of psychological processes, and his contributions to educational psychology, have continued growing without interruption. In this paper, three of Vygotsky’s hypotheses are examined in light of 21st century scientific developments: The influence of cultural factors on human cognition. A diversity of research studies in different countries has corroborated the crucial impact of culture on cognitive test performance; The role of language in higher psychological processes. According to Vygotsky’s cultural-historical approach, cognitive processes (“complex psychological processes” are social in origin, but complex and hierarchical in their structure. Intrinsic to the systemic organization of higher cognitive processes is the engagement of external artifacts (objects, symbols, signs, which have an independent history of development within a culture; and The hypothesis that thought and general complex cognition is associated with certain “inner speech.” Some contemporary neuroimaging studies (particularly PET and fMRI analyzing “inner speech” have been carried out. These studies have attempted to find the areas of the brain involved in “inner speech.” These scientific advances significantly support Vygotsky’s interpretation of human cognition. It has been found that inner speech depends on activity in Broca’s area and related brain network activity in the left hemisphere. Hence, inner speech is closely related to grammar, language production, and executive functions. Vygotsky’s important contribution to the understanding of psychological processes has stimulated, and continues to stimulate, a substantial amount of research in this area.

  4. L.S. Vygotsky in the 21st century

    National Research Council Canada - National Science Library

    Ardila Alfredo


      Although Lev Vygotsky's interpretation of human cognition was proposed almost one century ago, new scientific and technological advances have significantly supported many of his ideas and hypotheses...

  5. Liposome imaging agents in personalized medicine

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Hansen, Anders Elias; Gabizon, Alberto;


    that selectively localize in tumor tissue can transport both drugs and imaging agents, which allows for a theranostic approach with great potential in personalized medicine. Radiolabeling of liposomes have for many years been used in preclinical studies for evaluating liposome in vivo performance and has been...... start to consider how to use imaging for patient selection and treatment monitoring in connection to nanocarrier based medicines. Nanocarrier imaging agents could furthermore have interesting properties for disease diagnostics and staging. Here, we review the major advances in the development...... of radiolabeled liposomes for imaging as a tool in personalized medicine....


    Directory of Open Access Journals (Sweden)

    Dash Tapaswi Rani


    Full Text Available Liposomes are microscopic phospholipid vescicles made of lipid bilayer which are the drug carrier for improving the delivery of therapeutic agents. Research on liposome technology has progressed from conventional vesicles (“first-generation liposomes” to “second-generation liposomes”, in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. A significant step in the development of long-circulating liposomes came with inclusion of the synthetic polymer poly-(ethylene glycol (PEG in liposome composition. Due to advancement in liposomal technology a number of liposomal formulations are available in market for clinical use, with gene delivery and cancer therapy and some formulations are under clinical trial. Reformulation of drugs in liposomes has provided an opportunity to enhance the therapeutic indices of various agents mainly through alteration in their biodistribution. This review discusses the basic principles of liposome structures and preparations, evaluation parameters of liposomal formulation, pharmacokinetics of liposomes and liposome-encapsulated drugs, the potential applications of liposomes in drug delivery with examples of formulations approved for clinical use, and the problems associated with further exploitation of this drug delivery system.

  7. Liposomes as delivery systems for antineoplastic drugs (United States)

    Medina, Luis Alberto


    Liposome drug formulations are defined as pharmaceutical products containing active drug substances encapsulated within the lipid bilayer or in the interior aqueous space of the liposomes. The main importance of this drug delivery system is based on its drastic reduction in systemic dose and concomitant systemic toxicity that in comparison with the free drug, results in an improvement of patient compliance and in a more effective treatment. There are several therapeutic drugs that are potential candidates to be encapsulated into liposomes; particular interest has been focused in therapeutic and antineoplastic drugs, which are characterized for its low therapeutic index and high systemic toxicity. The use of liposomes as drug carriers has been extensively justified and the importance of the development of different formulations or techniques to encapsulate therapeutic drugs has an enormous value in benefit of patients affected by neoplastic diseases.

  8. Liposomal anticancer therapy: pharmacokinetic and clinical aspects. (United States)

    Di Paolo, A


    Liposomes, which are vesicles composed of a phospholipid bilayer surrounding an aqueous milieu, represent a new strategy for anticancer drug delivery. Extravasation and accumulation of liposomal drugs within neoplastic tissues are possible because of the leaky vasculature and scarce lymphatic vessels of tumours (the enhanced permeability and retention effect). Furthermore, liposomal chemotherapeutic agents display distinctive pharmacokinetic characteristics, because they possess longer elimination half-lives, reduced clearance and smaller volume of distribution with respect to corresponding free drugs. Taken together, these features lead to highest levels of cytotoxic agents in tumours, as demonstrated in preclinical models and clinical trials, whereas healthy tissues are spared from toxicity. In fact, liposomal drugs (i.e., doxorubicin), alone or in combination with other cytotoxic agents, lead to improved clinical effectiveness and ameliorated toxicity profile with respect to corresponding free drugs when they are used for the treatment of metastatic breast and ovarian cancers, and Kaposi's sarcoma.

  9. Progress involving new techniques for liposome preparation

    Directory of Open Access Journals (Sweden)

    Zhenjun Huang


    Full Text Available The article presents a review of new techniques being used for the preparation of liposomes. A total of 28 publications were examined. In addition to the theories, characteristics and problems associated with traditional methods, the advantages and drawbacks of the latest techniques were reviewed. In the light of developments in many relevant areas, a variety of new techniques are being used for liposome preparation and each of these new technique has particular advantages over conventional preparation methods. However, there are still some problems associated with these new techniques that could hinder their applications and further improvements are needed. Generally speaking, due to the introduction of these latest techniques, liposome preparation is now an improved procedure. These applications promote not only advances in liposome research but also the methods for their production on an industrial scale.

  10. Heterogeneous PNA Liposomes for Gene Delivery (United States)

    Marques, Bruno; Morfesis, Ana; Yoon, Diana; Schneider, James


    To circumvent complications of DNA adsorption onto cationic liposomes (i.e. structural reorganization, cytotoxicity), we have developed a liposomal system that binds genetic material via hydrogen bonding interactions. These liposomes contain surfactants linked to peptide nucleic acid (PNA), a synthetic DNA mimic with unique DNA-binding properties. We target multiple short regions of the DNA strand, sequestering the DNA from nuclease in solution, to protect it from nuclease digestion. Here, we present zeta potential measurements quantifying the extent of PNA incorporation in the liposomes, as well as the extent of DNA binding and nuclease activity under various conditions for mixtures of di- and trinucleotide PNA. We also discuss our attempts to identify the minimal PNA oligomer length to achieve stable binding and sequence specificity.

  11. Scale-Up of Liposome Manufacturing


    Wiggenhorn, Michael


    The study provides a comprehensive overview on different stabilization techniques for liposomal formulations. The selection of the appropriate technology for a particular formulation can thereby be based on several considerations. If free flowable particulate bulk material is desired the spraying-technologies are preferred over lyophilization. Another advantage of spraying-based technologies is the possibility to combine the liposome formation step and the drying step within the same process....

  12. Active loading of gemcitabine into liposomes


    Møkleby, Tormund Aasjord


    Gemcitabine is a well established anticancer compound, and is in use today against several types of cancers. Gemcitabine has a short half life. Formulations of gemcitabine containing liposomes could extend it's half life, thereby maybe improving its effectiveness. Also, liposomes in the smaller size range have an advantage when it comes to treating cancer. They accumulate at the site of the tumor, and stay there for a longer time than it would have done in normal tissue(Massing and Fuxius 2...

  13. Studies on Pharmacokinetics of Porcine Somatotropin Liposomes

    Institute of Scientific and Technical Information of China (English)

    XU Chuan-lai; JI Cheng; HAO Kai; LI Xiang-qian; YAO Hui-yuan


    This paper focuses on the pharmacokinetics in fattening pigs as well as the change of serum resulting from the use of porcine somatotropin(PST) and its liposomes. A slow-release model was determined to be relevant to following an examination of all dynamic parameters. The results indicate that the slow-release effect of PST liposomes was significant, with an extended release time of over 7 d.

  14. Physico-chemical characterization of liposomes and drug substance-liposome interactions in pharmaceutics using capillary electrophoresis and electrokinetic chromatography

    DEFF Research Database (Denmark)

    Franzen, Ulrik; Østergaard, Jesper


    Liposomes are self-assembled phospholipid vesicles and have numerous research and therapeutic applications. In the pharmaceutical and biomedical sciences liposomes find use as models of biological membranes, partitioning medium and as drug carriers. The present review addresses the use of capillary...... electrophoresis and liposome electrokinetic chromatography for the characterization of liposomes in a pharmaceutical context. Capillary electrophoretic techniques have been used for the measurement of electrophoretic mobility, which provides information on liposome surface charge, size and membrane permeability...... of liposomes. The use of liposome electrokinetic chromatography and capillary electrophoresis for determination of liposome/water partitioning and characterization of drug-liposome interactions is reviewed. A number of studies indicate that capillary electrophoresis may have a role in the characterization...

  15. Poly(ethylene glycol) on the liposome surface: on the mechanism of polymer-coated liposome longevity. (United States)

    Torchilin, V P; Omelyanenko, V G; Papisov, M I; Bogdanov, A A; Trubetskoy, V S; Herron, J N; Gentry, C A


    The hypothetical model is built explaining the molecular mechanism of protective action of poly(ethylene glycol) on liposomes in vivo. The protective layer of the polymer on the liposome surface is considered as a statistical 'cloud' of polymer possible conformations in solution. Computer simulation was used to demonstrate that relatively a small number of liposome-grafted molecules of hydrophilic and flexible polymer can create a dense protective conformational cloud over the liposome surface preventing opsonizing protein molecules from contacting liposome. A more rigid polymer fails to form this dense protective cloud, even when hydrophilic. Computer simulation was also used to reveal possible heterogeneity of reactive sites on a polymer-coated liposome surface, and to estimate the optimal polymer-to-lipid ratio for efficient liposome protection. Experiments have been performed with the quenching of liposome-associated fluorescent label (nitrobenzoxadiazole or fluorescein) with protein (rhodamine-ovalbumin or anti-fluorescein antibody) from solution. It was shown that poly(ethylene glycol) grafting to liposomes hinders protein interaction with the liposome surface, whereas liposome-grafted dextran (more rigid polymer) in similar quantities does not affect protein-liposome interaction. Highly-reactive and low-reactive populations of chemically identical reactive sites have been found on polymer-coated liposomes. Experimental data satisfactory confirm the suggested mechanism for the longevity of polymer-modified liposome.

  16. Ehrlich tumor inhibition using doxorubicin containing liposomes. (United States)

    Elbialy, Nihal Saad; Mady, Mohsen Mahmoud


    Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with saline, DOX in solution or DOX encapsulated within liposomes prepared from DMPC/CHOL/DPPG/PEG-PE (100:100:60:4) in molar ratio. Cytotoxicity assay showed that the IC50 of liposomes containing DOX was greater than that DOX only. Tumor growth inhibition curves in terms of mean tumor size (cm(3)) were presented. All the DOX formulations were effective in preventing tumor growth compared to saline. Treatment with DOX loaded liposomes displayed a pronounced inhibition in tumor growth than treatment with DOX only. Histopathological examination of the entire tumor sections for the various groups revealed marked differences in cellular features accompanied by varying degrees in necrosis percentage ranging from 12% for saline treated mice to 70% for DOX loaded liposome treated mice. The proposed liposomal formulation can efficiently deliver the drug into the tumor cells by endocytosis (or passive diffusion) and lead to a high concentration of DOX in the tumor cells. The study showed that the formulation of liposomal doxorubicin improved the therapeutic index of DOX and had increased anti-tumor activity against Ehrlich tumor models.

  17. Pegylated liposomal doxorubicin in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Robert Strother


    Full Text Available Robert Strother1,2, Daniela Matei1–51Department of Medicine, 2Indiana University Melvin and Bren Simon Cancer Center, 3Department of Obstetrics and Gynecology, 4Department of Biochemistry and Molecular Biology, 5VA Roudebush Hospital Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN, 46202Abstract: The encapsulation of doxorubicin in a pegylated liposomal matrix led to a reformulated agent with a different toxicity profile and improved clinical utility. Liposomal doxorubicin is devoid of the cardiac toxicity associated with doxorubicin, but is associated with predictable muco-cutaneous toxicity. The liposomal formulation leads to improved delivery to the target tumor tissue, allowing enhanced uptake by cancer cells. These properties translate into clinical utility in recurrent ovarian cancer as demonstrated by phase II and III trials, this proven clinical efficacy leading to FDA approval in second-line therapy for ovarian cancer. New combinations with cytotoxics, in particular with carboplatin, have demonstrated an acceptable toxicity profile and clinical utility in platinum-sensitive ovarian cancer. A favorable toxicity profile renders liposomal doxorubicin an ideal partner for combination regimens with other cytotoxics, and more recently with biological agents. Such combinations are the subject of ongoing clinical trials.Keywords: ovarian cancer, doxorubicin, liposomes, pegylated liposomal doxorubicin

  18. Liposomal amphotericin B: clinical experience and perspectives. (United States)

    Gibbs, Winter J; Drew, Richard H; Perfect, John R


    While amphotericin B deoxycholate (Fungizone, Apothecon Pharmaceuticals) has been considered by many to be the gold standard for the treatment for numerous invasive fungal infections for over 45 years, toxicities associated with its use often necessitate treatment modification or discontinuation. Lipid-based formulations, including liposomal amphotericin B (AmBisome, Fujisawa Healthcare, Inc.), were developed to decrease many of these toxicities while retaining broad antifungal spectrum and potency of amphotericin B. In clinical trials, liposomal amphotericin B has demonstrated efficacy comparable to that of amphotericin B deoxycholate while reducing the incidence of treatment-related nephrotoxicity, electrolyte-wasting, and infusion-related reactions. In addition, recent clinical trials have also compared liposomal amphotericin B with other antifungal classes. Acquisition costs of liposomal amphotericin B are substantially higher than those of amphotericin B deoxycholate and other antifungals. While pharmacoeconomic analyses consider outcomes and other treatment-related costs, they have yet to clearly demonstrate the cost-effectiveness of liposomal amphotericin B when compared with amphotericin B deoxycholate or other antifungal agents. This review will focus primarily on recent liposomal amphotericin B experience and attempt to put its use into perspective considering other available antifungal agents.

  19. Plasmon resonant liposomes for controlled drug delivery (United States)

    Knights-Mitchell, Shellie S.; Romanowski, Marek


    Nanotechnology use in drug delivery promotes a reduction in systemic toxicity, improved pharmacokinetics, and better drug bioavailability. Liposomes continue to be extensively researched as drug delivery systems (DDS) with formulations such as Doxil® and Ambisome® approved by FDA and successfully marketed in the United States. However, the limited ability to precisely control release of active ingredients from these vesicles continues to challenge the broad implementation of this technology. Moreover, the full potential of the carrier to sequester drugs until it can reach its intended target has yet to be realized. Here, we describe a liposomal DDS that releases therapeutic doses of an anticancer drug in response to external stimulus. Earlier, we introduced degradable plasmon resonant liposomes. These constructs, obtained by reducing gold on the liposome surface, facilitate spatial and temporal release of drugs upon laser light illumination that ultimately induces an increase in temperature. In this work, plasmon resonant liposomes have been developed to stably encapsulate and retain doxorubicin at physiological conditions represented by isotonic saline at 37o C and pH 7.4. Subsequently, they are stimulated to release contents either by a 5o C increase in temperature or by laser illumination (760 nm and 88 mW/cm2 power density). Successful development of degradable plasmon resonant liposomes responsive to near-infrared light or moderate hyperthermia can provide a new delivery method for multiple lipophilic and hydrophilic drugs with pharmacokinetic profiles that limit clinical utility.

  20. New drug candidates for liposomal delivery identified by computer modeling of liposomes' remote loading and leakage. (United States)

    Cern, Ahuva; Marcus, David; Tropsha, Alexander; Barenholz, Yechezkel; Goldblum, Amiram


    Remote drug loading into nano-liposomes is in most cases the best method for achieving high concentrations of active pharmaceutical ingredients (API) per nano-liposome that enable therapeutically viable API-loaded nano-liposomes, referred to as nano-drugs. This approach also enables controlled drug release. Recently, we constructed computational models to identify APIs that can achieve the desired high concentrations in nano-liposomes by remote loading. While those previous models included a broad spectrum of experimental conditions and dealt only with loading, here we reduced the scope to the molecular characteristics alone. We model and predict API suitability for nano-liposomal delivery by fixing the main experimental conditions: liposome lipid composition and size to be similar to those of Doxil® liposomes. On that basis, we add a prediction of drug leakage from the nano-liposomes during storage. The latter is critical for having pharmaceutically viable nano-drugs. The "load and leak" models were used to screen two large molecular databases in search of candidate APIs for delivery by nano-liposomes. The distribution of positive instances in both loading and leakage models was similar in the two databases screened. The screening process identified 667 molecules that were positives by both loading and leakage models (i.e., both high-loading and stable). Among them, 318 molecules received a high score in both properties and of these, 67 are FDA-approved drugs. This group of molecules, having diverse pharmacological activities, may be the basis for future liposomal drug development.

  1. Dendritic Cells Stimulated by Cationic Liposomes. (United States)

    Vitor, Micaela Tamara; Bergami-Santos, Patrícia Cruz; Cruz, Karen Steponavicius Piedade; Pinho, Mariana Pereira; Barbuto, José Alexandre Marzagão; De La Torre, Lucimara Gaziola


    Immunotherapy of cancer aims to harness the immune system to detect and destroy cancer cells. To induce an immune response against cancer, activated dendritic cells (DCs) must present tumor antigens to T lymphocytes of patients. However, cancer patients' DCs are frequently defective, therefore, they are prone to induce rather tolerance than immune responses. In this context, loading tumor antigens into DCs and, at the same time, activating these cells, is a tempting goal within the field. Thus, we investigated the effects of cationic liposomes on the DCs differentiation/maturation, evaluating their surface phenotype and ability to stimulate T lymphocytes proliferation in vitro. The cationic liposomes composed by egg phosphatidylcholine, 1,2-dioleoyl-3-trimethylammonium propane and 1,2-dioleoylphosphatidylethanolamine (50/25/25% molar) were prepared by the thin film method followed by extrusion (65 nm, polydispersity of 0.13) and by the dehydration-rehydration method (95% of the population 107 nm, polydispersity of 0.52). The phenotypic analysis of dendritic cells and the analysis of T lymphocyte proliferation were performed by flow cytometry and showed that both cationic liposomes were incorporated and activated dendritic cells. Extruded liposomes were better incorporated and induced higher CD86 expression for dendritic cells than dehydrated-rehydrated vesicles. Furthermore, dendritic cells which internalized extruded liposomes also provided stronger T lymphocyte stimulation. Thus, cationic liposomes with a smaller size and polydispersity seem to be better incorporated by dendritic cells. Hence, these cationic liposomes could be used as a potential tool in further cancer immunotherapy strategies and contribute to new strategies in immunotherapy.


    Directory of Open Access Journals (Sweden)

    Derkach SA


    Full Text Available Nowadays the vital problem of modern medicine is a tendency to emerging of both nosocomial and community-acquired strains before antibiotic resistance forming. The complexity of antibiotic therapy of diseases caused by methicillin resistant staphylococci having high poly resistance almost to every classes of antibacterial agents is of prime importance. One of the ways to improve antibacterial preparations still remains the development of their liposomal forms. This work studies antistaphylococcal activity (according to MIC of the liposomal form of lincomycin developed in the Institute of Dermatology and Venereology of Ukraine by Ivanova N. N., the Candidate of Сhemical Sciences.The purpose of this research work was to study liposomal inhibiting concentration of the liposomalny form of lincomycin and a commercial preparation lincomycin (produced by CJSC “Pharmaceutical firm "Darnitsa". Determination of the minimum inhibiting concentration was carried out by a tablet micromethod by consecutive cultivations of the samples under study.It is shown that MIC of liposomal lincomycin is eight times as low as usual lincomycin (0,23mkg/ml to 1,87 mkg/ml. Antibacterial activity of the liposomal form of lincomycin is studied concerning the patients selected from the different biotopes with pyo inflammatory diseases of staphylococcus strains (15 strains – methicillin sensitive, 12 strains - methicillin resistant.It is shown authentically the higher sensitivity of S. aureus strains to the liposomal form of lincomycin in comparison with usual lincomycin . Also 50.0% of MRSA strains were sensitive to the liposomalny form of lincomycin that shows the perspective for the development of the liposomal forms of antibiotics to cure staphylococcal infections.

  3. A Review on Composite Liposomal Technologies for Specialized Drug Delivery

    Directory of Open Access Journals (Sweden)

    Maluta S. Mufamadi


    Full Text Available The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. Two approaches for overcoming the factors related to the suboptimal efficacy of liposomes in drug delivery have been suggested. The first entails modifying the liposome surface with functional moieties, while the second involves integration of pre-encapsulated drug-loaded liposomes within depot polymeric scaffolds. This attempts to provide ingenious solutions to the limitations of conventional liposomes such as short plasma half-lives, toxicity, stability, and poor control of drug release over prolonged periods. This review delineates the key advances in composite technologies that merge the concepts of depot polymeric scaffolds with liposome technology to overcome the limitations of conventional liposomes for pharmaceutical applications.

  4. Liposomal dry powders as aerosols for pulmonary delivery of proteins


    Lu, Dongmei; Hickey, Anthony J.


    The purpose of this research was to develop liposomal dry powder aerosols for protein delivery. The delivery of stable protein formulations is essential for protein subunit vaccine delivery, which requires local delivery to macrophages in the lungs. β-Glucuronidase (GUS) was used as a model protein to evaluate dry powder liposomes as inhaled delivery vehicles. Dimyristoyl phosphatylcholine:cholesterol (7∶3) was selected as the liposome composition. The lyophilization of liposomes, micronizati...

  5. Liposomal amphotericin B for the treatment of visceral leishmaniasis


    Bern, C.; Adler-Moore, J.; Berenguer, J.; Boelaert, M; van den Boer, M.; Davidson, R N; Figueras, C; Gradoni, L.; Kafetzis, D. A.; Ritmeijer, E.; Rosenthal, E.; Royce, C; Russo, R; Sundar, S; Alvar, J.


    During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). The World Health Organization convened a workshop to review current knowledge and to develop guidelines for liposomal amphotericin B use for VL. In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia, the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferential pricing for nonprofit ...

  6. Use of liposomes as injectable-drug delivery systems. (United States)

    Ostro, M J; Cullis, P R


    The formation of liposomes and their application as delivery systems for injectable drugs are described. Liposomes are microscopic vesicles composed of one or more lipid membranes surrounding discrete aqueous compartments. These vesicles can encapsulate water-soluble drugs in their aqueous spaces and lipid-soluble drugs within the membrane itself. Liposomes release their contents by interacting with cells in one of four ways: adsorption, endocytosis, lipid exchange, or fusion. Liposome-entrapped drugs are distributed within the body much differently than free drugs; when administered intravenously to healthy animals and humans, most of the injected vesicles accumulate in the liver, spleen, lungs, bone marrow, and lymph nodes. Liposomes also accumulate preferentially at the sites of inflammation and infection and in some solid tumors; however, the reason for this accumulation is not clear. Four major factors influence liposomes' in vivo behavior and biodistribution: (1) liposomes tend to leak if cholesterol is not included in the vesicle membrane, (2) small liposomes are cleared more slowly than large liposomes, (3) the half-life of a liposome increases as the lipid dose increases, and (4) charged liposomal systems are cleared more rapidly than uncharged systems. The most advanced application of liposome-based therapy is in the treatment of systemic fungal infections, especially with amphotericin B. Liposomes are also under investigation for treatment of neoplastic disorders. Liposomes' uses in cancer therapy include encapsulation of known antineoplastic agents such as doxorubicin and methotrexate, delivery of immune modulators such as N-acetylmuramyl-L-alanine-D-isoglutamine, and encapsulation of new chemical entities that are synthesized with lipophilic segments tailored for insertion into lipid bilayers. Liposomal formulations of injectable antimicrobial agents and antineoplastic agents already are undergoing clinical testing, and most probably will receive

  7. Amphiphilic vinyl polymers effectively prolong liposome circulation time in vivo. (United States)

    Torchilin, V P; Shtilman, M I; Trubetskoy, V S; Whiteman, K; Milstein, A M


    Newly synthesized amphiphilic polyacrylamide and poly(vinyl pyrrolidone), single terminus-modified with long-chain fatty acyl groups, are able to incorporate into the liposomal membrane, and similar to poly(ethylene glycol) prolong liposome circulation in vivo and decrease liposome accumulation in the liver. Protective efficacy of modified polymers increases with the increase in the length of acyl moiety and decreases for higher molecular weight polymers. The data on amphiphilic polymer-modified liposome biodistribution are presented.

  8. MRI shows clodronate-liposomes attenuating liverinjuryinratswithsevereacutepancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jian-Xin Zhang; Sheng-Chun Dang; Yong Zhang; Xin Sha; Li-Rong Zhang; Chuan-She Wei; Min Chen; De-Li Jiang


    BACKGROUND: Studies have revealed that macrophages play an important role in the development of severe acute pancreatitis (SAP). Activated macrophages can lead to a systemic inlfammatory response, induce lipid peroxidation, impair membrane structure, result in injury to the liver and the other extrahepatic organs, and eventually result in multiple organ dysfunction syndrome by promoting excessive secretion of cytokines. Liver injury can further aggravate the systemic inlfammatory response and increase mortality by affecting the metabolism of toxins and the release of excessive inlfammatory mediators. Clodronate is a synthetic bisphosphonate, which is often used for treating bone changes caused by osteoporosis and other factors. In the current study, we created liposomes containing superparamagnetic iron oxide particles (SPIOs) for macrophage labeling and magnetic resonance imaging, using a novel method that can bind the clodronate to induce apoptosis and deplete macrophages. METHODS: Superparamagnetic Fe3O4 nanoparticles were prepared by chemical coprecipitation. SPIO-containing liposomes and SPIO-clodronate-containing liposomes were prepared by the thin iflm method. SAP models were prepared by injection of sodium taurocholate (2 ml/kg body weight) into the subcapsular space of the pancreas. Sprague-Dawley rats were randomly divided into a control group, a SAP plus SPIO-liposome group, and a SAP plus SPIO-clodronate-containing group. Two and six hours after SAP models were available, T2-weighted MRI scans (in the same plane) of the livers of rats in each group were performed. At the end of the scans, 2 ml of blood was taken from the superior mesenteric vein to measure the levels of serum amylase, ALT, AST, TNF-α, and IL-6. Pathological changes in the liver and pancreas were assessed. RESULTS: Transmission electron microscopy showed that the liposomes had a uniform size. No pathological changes in the pancreata of rats in the control group were noted. The

  9. Acoustical Properties of Individual Liposome-Loaded Microbubbles

    NARCIS (Netherlands)

    Luan, Y.; Faez, T.; Gelderblom, E.C.; Skachkov, I.; Geers, B.; Lentacker, I.; Steen, van der T.; Versluis, M.; Jong, de N.


    A comparison between phospholipid-coated microbubbles with and without liposomes attached to the microbubble surface was performed using the ultra-high-speed imaging camera (Brandaris 128). We investigated 73 liposome-loaded microbubbles (loaded microbubbles) and 41 microbubbles without liposome loa

  10. Liposome-hepatocyte interactions : The role of plasma proteins

    NARCIS (Netherlands)

    Yan, Xuedong


    Liposomes have proved to be a useful drug delivery system as evidenced by several liposomal products that have reached the market in recent years [1]. However, many obstacles, such as low efficiency and specificity in delivering macromolecules to target sites, need to be overcome before liposomal dr

  11. Treatment of Digital Ischemia with Liposomal Bupivacaine

    Directory of Open Access Journals (Sweden)

    José Raul Soberón


    Full Text Available Objective. This report describes a case in which the off-label use of liposomal bupivacaine (Exparel in a peripheral nerve block resulted in marked improvement of a patient’s vasoocclusive symptoms. The vasodilating and analgesic properties of liposomal bupivacaine in patients with ischemic symptoms are unknown, but our clinical experience suggests a role in the management of patients suffering from vasoocclusive disease. Case Report. A 45-year-old African American female was admitted to the hospital with severe digital ischemic pain. She was not a candidate for any vascular surgical or procedural interventions. Two continuous supraclavicular nerve blocks were placed with modest clinical improvement. These effects were also short-lived, with the benefits resolving after the discontinuation of the peripheral nerve blocks. She continued to report severe pain and was on multiple anticoagulant medications, so a decision was made to perform an axillary nerve block using liposomal bupivacaine (Exparel given the compressibility of the site as well as the superficial nature of the target structures. Conclusions. This case report describes the successful off-label usage of liposomal bupivacaine (Exparel in a patient with digital ischemia. Liposomal bupivacaine (Exparel is currently FDA approved only for wound infiltration use at this time.

  12. A novel liposomal formulation of flavopiridol. (United States)

    Yang, Xiaojuan; Zhao, Xiaobin; Phelps, Mitch A; Piao, Longzhu; Rozewski, Darlene M; Liu, Qing; Lee, L James; Marcucci, Guido; Grever, Michael R; Byrd, John C; Dalton, James T; Lee, Robert J


    Flavopiridol has shown promising activities in hematologic and solid tumor models, as well as in clinical trials in chronic lymphocytic leukemia patients. Flavopiridol has relatively low solubility and high plasma protein-binding. To address these issues and to provide an alternative strategy to achieve clinical efficacy, we encapsulated flavopiridol into a liposomal carrier and characterized its physicochemical and pharmacokinetic properties. The liposomes, comprising hydrogenated soy phosphatidylcholine (HSPC), cholesterol and poly (ethylene glycol) 2000-distearoyl phosphatidylethanolamine (PEG-DSPE), were prepared by polycarbonate membrane extrusion and then loaded with flavopiridol by a pH-gradient driven remote loading procedure. The liposomes had a mean diameter of 120.7 nm and a flavopiridol entrapment efficiency of 70.4%. Pharmacokinetic study in mice after i.v. bolus injection showed that the liposomal flavopiridol had an increased elimination phase half-life (T((1/2)beta), 339.7 min vs. 57.0 min), decreased clearance (CL, 0.012 L/min vs. 0.036 L/min), and increased area under the plasma concentration-time curve (AUC, 10.8 min micromol/L vs. 3.4 min micromol/L) compared to the free drug. This indicates a significant and potentially beneficial change in flavopiridol pharmacokinetics for the liposomal formulation. Further preclinical studies are warranted to define the toxicity and therapeutic efficacy of this novel formulation.

  13. Lactosamination of liposomes and hepatotropic targeting research

    Institute of Scientific and Technical Information of China (English)

    Yong Peng Chen; Lian Zhang; Qiao Sheng Lu; Xiao Rong Feng; Kang Xian Luo


    Site-specific delivery of therapeutic drugs to their target cells is a major scientific challenge for the pharmaceutical sciences. It offers a number of advantages over conventional drug administration. With drug targeting, high local concentrations of the drug can be achieved, thus circumventing many unwanted side effects. Various carriers have been suggested for the delivery of drugs, including liposomes[1 - 5] and (neo ) glycoproteins[6-8]. The asialoglycoprotein receptor (ASGP-R) has frequently been utilized for targeting drugs to the parenchymal liver cell[6- 12]. Liposomes have several advantageous characteristics as drug carrier, and particularly, ligandtacked liposomes achieve a highly effective targeting[13]. Hara et al reported that asialofetuin (AF)-tacked liposomes distributed to rat hepatocytes selectively in vivo[14], and ASGP-R mediated the uptake of AF-liposomes encapsulating IFN-γ by isolated rat hepatocytes in vitro[15]. Lactosaminated human serum albumin (L-HSA) is a neoglycoprotein taking number of galactose residue as terminal sugar[6].

  14. Liposome-Loaded Cell Backpacks. (United States)

    Polak, Roberta; Lim, Rosanna M; Beppu, Marisa M; Pitombo, Ronaldo N M; Cohen, Robert E; Rubner, Michael F


    Cell backpacks, or micron-scale patches of a few hundred nanometers in thickness fabricated by layer-by-layer (LbL) assembly, are potentially useful vehicles for targeted drug delivery on the cellular level. In this work, echogenic liposomes (ELIPs) containing the anticancer drug doxorubicin (DOX) are embedded into backpacks through electrostatic interactions and LbL assembly. Poly(allylamine hydrochloride)/poly(acrylic acid) (PAH/PAA)n , and poly(diallyldimethylammonium chloride)/poly(styrene sulfonate) (PDAC/SPS)n film systems show the greatest ELIP incorporation of the films studied while maintaining the structural integrity of the vesicles. The use of ELIPs for drug encapsulation into backpacks facilitates up to three times greater DOX loading compared to backpacks without ELIPs. Cytotoxicity studies reveal that monocyte backpack conjugates remain viable even after 72 h, demonstrating promise as drug delivery vehicles. Because artificial vesicles can load many different types of drugs, ELIP containing backpacks offer a unique versatility for broadening the range of possible applications for cell backpacks.

  15. Magnetic nanoparticles for "smart liposomes". (United States)

    Nakayama, Yoshitaka; Mustapić, Mislav; Ebrahimian, Haleh; Wagner, Pawel; Kim, Jung Ho; Hossain, Md Shahriar Al; Horvat, Joseph; Martinac, Boris


    Liposomal drug delivery systems (LDDSs) are promising tools used for the treatment of diseases where highly toxic pharmacological agents are administered. Currently, destabilising LDDSs by a specific stimulus at a target site remains a major challenge. The bacterial mechanosensitive channel of large conductance (MscL) presents an excellent candidate biomolecule that could be employed as a remotely controlled pore-forming nanovalve for triggered drug release from LDDSs. In this study, we developed superparamagnetic nanoparticles for activation of the MscL nanovalves by magnetic field. Synthesised CoFe2O4 nanoparticles with the radius less than 10 nm were labelled by SH groups for attachment to MscL. Activation of MscL by magnetic field with the nanoparticles attached was examined by the patch clamp technique showing that the number of activated channels under ramp pressure increased upon application of the magnetic field. In addition, we have not observed any cytotoxicity of the nanoparticles in human cultured cells. Our study suggests the possibility of using magnetic nanoparticles as a specific trigger for activation of MscL nanovalves for drug release in LDDSs.

  16. Liposomal membrane disruption by means of miniaturized dielectric-barrier discharge in air: liposome characterization (United States)

    Svarnas, P.; Asimakoulas, L.; Katsafadou, M.; Pachis, K.; Kostazos, N.; Antimisiaris, S. G.


    The increasing interest of the plasma community in the application of atmospheric-pressure cold plasmas to bio-specimen treatment has led to the creation of the emerging field of plasma biomedicine. Accordingly, plasma setups based on dielectric-barrier discharges have already been widely tested for the inactivation of various cells. Most of these systems refer to the plasma jet concept where noble gases penetrate atmospheric air and are subjected to the influence of high electric fields, thus forming guided streamers. Following the original works of our group where liposomal membranes were proposed as models for studying the interaction between plasma jets and cells, we present herein a study on liposomal membrane disruption by means of miniaturized dielectric-barrier discharge running in atmospheric air. Liposomal membranes of various lipid compositions, lamellarities, and sizes are treated at different times. It is shown that the dielectric-barrier discharge of low mean power leads to efficient liposomal membrane disruption. The latter is achieved in a controllable manner and depends on liposome properties. Additionally, it is clearly demonstrated that liposomal membrane disruption takes place even after plasma extinction, i.e. during post-treatment, resembling thus an ‘apoptosis’ effect, which is well known today mainly for cell membranes. Thus, the adoption of the present concept would be beneficial for tailoring studies on plasma-treated cell-mimics. Finally, the liposome treatment is discussed with respect to possible physicochemical mechanisms and potential discharge modification due to the various compositions of the liquid electrode.

  17. In vitro characteristics of liposomes and double liposomes prepared using a novel glass beads method. (United States)

    Yamabe, Kenji; Kato, Yoshinori; Onishi, Hiraku; Machida, Yoshiharu


    A novel preparative method for liposomes and double liposomes (DL) using glass beads was superior to a glass-filter method developed previously. Lipid dissolved in chloroform was poured into a kjeldahl flask with glass beads (BZ-04, 0.350-0.500 mm phi; BZ-3, 2.794-3.962 mm phi; or BZ-6, 5.613-6.680 mm phi), and the organic solvent was evaporated. The lipid layer that formed on the glass beads was hydrated with 1.5 ml of the suspension of inner liposomes at a temperature above the phase transition temperature of the lipids employed, and was agitated vigorously. Erythrosine (ER) was used as a model drug. The size of liposomes prepared by the glass beads method depended on the size of the glass beads. The size of the liposomes became smaller as glass beads with a smaller size were used. A high encapsulation efficiency was observed when glass bead blends consisting of two different sizes were used. Large sizes (BZ-3/BZ-6) had a tendency to show high encapsulation efficiency and size also played an important role in the formation of liposomes. DL formation inhibited the release of ER and DL formative efficiency was markedly improved by means of the glass beads method. These findings suggested that the glass beads method developed in this study conferred a high drug loading and a high DL formation on liposomes compared with ordinary methods.

  18. Imaging-based analysis of liposome internalization to macrophage cells: Effects of liposome size and surface modification with PEG moiety. (United States)

    Lee, Jae Sun; Hwang, Sang Youn; Lee, E K


    Liposome is one of the frequently used carriers for active targeting systems in vivo. Such parameters as its size, surface charge, and surface modifiers are known to influence the liposome uptake by macrophage cells. In this study, we investigated the effects of liposome size and polyethylene glycol (PEG) surface modifier on the liposomal internalization to murine macrophage (RAW-264.7), by using an imaging analysis technique. Three different sized liposomes (100, 200, and 400 nm in nominal diameter) labeled with rhodamine fluorescence were used. Liposome internalization appeared to reach a pseudo-steady plateau in about 5h incubation, and most of the internalized liposomes were seen to accumulate in the cytosol including cellular extensions. The maximum fluorescent density from the internalized liposomes was similar between 100 nm and 200 nm liposomes. However, that of the larger 400 nm liposome was approximately 1.7 times higher than the others, confirming the previous report that the larger the liposomes are the higher the degree of internalization is. When the outside of the 200 nm liposomes was modified with biocompatible anchor molecule (BAM) consisting of PEG (ca. 2kD molecular weight) moiety, the endocytosis was indeed reduced by about 2.1-fold, despite the increase of the hydrodynamic size due to BAM conjugation. This fluorescence-based cellular imaging analysis can be used to quantitatively monitor and optimize cellular internalization systems.

  19. Lymphatic uptake and biodistribution of liposomes after subcutaneous injection - IV. Fate of liposomes in regional lymph nodes

    NARCIS (Netherlands)

    Oussoren, C; Scherphof, G; van der Want, JJ; van Rooijen, N; Storm, G


    The ability of clodronate-containing liposomes to deplete lymph nodes of macrophages was used as a tool to investigate the fate of liposomes in regional lymph nodes after subcutaneous (s.c.) administration. Reduced lymph node localization of liposomes in macrophage-depleted lymph nodes confirmed

  20. Scintigraphic visualization of intrathecal liposome biodistribution. (United States)

    Umbrain, V; D'Haese, J; Alafandy, M; De Roover, E; Schoutens, A; Van Gansbeke, B; Albert, A; Goffinet, G; Camu, F; Legros, F J


    Liposomes containing local anaesthetics have been administered intrathecally and in the epidural space. Poor attention has been given to the pharmacokinetics of liposomes as drug carriers. Therefore, we observed the biodistribution of liposomes after intrathecal injection in rats by scintigraphic imaging during 24 h. We administered 99mTc-labeled multilamellar (MLV) and small unilamellar vesicles (SUV) of defined size and volume dispersities into the cerebrospinal fluid at the lumbar level. Those vesicles were free of contamination by radiolabeled colloids as visualized by light and electron microscopy and of neurotoxic products from phosphatidylcholine hydrolysis and peroxidation, both during the preparation process and after 24 h incubation in cerebrospinal fluid at 37 degrees C in vitro. SUV immediately diffused from the lumbar site of injection to the head and were cleared between 1 and 24 h after injection. MLV were cleared more slowly from the spinal space and appeared in the head region 1 h after injection where they accumulated up to 24 h. These differences were explained in terms of vesicle sizes and volumes. SUV with 0.05 micron diameters were rapidly absorbed into the blood through the arachnoid granulations. In contrast, particles larger than the upper size limit of the arachnoid granulations permeability (+/- 8 microns) could accumulate in the head with a slow elimination rate. This difference in clearance from the intrathecal space outlines the importance of defining the size of the liposomes, the distribution of a tracer or a drug inside the liposomal preparation, the chemical stability and the absence of toxic degradation products of liposome formulations before clinical use.

  1. Microfluidic-enabled liposomes elucidate size-dependent transdermal transport.

    Directory of Open Access Journals (Sweden)

    Renee R Hood

    Full Text Available Microfluidic synthesis of small and nearly-monodisperse liposomes is used to investigate the size-dependent passive transdermal transport of nanoscale lipid vesicles. While large liposomes with diameters above 105 nm are found to be excluded from deeper skin layers past the stratum corneum, the primary barrier to nanoparticle transport, liposomes with mean diameters between 31-41 nm exhibit significantly enhanced penetration. Furthermore, multicolor fluorescence imaging reveals that the smaller liposomes pass rapidly through the stratum corneum without vesicle rupture. These findings reveal that nanoscale liposomes with well-controlled size and minimal size variance are excellent vehicles for transdermal delivery of functional nanoparticle drugs.

  2. Recent Trends of Polymer Mediated Liposomal Gene Delivery System

    Directory of Open Access Journals (Sweden)

    Shyamal Kumar Kundu


    Full Text Available Advancement in the gene delivery system have resulted in clinical successes in gene therapy for patients with several genetic diseases, such as immunodeficiency diseases, X-linked adrenoleukodystrophy (X-ALD blindness, thalassemia, and many more. Among various delivery systems, liposomal mediated gene delivery route is offering great promises for gene therapy. This review is an attempt to depict a portrait about the polymer based liposomal gene delivery systems and their future applications. Herein, we have discussed in detail the characteristics of liposome, importance of polymer for liposome formulation, gene delivery, and future direction of liposome based gene delivery as a whole.

  3. Liposomes as a gene delivery system

    Directory of Open Access Journals (Sweden)

    C. Ropert


    Full Text Available Gene therapy is an active field that has progressed rapidly into clinical trials in a relatively short time. The key to success for any gene therapy strategy is to design a vector able to serve as a safe and efficient gene delivery vehicle. This has encouraged the development of nonviral DNA-mediated gene transfer techniques such as liposomes. Many liposome-based DNA delivery systems have been described, including molecular components for targeting given cell surface receptors or for escaping from the lysosomal compartment. Another recent technology using cationic lipids has been evaluated and has generated substantial interest in this approach to gene transfer.

  4. Liposomes for Use in Gene Delivery

    Directory of Open Access Journals (Sweden)

    Daniel A. Balazs


    Full Text Available Liposomes have a wide array of uses that have been continuously expanded and improved upon since first being observed to self-assemble into vesicular structures. These arrangements can be found in many shapes and sizes depending on lipid composition. Liposomes are often used to deliver a molecular cargo such as DNA for therapeutic benefit. The lipids used to form such lipoplexes can be cationic, anionic, neutral, or a mixture thereof. Herein physical packing parameters and specific lipids used for gene delivery will be discussed, with lipids classified according to overall charge.

  5. Therapeutic gas delivery via microbubbles and liposomes. (United States)

    Fix, Samantha M; Borden, Mark A; Dayton, Paul A


    Gaseous molecules including nitric oxide, hydrogen sulfide, carbon monoxide and oxygen mediate numerous cell signaling pathways and have important physiological roles. Several noble gasses have been shown to elicit biological responses. These bioactive gasses hold great therapeutic potential, however, their controlled delivery remains a significant challenge. Recently, researchers have begun using microbubbles and liposomes to encapsulate such gasses for parenteral delivery. The resultant particles are acoustically active, and ultrasound can be used to stimulate and/or image gas release in a targeted region. This review provides a summary of recent advances in therapeutic gas delivery using microbubbles and liposomes.

  6. Liposomes as signal amplification reagents for bioassays in microfluidic channels. (United States)

    Locascio, Laurie E; Hong, Jennifer S; Gaitan, Michael


    Liposomes with encapsulated carboxyfluorescein were used in an affinity-based assay to provide signal amplification for small-volume fluorescence measurements. Microfluidic channels were fabricated by imprinting in a plastic substrate material, poly(ethylene terephthalate glycol) (PETG), using a silicon template imprinting tool. Streptavidin was linked to the surface through biotinylated-protein for effective immobilization with minimal nonspecific adsorption of the liposome reagent. Lipids derivatized with biotin were incorporated into the liposome membrane to make the liposomes reactive for affinity assays. Specific binding of the liposomes to microchannel walls, dependence of binding on incubation time, and nonspecific adsorption of the liposome reagent were evaluated. The results of a competitive assay employing liposomes in the microchannels are presented.

  7. Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary insulin delivery. (United States)

    Chono, Sumio; Fukuchi, Rie; Seki, Toshinobu; Morimoto, Kazuhiro


    The pulmonary insulin delivery characteristics of liposomes were examined. Aerosolized liposomes containing insulin were administered into rat lungs and the enhancing effect on insulin delivery was evaluated by changes of plasma glucose levels. Liposomes with dipalmitoyl phosphatidylcholine (DPPC) enhanced pulmonary insulin delivery in rats, however, liposomes with dilauroyl, dimyristoyl, distearoyl or dioleoyl phosphatidylcholine did not. Liposomes with DPPC also enhanced the in vitro permeation of FITC dextran (Mw 4400, FD-4) through the calu-3 cell monolayer by reducing the transepithelial electrical resistance and did not harm lung tissues in rats. These findings suggest that liposomes with DPPC enhance pulmonary insulin delivery by opening the epithelial cell space in the pulmonary mucosa not mucosal cell damage. Liposomes with DPPC could be useful as a pulmonary delivery system for peptide and protein drugs.

  8. Potential Effect of Liposomes and Liposome-Encapsulated Botulinum Toxin and Tacrolimus in the Treatment of Bladder Dysfunction. (United States)

    Janicki, Joseph J; Chancellor, Michael B; Kaufman, Jonathan; Gruber, Michele A; Chancellor, David D


    Bladder drug delivery via catheter instillation is a widely used treatment for recurrence of superficial bladder cancer. Intravesical instillation of liposomal botulinum toxin has recently shown promise in the treatment of overactive bladder and interstitial cystitis/bladder pain syndrome, and studies of liposomal tacrolimus instillations show promise in the treatment of hemorrhagic cystitis. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core that can encapsulate hydrophilic and hydrophobic drug molecules to be delivered to cells via endocytosis. This review will present new developments on instillations of liposomes and liposome-encapsulated drugs into the urinary bladder for treating lower urinary tract dysfunction.

  9. Study on Leakage of Sesame (Sesamum indicum L. and Coconut (Cocos nucifera L. Liposomes

    Directory of Open Access Journals (Sweden)

    Dwi Hudiyanti


    Full Text Available Leakage phenomena on sesame (Sesamum indicum L. and coconut (Cocos nucifera L. liposomes has been studied to evaluate their ability as drug delivery materials. Permeation of carboxyfluorescein through the liposomes with and without added cholesterol was examined. Sesame liposomes release carboxyfluorescein less than coconut liposomes in all circumstances. Sesame liposomes save about 50% of payload after 17 hours of storage while coconut liposomes only 10%. Addition of cholesterol has increase storage capability of all liposomes. The sesame-cholesterol and coconut-cholesterol liposomes save greater amount of payload compare to the original. Sesame liposomes have better potency as drug delivery systems.

  10. Prospects of liposomes using for creating of new forms of the medicinal and preventive preparations

    Directory of Open Access Journals (Sweden)

    M. A. Kisjakova


    Full Text Available Information on the structure, physical and chemical characteristics of the phospholipid vesicles (liposomes – the effective natural drug delivery system is presented. Types of liposomes, procedures of its productions, penetration mechanisms into cells and functional features of liposomal drugs are described. Data on production of liposomes with lactobacilli acellular homogenates and the methods of the liposomes structure control asre demonstrated.

  11. Predicting the influence of liposomal lipid composition on liposome size, zeta potential and liposome-induced dendritic cell maturation using a design of experiments approach. (United States)

    Soema, Peter C; Willems, Geert-Jan; Jiskoot, Wim; Amorij, Jean-Pierre; Kersten, Gideon F


    In this study, the effect of liposomal lipid composition on the physicochemical characteristics and adjuvanticity of liposomes was investigated. Using a design of experiments (DoE) approach, peptide-containing liposomes containing various lipids (EPC, DOPE, DOTAP and DC-Chol) and peptide concentrations were formulated. Liposome size and zeta potential were determined for each formulation. Moreover, the adjuvanticity of the liposomes was assessed in an in vitro dendritic cell (DC) model, by quantifying the expression of DC maturation markers CD40, CD80, CD83 and CD86. The acquired data of these liposome characteristics were successfully fitted with regression models, and response contour plots were generated for each response factor. These models were applied to predict a lipid composition that resulted in a liposome with a target zeta potential. Subsequently, the expression of the DC maturation factors for this lipid composition was predicted and tested in vitro; the acquired maturation responses corresponded well with the predicted ones. These results show that a DoE approach can be used to screen various lipids and lipid compositions, and to predict their impact on liposome size, charge and adjuvanticity. Using such an approach may accelerate the formulation development of liposomal vaccine adjuvants.

  12. Properties of liposomal membranes containing lysolecithin. (United States)

    Kitagawa, T; Inoue, K; Nojima, S


    Liposomes have been prepared with lysolecithin (1-acyl-sn-3-glycerylphosphorylcholine), egg lecithin (3-sn-phosphatidylcholine), dicetyl phosphate, and cholesterol. The ability to function as a barrier to the diffusion of glucose marker and the sensitivities of the liposomes to hypotonic treatment and other reagents which modified the permeability were examined. Generally, lysolecithin incorporation decreased the effectiveness of the membranes as a barrier to glucose and made the membranes more "osmotically fragile." Cholesterol incorporation counteracted the effect of incorporated lysolecithin. The more cholesterol incorporated into liposomes, the more lysolecthin could be incorporated into the membrane without loss of function as a barrier. With more than 50 mole% of colesterol, lysolecithin alone could form membranes which were practically impermeable to glucose. The hemolytic activity of lysolecithin was affected by mixing with various lecithins or cholesterol. Liposomes containing lysolecithin, which have the ability to trap glucose marker, showed poor hemolytic activity, while lipid micelles with lysolecithin (which could trap little glucose) showed almost the same hemolytic activity as lysolecithin itself. There seems to be a close correlation between hemolytic activity and barrier function of lipid micelles.

  13. Influence of the Encapsulation Efficiency and Size of Liposome on the Oral Bioavailability of Griseofulvin-Loaded Liposomes (United States)

    Ong, Sandy Gim Ming; Ming, Long Chiau; Lee, Kah Seng; Yuen, Kah Hay


    The objective of the present study was to investigate the influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Griseofulvin-loaded liposomes with desired characteristics were prepared from pro-liposome using various techniques. To study the effect of encapsulation efficiency, three preparations of griseofulvin, namely, griseofulvin aqueous suspension and two griseofulvin-loaded liposomes with different amounts of griseofulvin encapsulated [i.e., F1 (32%) and F2(98%)], were administered to rats. On the other hand, to study the effect of liposome size, the rats were given three different griseofulvin-loaded liposomes of various sizes, generated via different mechanical dispersion techniques [i.e., FTS (142 nm), MS (357 nm) and NS (813 nm)], but with essentially similar encapsulation efficiencies (about 93%). Results indicated that the extent of bioavailability of griseofulvin was improved 1.7–2.0 times when given in the form of liposomes (F1) compared to griseofulvin suspension. Besides that, there was an approximately two-fold enhancement of the extent of bioavailability following administration of griseofulvin-loaded liposomes with higher encapsulation efficiency (F2), compared to those of F1. Also, the results showed that the extent of bioavailability of liposomal formulations with smaller sizes were higher by approximately three times compared to liposomal formulation of a larger size. Nevertheless, a further size reduction of griseofulvin-loaded liposome (≤400 nm) did not promote the uptake or bioavailability of griseofulvin. In conclusion, high drug encapsulation efficiency and small liposome size could enhance the oral bioavailability of griseofulvin-loaded liposomes and therefore these two parameters deserve careful consideration during formulation. PMID:27571096

  14. Influence of the Encapsulation Efficiency and Size of Liposome on the Oral Bioavailability of Griseofulvin-Loaded Liposomes

    Directory of Open Access Journals (Sweden)

    Sandy Gim Ming Ong


    Full Text Available The objective of the present study was to investigate the influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Griseofulvin-loaded liposomes with desired characteristics were prepared from pro-liposome using various techniques. To study the effect of encapsulation efficiency, three preparations of griseofulvin, namely, griseofulvin aqueous suspension and two griseofulvin-loaded liposomes with different amounts of griseofulvin encapsulated [i.e., F1 (32% and F2(98%], were administered to rats. On the other hand, to study the effect of liposome size, the rats were given three different griseofulvin-loaded liposomes of various sizes, generated via different mechanical dispersion techniques [i.e., FTS (142 nm, MS (357 nm and NS (813 nm], but with essentially similar encapsulation efficiencies (about 93%. Results indicated that the extent of bioavailability of griseofulvin was improved 1.7–2.0 times when given in the form of liposomes (F1 compared to griseofulvin suspension. Besides that, there was an approximately two-fold enhancement of the extent of bioavailability following administration of griseofulvin-loaded liposomes with higher encapsulation efficiency (F2, compared to those of F1. Also, the results showed that the extent of bioavailability of liposomal formulations with smaller sizes were higher by approximately three times compared to liposomal formulation of a larger size. Nevertheless, a further size reduction of griseofulvin-loaded liposome (≤400 nm did not promote the uptake or bioavailability of griseofulvin. In conclusion, high drug encapsulation efficiency and small liposome size could enhance the oral bioavailability of griseofulvin-loaded liposomes and therefore these two parameters deserve careful consideration during formulation.

  15. Liposomal Encapsulated Rhodomyrtone: A Novel Antiacne Drug

    Directory of Open Access Journals (Sweden)

    Julalak Chorachoo


    Full Text Available Rhodomyrtone isolated from the leaves of Rhodomyrtus tomentosa possesses antibacterial, anti-inflammatory, and anti-oxidant activities. Since rhodomyrtone is insoluble in water, it is rather difficult to get to the target sites in human body. Liposome exhibited ability to entrap both hydrophilic and hydrophobic compounds and easily penetrate to the target site. The present study aimed to develop a novel liposomal encapsulated rhodomyrtone formulations. In addition, characterization of liposome, stability profiles, and their antiacne activity were performed. Three different formulations of total lipid concentrations 60, 80, and 100 μmol/mL were used. Formulation with 60 μmol/mL total lipid (phosphatidylcholine from soybean and cholesterol from lanolin in 4 : 1, w/w exhibited the highest rhodomyrtone encapsulation efficacy (65.47 ± 1.7%, average particle size (209.56 ± 4.8 nm, and ζ-potential (–41.19 ± 1.3 mV. All formulations demonstrated good stability when stored for 2 months in dark at 4°C as well as room temperature. Minimal inhibitory concentration and minimal bactericidal concentration values of liposomal formulation against 11 clinical bacterial isolates and reference strains ranged from 1 to 4 and from 4 to 64 μg/mL, respectively, while those of rhodomyrtone were 0.25–1 and 0.5–2 μg/mL, respectively. The MIC and MBC values of liposome formulation were more effective than topical drugs against Staphylococcus aureus and Staphylococcus epidermidis.

  16. Effect of chitosan coating on the characteristics of DPPC liposomes

    Directory of Open Access Journals (Sweden)

    Mohsen M. Mady


    Full Text Available Because it is both biocompatible and biodegradable, chitosan has been used to provide a protective capsule in new drug formulations. The present work reports on investigations into some of the physicochemical properties of chitosan-coated liposomes, including drug release rate, transmission electron microscopy (TEM, zeta potential and turbidity measurement. It was found that chitosan increases liposome stability during drug release. The coating of DPPC liposomes with a chitosan layer was confirmed by electron microscopy and the zeta potential of liposomes. The coating of liposomes by chitosan resulted in a marginal increase in the size of the liposomes, adding a layer of (92 ± 27.1 nm. The liposomal zeta potential was found to be increasingly positive as chitosan concentration increased from 0.1% to 0.3% (w/v, before stabilising at a relatively constant value. Turbidity studies revealed that the coating of DPPC liposomes with chitosan did not significantly modify the main phase transition temperature of DPPC at examined chitosan concentrations. The appropriate combination of liposomal and chitosan characteristics may produce liposomes with specific, prolonged and controlled release.

  17. Bladder uptake of liposomes after intravesical administration occurs by endocytosis.

    Directory of Open Access Journals (Sweden)

    Bharathi Raja Rajaganapathy

    Full Text Available Liposomes have been used therapeutically and as a local drug delivery system in the bladder. However, the exact mechanism for the uptake of liposomes by bladder cells is unclear. In the present study, we investigated the role of endocytosis in the uptake of liposomes by cultured human UROtsa cells of urothelium and rat bladder. UROtsa cells were incubated in serum-free media with liposomes containing colloidal gold particles for 2 h either at 37°C or at 4°C. Transmission Electron Microscopy (TEM images of cells incubated at 37°C found endocytic vesicles containing gold inside the cells. In contrast, only extracellular binding was noticed in cells incubated with liposomes at 4°C. Absence of liposome internalization at 4°C indicates the need of energy dependent endocytosis as the primary mechanism of entry of liposomes into the urothelium. Flow cytometry analysis revealed that the uptake of liposomes at 37°C occurs via clathrin mediated endocytosis. Based on these observations, we propose that clathrin mediated endocytosis is the main route of entry for liposomes into the urothelial layer of the bladder and the findings here support the usefulness of liposomes in intravesical drug delivery.

  18. Stimuli-Responsive Liposomes for Controlled Drug Delivery

    KAUST Repository

    Li, Wengang


    Liposomes are promising drug delivery vesicles due to their biodegradibility, large volume and biocompatibility towards both hydrophilic and hydrophobic drugs. They suffer, however, from poor stability which limits their use in controlled delivery applications. Herein, a novel method was devised for modification of liposomes with small molecules, polymers or nanoparticles to afford stimuli responsive systems that release on demand and stay relatively stable in the absence of the trigger.. This dissertation discusses thermosensitive, pH sensitive, light sensitive and magnetically triggered liposomes that have been prepared for controlled drug delivery application. RAFT polymerization was utilized for the preparation of thermosensitive liposomes (Cholesterol-PNIPAm) and acid-labile liposomes (DOPE-PAA). With low Mw Cholesterol-PNIPAm, the thermosensitive liposomes proved to be effective for controlled release and decreased the cytotoxicity of PNIPAm by eliciting the polymer doses. By crosslinking the DOPE-PAA on liposome surface with acid-labile diamine linkers, DOPE-PAA liposomes were verified to be sensitive at low pH. The effects of polymer structures (linear or hyperbranched) have also been studied for the stability and release properties of liposomes. Finally, a dual-responsive Au@SPIO embedded liposome hybrid (ALHs) was prepared with light-induced “on-and-off” function by photo-thermal process (visible light) and instant release properties triggered by alternating magnetic field, respectively. The ALH system would be further applied into the cellular imaging field as MRI contrast agent.

  19. Preparation and evaluation of liposomal formulations of tropicamide for ocular delivery. (United States)

    Nagarsenker, M S; Londhe, V Y; Nadkarni, G D


    Tropicamide, a mydriatic, cycloplegic drug was entrapped in liposomes. Liposomes were investigated by laser counting studies, transmission electron microscopy and differential scanning calorimetry for characterization. The precorneal clearance of liposomes was compared with solution by gamma-scintigraphy in the rabbit. The neutral liposomes failed to demonstrate significant enhancement in precorneal retention in comparison with aqueous solution. The potential of liposomes as an ophthalmic drug delivery system was investigated by comparing pupil dilatory effect of tropicamide by topical instillation, in the rabbit eye, of the solution and various drug-loaded liposomal forms, i.e. neutral liposomes, positively charged liposomes and neutral liposomes dispersed in 0.25% (w/v) polycarbophil gel. The positively charged liposomal formulation and liposomes dispersed in polycarbophil gel were found to be more effective than neutral liposomal dispersion when data were statistically treated at the 5% level of significance.

  20. Analysis of liposomes using asymmetrical flow field-flow fractionation

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Decker, Christiane; Fahr, Alfred


    Liposomes composed of dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol were analyzed by asymmetrical flow field-flow fractionation coupled with multi-angle laser light scattering. In addition to evaluation of fractionation conditions (flow conditions, sample mass, carrier liquid......), radiolabeled drug-loaded liposomes were used to determine the liposome recovery and a potential loss of incorporated drug during fractionation. Neither sample concentration nor the cross-flow gradient distinctly affected the size results but at very low sample concentration (injected mass 5 μg) the fraction...... of larger vesicles was underestimated. Imbalance in the osmolality between the inner and outer aqueous phase resulted in liposome swelling after dilution in hypoosmotic carrier liquids. In contrast, liposome shrinking under hyperosmotic conditions was barely visible. The liposomes themselves eluted...

  1. Liposomal amphotericin B for the treatment of visceral leishmaniasis. (United States)

    Bern, Caryn; Adler-Moore, Jill; Berenguer, Juan; Boelaert, Marleen; den Boer, Margriet; Davidson, Robert N; Figueras, Concepcion; Gradoni, Luigi; Kafetzis, Dimitris A; Ritmeijer, Koert; Rosenthal, Eric; Royce, Catherine; Russo, Rosario; Sundar, Shyam; Alvar, Jorge


    During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). The World Health Organization convened a workshop to review current knowledge and to develop guidelines for liposomal amphotericin B use for VL. In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia, the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferential pricing for nonprofit groups in East Africa. Clinical trials and experience demonstrate high efficacy and low toxicity for liposomal amphotericin B (total dose, 20 mg/kg) in immunocompetent patients with VL. Combination trials in areas with antileishmanial drug resistance, and treatment and secondary prophylaxis trials in VL-human immunodeficiency virus-coinfected patients, are important to safeguard the current armamentarium and to optimize regimens. The public health community should work to broaden access to preferential liposomal amphotericin B pricing by public sector VL treatment programs.

  2. Liposomal delivery of radionuclides for cancer diagnostics and radiotherapy

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa

    , as the use of positron emission tomography (PET) scanners for molecular and diagnostic imaging has become more attractive. Furthermore, the importance of molecular and diagnostic imaging in nanotechnology has also been recognized, and significant research has been conducted on radiolabeled liposomes...... for scintigraphy and single photon emission computed tomography (SPECT) imaging. Preclinical as well as clinical SPECT studies on radiolabeled liposomes have contributed with valuable information on the pharmacokinetics of liposomes during several liposomal drug developments. SPECT has lower detection sensitivity......, an in vivo study is presented, where passive tumor accumulation of 64Cu loaded liposomes (64Cu-liposomes) in tumor-bearing mice was quantified directly by PET and computed tomography (CT) imaging. Furthermore, Article I present an evaluation and quantitative measurement of the biodistribution of 64Cu...

  3. Advances and Challenges of Liposome Assisted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Lisa eSercombe


    Full Text Available The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented.

  4. Development of monodispersed and functional magnetic polymeric liposomes via simple liposome method

    Energy Technology Data Exchange (ETDEWEB)

    Liang Xiaofei; Wang Hanjie [Tianjin University and Tianjin Key Laboratory of Composites and Functional Materials, Institute of Nanobiotechnology, School of Materials Science and Engineering (China); Jiang Xinguo [Fudan University, School of Pharmacy (China); Chang Jin, E-mail: [Tianjin University and Tianjin Key Laboratory of Composites and Functional Materials, Institute of Nanobiotechnology, School of Materials Science and Engineering (China)


    We are reporting a simple and rapid method to prepare superparamagnetic, controlled size, and monodispersed magnetic cationic polymeric liposomes (MCPL) by octadecyl quaternized carboxymethyl chitosan (OQCMC) and cholesterol. The whole process is only about 25 min with simple thin-film dispersion and solvent evaporation method. Hydrophilic magnetic nanoparticles (LM) and hydrophobic magnetic nanoparticles (BM) can be encapsulated into these cationic polymeric liposomes, simultaneously or respectively. A model hydrophobic drug indomethacin can be successfully filled in MCPL with high drug loading capacity 22%. MCPL encapsulating BM also showed strong DNA (pEGFP) binding ability. Drug-loaded MCPL have a long and controlled sustained release profile by changing the number of polymeric lipid layer. These functional MCPL nanospheres can be allowed to serve as ideal candidates for many biomedical applications.Graphical AbstractA simple and rapid liposome method was reported to prepare superparamagnetic, controlled size, and monodispersed magnetic cationic polymeric liposomes (MCPL) by polymeric surfactant, octadecyl quaternized carboxymethyl chitosan (OQCMC), and cholesterol. Hydrophilic Fe{sub 3}O{sub 4} ferrofluid and hydrophobic magnetic nanoparticles can be encapsulated into these cationic polymeric liposomes, simultaneously or respectively. Hydrophobic drug indomethacin can be encapsulated into this MCPL with high encapsulating efficiency and with controlled release profile by changing the number of polymeric lipid layer.

  5. Liposome clusters with shear stress-induced membrane permeability. (United States)

    Yoshimoto, Makoto; Tamura, Ryota; Natsume, Tomotaka


    Clusters of negatively charged liposomes were prepared by the addition of Ca(2+) and characterized in their structure and membrane permeability under shear stress. The liposomes mainly used were composed of zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 20 mol% negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and 30 mol% cholesterol. The liposomes with mean diameter of 193 nm were aggregated into the clusters with a distribution peak at about 1.5 μm in the 50mM Tris buffer solution of pH 8.5 at the lipid and Ca(2+) concentrations of 1.0mM and 40 mM, respectively. More than 90% of liposomes were redispersed at the Ca(2+) concentration of 80 mM. POPG-rich liposomes (POPC/POPG/cholesterol=5:65:30 [lipid]=1.0mM) were irreversibly aggregated at [Ca(2+)]≥ 10 mM, indicating the significant contribution of POPC to the reversible clustering of liposomes. The membranes of liposome clusters were impermeable to 5(6)-carboxyfluorescein (CF) in the static liquid system at 25°C due to the decrease in specific surface area of the liposomal system. In the shear flow, in clear contrast, continuous membrane permeation of CF was observed at the shear rate of 1.5 × 10(3)s(-1), exhibiting comparable membrane permeability to the non-clustered liposomes. The theoretical analysis of modified DLVO potential indicated that liposome membranes were not in contact with each other within the clusters. Therefore, the liposome clusters are structurally flexible under the applied shear stress, providing sufficient lipid membrane-water interfacial area for the permeation of CF. The results obtained would be important to control the formation of liposome clusters and their permeabilization for biochemical and biomedical applications.

  6. Liposomes: structure, properties and methods of curative administration in organism

    Directory of Open Access Journals (Sweden)

    M. A. Kisyakova


    Full Text Available A review of data from scientific sources, devoted to problems of liposomes’ structure, properties and processes of formation was made. Advantages of liposomes used for medical purposes are shown. Methods of liposomes administration in an organism are characterised. Data on mechanisms of interaction between liposomes and cells, peculiarities of liposomes’ lipids composition and dependence of its tropism to definite organs and tissues are generalised.

  7. Characterization of sterically stabilized cisplatin liposomes by nuclear magnetic resonance. (United States)

    Peleg-Shulman, T; Gibson, D; Cohen, R; Abra, R; Barenholz, Y


    Extensive scientific efforts are directed towards finding new and improved platinum anticancer agents. A promising approach is the encapsulation of cisplatin in sterically stabilized, long circulating, PEGylated 100 nm liposomes. This liposomal cisplatin (STEALTH cisplatin, formerly known as SPI-77) shows excellent stability in plasma and has a longer circulation time, greater efficacy and lower toxicity than much free cisplatin. However, so far, the physicochemical characterization of STEALTH cisplatin has been limited to size distribution, drug-to-lipid ratio and stability. Information on the physical state of the drug in the liposome aqueous phases and the drug's interaction with the liposome membrane has been lacking. This study was aimed at filling this gap. We report a multinuclear NMR study in which several techniques have been used to assess the physical nature of cisplatin in liposomal formulations and if and to what extent the drug affects the liposome phospholipids. Since NMR detects only the soluble cisplatin in the liposomes and not the insoluble drug, combining NMR and atomic absorption data enables one to determine how much of the encapsulated drug is soluble in the intraliposomal aqueous phase. Our results indicate that almost all of the cisplatin remains intact during the loading process, and that the entire liposomal drug is present in a soluble form in the internal aqueous phase of the liposomes.

  8. Liposomes and MTT cell viability assay: an incompatible affair. (United States)

    Angius, Fabrizio; Floris, Alice


    The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is commonly used to evaluate the cytotoxicity potential of drugs vehicled by liposomes. However, liposome delivering drugs could produce inconsistent values of MTT absorbance. On the basis of previous experiments demonstrating the MTT affinity for lipid droplets, this paper aims to show that empty-liposomes interfere, per se, on MTT assay due to its lipidic nature. This brings into question the use of MTT testing cytotoxicity when liposomes are involved in delivering drugs.

  9. Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries. (United States)

    Jain, Pritesh P; Leber, Regina; Nagaraj, Chandran; Leitinger, Gerd; Lehofer, Bernhard; Olschewski, Horst; Olschewski, Andrea; Prassl, Ruth; Marsh, Leigh M


    Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud's phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy.

  10. Application of long-circulating liposomes to cancer photodynamic therapy. (United States)

    Oku, N; Saito, N; Namba, Y; Tsukada, H; Dolphin, D; Okada, S


    Photodynamic therapy (PDT) as a cancer treatment is notable for its quite low side effects in comparison with those of chemotherapy and radiotherapy. However, the accumulation of porphyrin derivatives used in PDT into tumor tissues is rather low. Since long-circulating liposomes are known to accumulate passively into tumor tissues, we liposomalized a porphyrin derivative, benzoporphyrin derivative monoacid ring A (BPD-MA), and used these liposomes to investigate the usefulness of PDT for tumor-bearing mice. BPD-MA was liposomalized into glucuronate-modified liposomes, which are known to be long-circulating. These liposomes were injected i.v. into Balb/c mice bearing Meth A sarcoma, and tumor regression and survival time were monitored after irradiation with laser light. Tumor regression and complete curing of tumor (80% cure rate by the treatment with 6 mg/kg BPD-MA) were observed when long circulating liposomalized BPD-MA was injected and laser-irradiated. In contrast, only a 20% cure rate was obtained when the animals were treated with BPD-MA solution or BPD-MA entrapped in conventional liposomes. These results suggest that a long-circulating liposomal formulation of photo-sensitive agents is useful for PDT.

  11. Paramagnetic Liposome Nanoparticles for Cellular and Tumour Imaging

    Directory of Open Access Journals (Sweden)

    Nazila Kamaly


    Full Text Available In this review we discuss the development of paramagnetic liposomes incorporating MRI contrast agents and show how these are utilized in cellular imaging in vitro. Bi-functional, bi-modal imaging paramagnetic liposome systems are also described. Next we discuss the upgrading of paramagnetic liposomes into bi-modal imaging neutral nanoparticles for in vivo imaging applications. We discuss the development of such systems and show how paramagnetic liposomes and imaging nanoparticles could be developed as platforms for future multi-functional, multi-modal imaging theranostic nanodevices tailor-made for the combined imaging of early stage disease pathology and functional drug delivery.

  12. Liposomal extended-release bupivacaine for postsurgical analgesia

    National Research Council Canada - National Science Library

    Lambrechts, Mark; O'Brien, Michael J; Savoie, Felix H; You, Zongbing


    ..., inguinal hernia repair, total knee arthroplasty, and augmentation mammoplasty. However, like other bupivacaine formulations, the liposomal extended-release bupivacaine does have some side effects...

  13. A study on zeta potential and dielectric constant of liposomes. (United States)

    Labhasetwar, V; Mohan, M S; Dorle, A K


    Zeta potential and dielectric constant of the liposomes were measured to study the effect of some of the formulation factors and in vitro ageing. Sonication affects zeta potential and dielectric constant of the liposomes. The ageing study showed an increase in the dielectric constant and zeta potential of liposomes at different storage temperatures. These two electrical parameters could be useful in studying structural alterations in liposomal vesicles and system as a function of different conditions. Particle size distribution and optical density were also measured, for comparison.

  14. Phase structure of liposome in lipid mixtures. (United States)

    Zhang, Tianxi; Li, Yuzhuo; Mueller, Anja


    Gas microbubbles present in ultrasound imaging contrast agents are stabilized by lipid aggregates that typically contain a mixture of lipids. In this study, the phase structure of the lipid mixtures that contained two or three lipids was investigated using three different methods: dynamic light scattering, (1)H NMR, and microfluidity measurements with fluorescence probes. Three lipids that are commonly present in imaging agents (DPPC, DPPE-PEG, and DPPA) were used. Two types of systems, two-lipid model systems and simulated imaging systems were investigated. The results show that liposomes were the dominant aggregates in all the samples studied. The polar PEG side chains from the PEGylated lipid lead to the formation of micelles and micellar aggregates in small sizes. In the ternary lipid systems, almost all the lipids were present in bilayers with micelles absent and free lipids at very low concentration. These results suggest that liposomes, not micelles, contribute to the stabilization of microbubbles in an ultrasound imaging contrast agent.

  15. Photodynamic action of hypocrellin A in liposomes

    Institute of Scientific and Technical Information of China (English)

    邹伟; 安静仪; 李滨; 蒋丽金


    Hypocrellin A (HA), a perylenequinone derivative, is an efficient phototherapeutic agent. When HA is incorporated into small unilamellar liposomes of egg phosphatidylcholine, it generates 1O2 as demonstrated by 9,10-diphenylanthracene (9,10-DPA) photobleaching and detection of nitroxide radicals with ESR. The 1O2 quantum yield measured is 0.80±0.02. On irradiation of oxygen-saturated solution of HA-liposomes, hydroxyl radical OH is detected using DMPO as the ESR spin trapping agent. Hydroxyl radical is derived from superoxide radical anion O2-. The electron transfer reaction is also studied in deaerated solution. The results suggest that the photodynamic action of HA in lipid membranes proceeds via both Type I and Type II reactions.

  16. Pegylated liposomal doxorubicin in ovarian cancer


    Matei, Daniela


    Robert Strother1,2, Daniela Matei1–51Department of Medicine, 2Indiana University Melvin and Bren Simon Cancer Center, 3Department of Obstetrics and Gynecology, 4Department of Biochemistry and Molecular Biology, 5VA Roudebush Hospital Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN, 46202Abstract: The encapsulation of doxorubicin in a pegylated liposomal matrix led to a reformulated agent with a different toxicity profile and improved clinical utility. Lip...

  17. Liposomes as lubricants: beyond drug delivery. (United States)

    Goldberg, Ronit; Klein, Jacob


    In this paper we review recent work (Goldberg et al., 2011a,b) on a new use for phosphatidylcholine liposomes: as ultra-efficient boundary lubricants at up to the highest physiological pressures. Using a surface force balance, we have measured the normal and shear interactions as a function of surface separation between layers of hydrogenated soy phophatidylcholine (HSPC) small unilamellar vesicles (SUVs) adsorbed from dispersion, at both pure water and physiologically high salt concentrations of 0.15 M NaNO(3). Cryo-Scanning Electron Microscopy shows each surface to be coated by a close-packed HSPC-SUV layer with an over-layer of liposomes on top. The shear forces reveal strikingly low friction coefficients down to 2×10(-5) in pure water system or 6×10(-4) in the 150 mM salt system, up to contact pressures of at least 12 MPa (pure water) or 6 MPa (high salt), comparable with those in the major joints. This low friction is attributed to the hydration lubrication mechanism arising from rubbing of the highly hydrated phosphocholine-headgroup layers exposed at the outer surface of each liposome, and provides support for the conjecture that phospholipids may play a significant role in biological lubrication.

  18. Liposomal nanoparticles as a drug delivery vehicle against osteosarcoma (United States)

    Dhule, Santosh Subhashrao

    The delivery of curcumin, a broad-spectrum anticancer drug, has been explored in the form of liposomal nanoparticles to treat osteosarcoma (OS). Curcumin is water insoluble and an effective delivery route is through encapsulation in cyclodextrins followed by a second encapsulation in liposomes. Liposomal curcumin's potential was evaluated against cancer models of mesenchymal (OS) and epithelial origin (breast cancer). The resulting 2-Hydroxypropyl-gamma-cyclodextrin/curcumin - liposome complex shows promising anticancer potential both in vitro and in vivo against KHOS OS cell line and MCF-7 breast cancer cell line. An interesting aspect is that liposomal curcumin initiates the caspase cascade that leads to apoptotic cell death in vitro in comparison with DMSO-curcumin induced autophagic cell death. In addition, the efficiency of the liposomal curcumin formulation was confirmed in vivo using a xenograft OS model. Curcumin-loaded gamma-cyclodextrin liposomes indicate significant potential as delivery vehicles for the treatment of cancers of different tissue origin. The second part of this study examines the anti-tumor potential of curcumin and C6 ceramide (C6) against osteosarcoma cell lines when both are encapsulated in the bilayer of liposomal nanoparticles. Curcumin in combination with C6 showed 1.5 times enhanced cytotoxic effect in the case of MG-63 and KHOS OS cell lines, in comparison with systems with curcumin alone. Interestingly, C6-curcumin liposomes were found to be less toxic on untransformed human cells in comparison to OS cell lines. In addition, cell cycle assays on a KHOS cell line after treatment revealed that curcumin only liposomes induced G 2/M arrest by upregulation of cyclin B1, while C6 only liposomes induced G1 arrest by downregulation of cyclin D1. C6-curcumin liposomes induced G2/M arrest and showed a combined effect in the expression levels of cyclin D1 and cyclin B1. Using pegylated liposomes to increase the plasma half-life and tagging

  19. Preliminary Studies on X-Ray-sensitive Liposome

    Institute of Scientific and Technical Information of China (English)

    MENG Fan-xu; XU Hua-ping; QI Yan-fei; XU Kun; SONG Xiu-ling; NIU Shu; LI Juan


    The synthesis of a new type of X-ray-sensitive compound “di-(1-hydroxylundecyl)diselenide” and its application in the preparation of a new type of liposome with X-ray sensitivity was reported.This new liposome was synthesized to encapsulate doxorubicin hydrochloride(Dox),with its physical and chemical properties,stability,and radiation sensitivity determined.Based on the pH-gradient method,liposomal Dox was prepared via ultrasonic emulsification and then purified on a Sephadex G50 mini-column.UV spectrophotometry and liquid chromatography were used to detect the encapsulation efficiency and radiation sensitivity of the Dox-loaded liposome.The results show that through changes in release rate,this liposome shows a relative radiosensitivity.In terms of radiation sensitivity,the drug leak rate of the X-ray-sensitive Dox-loaded liposome increased gradually and peaked at 65.4% under the X-ray radiation of a dose of 10 Gy or more than 10 Gy,which is significantly different from that of ordinary liposomes.Meanwhile,X-ray-sensitive Dox-loaded liposome has a good dispersion stability,with an average particle size of approximate 120 nm.The efficiency of this liposome encapsulating Dox was 75.84%,slightly lower than that of ordinary liposomes.The X-ray-sensitive Dox-loaded liposome exhibited suspension stability within 30 d of storage at 4 ℃,without visible precipitation.Di-(1-hydroxylundecyl)diselenide is safe and noncytotoxic and compared with those of synthetic phospholipids its synthesis is low cost and does not require complex conditions.

  20. Polyelectrolyte stabilized multilayered liposomes for oral delivery of paclitaxel

    DEFF Research Database (Denmark)

    Jain, Sanyog; Kumar, Dinesh; Swarnakar, Nitin K


    Paclitaxel (PTX) loaded layersome formulations were prepared using layer-by-layer assembly of the polyelectrolytes over liposomes. Stearyl amine was utilized to provide positive charge to the liposomes, which were subsequently coated with anionic polymer polyacrylic acid (PAA) followed by coating...

  1. Liposomal drug delivery systems: from concept to clinical applications. (United States)

    Allen, Theresa M; Cullis, Pieter R


    The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as drug delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of drugs. These advances have led to numerous clinical trials in such diverse areas as the delivery of anti-cancer, anti-fungal and antibiotic drugs, the delivery of gene medicines, and the delivery of anesthetics and anti-inflammatory drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future.

  2. Enzyme sensitive liposomes in chemotherapy and potentiation of immunotherapy

    DEFF Research Database (Denmark)

    Østrem, Ragnhild Garborg

    liposome system is evaluated. Here cationic liposomes are engineered with an MMP cleavable PEG construct, aimed at shedding the PEG layer upon encounter with cancer expressed MMP enzymes, leading to exposure of the cationic charge and enhanced uptake in cancer cells. It is demonstrated that although...

  3. Immunological Effect of Subunit Influenza Vaccine Entrapped by Liposomes

    Institute of Scientific and Technical Information of China (English)



    Objective To elevate the immunological effect of subunit influenza vaccine in infants and aged people (over 60) using liposomal adjuvant in the context of its relatively low immunity and to investigate the relation between vaccine antigens and liposomal characteristics. Methods Several formulations of liposomal subunit influenza vaccine were prepared. Their relevant characteristics were investigated to optimize the preparation method. Antisera obtained from immunizinged mice were used to evaluate the antibody titers of various samples by HI and ELISA. Results Liposomal trivalent influenza vaccine prepared by film evaporation in combinedation with freeze-drying significantly increased its immunological effect in SPF Balb/c mice. Liposomal vaccine stimulated the antibody titer of H3N2, H1N1, and B much stronger than conventional influenza vaccine. As a result, liposomal vaccine (mean size: 4.5-5.5 μm, entrapment efficiency: 30%-40%) significantly increased the immunological effect of subunit influenza vaccine. Conclusion The immune effect of liposomal vaccine depends on different antigens, and enhanced immunity is not positively correlated with the mean size of liposome or its entrapped efficiency.

  4. Biodistribution of liposome-entrapped human gamma-globulin. (United States)

    García-Santana, María A; Duconge, Jorge; Sarmiento, María E; Lanio-Ruíz, María E; Becquer, María A; Izquierdo, Luís; Acosta-Domínguez, Armando


    The present study was aimed at the preparation and performance evaluation of Intacglobin-loaded liposomes for selective drug presentation to the lungs. Egg phosphatidylcholine- and cholesterol-based liposomes (1:1 and 1:0.25 mol/mol) were prepared by a dehydration-rehydration procedure. A tissue distribution study after single intranasal administration of 0.5 microCi 125I-Intacglobin-loaded liposomes was conducted in Balb/c mice. The efficiencies of drug entrapment (30%) and the average diameters did not differ significantly between the two liposome formulations. However, liposomes composed of an increased cholesterol amount showed a lower in vitro drug release rate. The airway penetration efficiency of the liposomal formulation was determined by the cumulative percentage of the dose reaching the lungs (AUC) and its sojourn time therein, and were 1.7- and 2.2-times higher compared with the plain 125I- Intacglobin solution-based formulation, respectively. A significantly greater (p<0.001) drug localization index after 24 h was found at the lungs in comparison with the other tissues (p<0.01), although similar values were detected between groups following administration of either liposomes or control solutions, despite the formulations attributes. In conclusion, it is suggested that longer Intacglobin exposure at the pulmonary region is observed after administration of the liposomal formulation. The results open future perspectives in assessing local passive immunization for the treatment of respiratory infectious diseases.

  5. Biophysical characterization of gold nanoparticles-loaded liposomes. (United States)

    Mady, Mohsen Mahmoud; Fathy, Mohamed Mahmoud; Youssef, Tareq; Khalil, Wafaa Mohamed


    Gold nanoparticles were prepared and loaded into the bilayer of dipalmitoylphosphatidylcholine (DPPC) liposomes, named as gold-loaded liposomes. Biophysical characterization of gold-loaded liposomes was studied by transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy as well as turbidity and rheological measurements. FTIR measurements showed that gold nanoparticles made significant changes in the frequency of the CH(2) stretching bands, revealing that gold nanoparticles increased the number of gauche conformers and create a conformational change within the acyl chains of phospholipids. The transmission electron micrographs (TEM) revealed that gold nanoparticles were loaded in the liposomal bilayer. The zeta potential of DPPC liposomes had a more negative value after incorporating of Au NPs into liposomal membranes. Turbidity studies revealed that the loading of gold nanoparticles into DPPC liposomes results in shifting the temperature of the main phase transition to a lower value. The membrane fluidity of DPPC bilayer was increased by loading the gold nanoparticles as shown from rheological measurements. Knowledge gained in this study may open the door to pursuing liposomes as a viable strategy for Au NPs delivery in many diagnostic and therapeutic applications.

  6. Slow fusion of liposomes composed of membrane-spanning lipids

    NARCIS (Netherlands)

    Elferink, MGL; vanBreemen, J; Konings, WN; Driessen, AJM; Wilschut, J; Elferink, Marieke G.L.


    The fusion characteristics of large unilamellar liposomes composed of bipolar tetraether lipids extracted from the thermophilic archaeon Sulfolobus acidocaldarius, was investigated. These lipids span the entire membrane and form single monolayer liposomes in aqueous media [Elferink, M.G.L., de Wit,

  7. Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging (United States)

    Kuijten, Maayke M. P.; Hannah Degeling, M.; Chen, John W.; Wojtkiewicz, Gregory; Waterman, Peter; Weissleder, Ralph; Azzi, Jamil; Nicolay, Klaas; Tannous, Bakhos A.


    Liposomes are spherical, self-closed structures formed by lipid bilayers that can encapsulate drugs and/or imaging agents in their hydrophilic core or within their membrane moiety, making them suitable delivery vehicles. We have synthesized a new liposome containing gadolinium-DOTA lipid bilayer, as a targeting multimodal molecular imaging agent for magnetic resonance and optical imaging. We showed that this liposome has a much higher molar relaxivities r1 and r2 compared to a more conventional liposome containing gadolinium-DTPA-BSA lipid. By incorporating both gadolinium and rhodamine in the lipid bilayer as well as biotin on its surface, we used this agent for multimodal imaging and targeting of tumors through the strong biotin-streptavidin interaction. Since this new liposome is thermosensitive, it can be used for ultrasound-mediated drug delivery at specific sites, such as tumors, and can be guided by magnetic resonance imaging.

  8. Enhanced antitumor effect of novel dual-targeted paclitaxel liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Meng Shuyan; Su Bo; Li Wei; Ding Yongmei; Tang Liang; Zhou Wei; Song Yin; Li Heyan; Zhou Caicun, E-mail: [Cancer Institute of Tongji University School of Medicine, Shanghai Pulmonary Hospital, 507 Zhengmin Road, Shanghai (China)


    A novel dual-targeted peptide containing an alpha V integrins specific ligand and a neuropilin-1 specific motif was developed which showed an increased specific targeting affinity to tumors. Active dual-targeted liposomes were then produced with this peptide and exhibited greater binding activity than single-targeted liposomes in vitro. Paclitaxel entrapped in this formulation greatly increased the uptake of paclitaxel in the targeting cells and significantly suppressed the growth of HUVEC and A549 cells compared with general paclitaxel injections (Taxol) and single-targeted paclitaxel liposomes. The treatment of tumor xenograft models with dual-targeted paclitaxel liposomes also resulted in better tumor growth inhibition than any other treatment groups. Therefore, the dual-targeted paclitaxel liposomes prepared in the present study might be a more promising drug for cancer treatment. Furthermore, the dual-targeting approach may produce synergistic effects that can be applied in the development of new targeted drug delivery systems.

  9. Microfabrication of three-dimensional filters for liposome extrusion (United States)

    Baldacchini, Tommaso; Nuñez, Vicente; LaFratta, Christopher N.; Grech, Joseph S.; Vullev, Valentine I.; Zadoyan, Ruben


    Liposomes play a relevant role in the biomedical field of drug delivery. The ability of these lipid vesicles to encapsulate and transport a variety of bioactive molecules has fostered their use in several therapeutic applications, from cancer treatments to the administration of drugs with antiviral activities. Size and uniformity are key parameters to take into consideration when preparing liposomes; these factors greatly influence their effectiveness in both in vitro and in vivo experiments. A popular technique employed to achieve the optimal liposome dimension (around 100 nm in diameter) and uniform size distribution is repetitive extrusion through a polycarbonate filter. We investigated two femtosecond laser direct writing techniques for the fabrication of three-dimensional filters within a microfluidics chip for liposomes extrusion. The miniaturization of the extrusion process in a microfluidic system is the first step toward a complete solution for lab-on-a-chip preparation of liposomes from vesicles self-assembly to optical characterization.

  10. Interactions of a Photochromic Spiropyran with Liposome Model Membranes

    KAUST Repository

    Jonsson, Fabian


    The interactions between anionic or zwitterionic liposomes and a water-soluble, DNA-binding photochromic spiropyran are studied using UV/vis absorption and linear dichroism (LD) spectroscopy. The spectral characteristics as well as the kinetics of the thermal isomerization process in the absence and presence of the two different liposome types provide information about the environment and whether or not the spiropyran resides in the liposome membrane. By measuring LD on liposomes deformed and aligned by shear flow, further insight is obtained about interaction and binding geometry of the spiropyran at the lipid membranes. We show that the membrane interactions differ between the two types of liposomes used as well as the isomeric forms of the spiropyran photoswitch. © 2013 American Chemical Society.

  11. Calcipotriol delivery into the skin with PEGylated liposomes

    DEFF Research Database (Denmark)

    Knudsen, Nina Østergaard; Rønholt, Stine; Salte, Ragnhild Djønne


    The d-vitamin analogue calcipotriol is commonly used for topical treatment of psoriasis, but skin penetration is required for calcipotriol to reach its pharmacological target: the keratinocytes in the lower epidermis. Liposomes can enhance the delivery of drugs into the skin, but a major challenge...... for the development of dosage forms containing liposomes is to maintain the colloidal stability in the formulation. The purpose of this study was to investigate the effect of stabilising liposomes with the lipopolymer poly(ethylene glycol)-distearoylphosphoethanolamine (PEG-DSPE) on the physicochemical properties...... of the liposomes and the ability to deliver membrane-intercalated calcipotriol into the skin. Inclusion of 0.5, l and 5mol% PEG-DSPE in the membrane enhanced the colloidal stability of the liposomes without compromising the delivery of calcipotriol from the vehicle into excised pig skin. Calcipotriol...

  12. Characteristics of photosensitization of Pheophorbide a in liposomal media

    Institute of Scientific and Technical Information of China (English)

    杨红英; 李美芬; 张文庚; 赵红霞; 张志义


    Pheophorbide a (PPa), a decomposition product of chlorophyll a, is a photosensitizer. The photosensitization mechanisms (Type Ⅰ and Type Ⅱ) of PPa in simple buffer solutions and in buffer solutions containing double-layered DPPC liposomes have been studied using techniques of ESR, spin-trapping, spin-counteraction and laser flash photolysis. The results showed that adding DPPC liposomes to the buffer solution caused an increase of efficiency of generating 1O2 and PPa- by photoactivating PPa. The increase could be ascribed to the disaggregation of hydrophobic PPa caused by the addition of liposomes and the protective effect of liposomal media on the triplet state of PPa. It is concluded that the photosensitization of PPa in liposomal systems is different from that in simple aqueous solutions, and shows higher efficacy. The results will be useful to elucidating the mechanisms of photodynamic therapy of cancer.

  13. The hypoglycaemic response of diabetic rats to insulin-liposomes. (United States)

    Petkowicz, J; Byra, A; Szumiło, T


    We prepared insulin-liposomes using one combination of lipids including phosphatidylcholine (cholesterol) stearylamine, 7/2/1 (molar ratio). Non-sonicated liposomes (LMV) and sonicated liposomes (SUV) contained about 20% and 5% of insulin, respectively. Free insulin was removed from liposomes-associated insulin by ultracentrifugation, or ultrafiltration on Sepharose 6B column. Insulin preparations were administered parenterally and non-parenterally into male, Wistar rats with alloxan diabetes to produce the hypoglycaemia. In case of i.v. and s.c. routes of administration all preparations acted in the similar manner giving the clear hypoglycaemia after 2 h. When administered intragastrically only liposome insulin caused hypoglycaemia. In case of buccal and nasal routes of administration only SUV-insulin was effective.

  14. The Treatment of Breast Cancer Using Liposome Technology

    Directory of Open Access Journals (Sweden)

    Sarah Brown


    Full Text Available Liposome-based chemotherapeutics used in the treatment of breast cancer can in principle enhance the therapeutic index of otherwise unencapsulated anticancer drugs. This is partially attributed to the fact that encapsulation of cytotoxic agents within liposomes allows for increased concentrations of the drug to be delivered to the tumor site. In addition, the presence of the phospholipid bilayer prevents the encapsulated active form of the drug from being broken down in the body prior to reaching tumor tissue and also serves to minimize exposure of the drug to healthy sensitive tissue. While clinically approved liposome-based chemotherapeutics such as Doxil have proven to be quite effective in the treatment of breast cancer, significant challenges remain involving poor drug transfer between the liposome and cancerous cells. In this review, we discuss the recent advancements made in the development of liposome-based chemotherapeutics with respect to improved drug transfer for use in breast cancer therapy.

  15. Ultrasound triggered drug delivery with liposomal nested microbubbles. (United States)

    Wallace, N; Wrenn, S P


    When ultrasound contrast agent microbubbles are nested within a liposome, damage to the liposome membrane caused by both stable and inertial cavitation of the microbubble allows for release of the aqueous core of the liposome. Triggered release was not accomplished unless microbubbles were present within the liposome. Leakage was tested using fluorescence assays developed specifically for this drug delivery vehicle and qualitative measurements using an optical microscope. These studies were done using a 1 MHz focused ultrasound transducer while varying parameters including peak negative ultrasound pressure, average liposome diameter, and microbubble concentration. Two regimes exist for membrane disruption caused by cavitating microbubbles. A faster release rate, as well as permanent membrane damage are seen for samples exposed to high pressure (2.1-3.7 MPa). A slower release rate and dilation/temporary poration are characteristic of stable cavitation for low pressure studies (0.54-1.7 MPa).

  16. Liposomal dry powders as aerosols for pulmonary delivery of proteins. (United States)

    Lu, Dongmei; Hickey, Anthony J


    The purpose of this research was to develop liposomal dry powder aerosols for protein delivery. The delivery of stable protein formulations is essential for protein subunit vaccine delivery, which requires local delivery to macrophages in the lungs. Beta-glucuronidase (GUS) was used as a model protein to evaluate dry powder liposomes as inhaled delivery vehicles. Dimyristoyl phosphatylcholine:cholesterol (7:3) was selected as the liposome composition. The lyophilization of liposomes, micronization of the powders, aerosolization using a dry powder inhaler (DPI), and in vitro aerodynamic fine particle fraction upon collection in a twin-stage liquid impinger were evaluated. After lyophilization and jet-milling, the total amount of GUS and its activity, representing encapsulation efficiency and stability, were evaluated. The GUS amount and activity were measured and compared with freshly-prepared liposomes in the presence of mannitol, 43% of initial GUS amount, 29% of GUS activity after lyophilization and 36% of GUS amount, 22% of activity after micronization were obtained. Emitted doses from dry powder inhaler were 53%, 58%, 66%, and 73% for liposome powder:mannitol carrier ratios of 1:0, 1:4, 1:9, and 1:19. Fifteen percent of the liposome particles were less than 6.4 mum in aerodynamic diameter. The results demonstrate that milled liposome powders containing protein molecules can be aerosolized effectively at a fixed flow rate. Influences of different cryoprotectants on lyophilization of protein liposome formulations are reported. The feasibility of using liposomal dry powder aerosols for protein delivery has been demonstrated but further optimization is required in the context of specific therapeutic proteins.

  17. Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries

    Directory of Open Access Journals (Sweden)

    Jain PP


    Full Text Available Pritesh P Jain,1 Regina Leber,1,2 Chandran Nagaraj,1 Gerd Leitinger,3 Bernhard Lehofer,4 Horst Olschewski,1,5 Andrea Olschewski,1,6 Ruth Prassl,1,4 Leigh M Marsh11Ludwig Boltzmann Institute for Lung Vascular Research, 2Biophysics Division, Institute of Molecular Biosciences, University of Graz, 3Research Unit Electron Microscopic Techniques, Institute of Cell Biology, Histology, and Embryology, 4Institute of Biophysics, 5Division of Pulmonology, Department of Internal Medicine, 6Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, AustriaAbstract: Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl-3-trimethylammonium-propane (DOTAP in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited

  18. Theranostic liposomes for cancer diagnosis and treatment: current development and pre-clinical success. (United States)

    Muthu, Madaswamy S; Feng, Si-Shen


    Liposomes are one of the effective drug delivery systems that are developed based on the nanotechnology concept. Liposomal formulation is the first nanomedicine approved by the US FDA for clinical application. Recently, the marketed liposomes and stealth liposomes have made impact for cancer therapy. In addition, a few receptor-targeted liposome products have been in different phases of clinical trials, which are yet to be marketed. In the present editorial, the advantages of vitamin E TPGS-coated liposomes over the currently available PEG-coated liposomes will be described and their great potentials for nanotheranostics for cancer imaging and therapy will be covered.

  19. Delivery of aerosolized drugs encapsulated in liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Yung-Sung; Lyons, C.R. [Univ. of New Mexico, Albuquerque, NM (United States); Schmid, M.H.


    Mycobacterium tuberculosis (Mtb) is an infectious disease that resides in the human lung. Due to the difficulty in completely killing off the disease in infected individuals, Mtb has developed drug-resistant forms and is on the rise in the human population. Therefore, ITRI and the University of New Mexico are collaborating to explore the treatment of Mtb by an aerosolized drug delivered directly to the lungs. In conclusion, it is feasible to obtain an appropriate size and concentration of the liposomes before and after aerosolization.

  20. Analysis of individual lipoproteins and liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Robbins, D.L.; Keller, R.A.; Nolan, J.P. [and others


    We describe the application of single molecule detection (SMD) technologies for the analysis of natural (serum lipoproteins) and synthetic (liposomes) transport systems. The need for advanced analytical procedures of these complex and important systems is presented with the specific enhancements afforded by SMD with flowing sample streams. In contrast to bulk measurements which yield only average values, measurement of individual species allows creation of population histograms from heterogeneous samples. The data are acquired in minutes and the analysis requires relatively small sample quantities. Preliminary data are presented from the analysis of low density lipoprotein, and multilamellar and unilamellar vesicles.

  1. Silica-Coated Liposomes for Insulin Delivery

    Directory of Open Access Journals (Sweden)

    Neelam Dwivedi


    Full Text Available Liposomes coated with silica were explored as protein delivery vehicles for their enhanced stability and improved encapsulation efficiency. Insulin was encapsulated within the fluidic phosphatidylcholine lipid vesicles by thin film hydration at pH 2.5, and layer of silica was formed above lipid bilayer by acid catalysis. The presence of silica coating and encapsulated insulin was identified using confocal and electron microscopy. The native state of insulin present in the formulation was evident from Confocal Micro-Raman spectroscopy. Silica coat enhances the stability of insulin-loaded delivery vehicles. In vivo study shows that these silica coated formulations were biologically active in reducing glucose levels.

  2. In vitro and in vivo aspects of N-acyl-phosphatidylethanolamine-containing liposomes

    DEFF Research Database (Denmark)

    Vermehren, C.; Clausen-Beck, B.; Frøkjær, S.


    Incorporation of the phospholipid, N-acyl-phosphatidylethanolamine (NAPE), has shown to increase the liposomal stability towards plasma components in vitro. Besides increasing the circulation-time, NAPE has been shown to contain fusiogenic properties. Hence, fusion between NAPE-liposomes and target...... cells may be expected, resulting in a favorable delivery of drug to the target cell. In this study, NAPE has been tested as a potential liposomal component of phosphatidylcholine-liposomes. The liposomes were characterized by size, long-term stability and phase transition temperature (T). In vivo...... behavior of NAPE-liposomes was determined by the blood-circulation half-life in mice. A characterization of the liposomes revealed that high content of NAPE resulted in liposomes of increased size compared to pure phosphatidylcholine-liposomes. However, the liposomes showed only a slight increase in size...

  3. Binding and interstitial penetration of liposomes within avascular tumor spheroids. (United States)

    Kostarelos, Kostas; Emfietzoglou, Dimitris; Papakostas, Alexandros; Yang, Wei-Hong; Ballangrud, Ase; Sgouros, George


    The liposomal delivery of cancer therapeutics, including gene therapy vectors, is an area of intense study. Poor penetration of liposomes into interstitial tumor spaces remains a problem, however. In this work, the penetration of different liposomal formulations into prostate carcinoma spheroids was examined. Spheroid penetration was assessed by confocal microscopy of fluorescently labeled liposomes. The impact of liposomal surface charge, mean diameter, lipid bilayer fluidity and fusogenicity on spheroid penetration was examined. A variety of different liposome systems relevant to clinical or preclinical protocols have been studied, including classical zwitterionic (DMPC:chol) and sterically stabilized liposomes (DMPC:chol:DOPE-PEG2000), both used clinically, and cationic liposomes (DMPC:DOPE:DC-chol and DOTAP), forming the basis of the vast majority of nonviral gene transfer vectors tested in various cancer trials. Surface interactions between strongly cationic vesicles and the tumor cells led to an electrostatically derived binding-site barrier effect, inhibiting further association of the delivery systems with the tumor spheroids (DMPC:DC-chol). However, inclusion of the fusogenic lipid DOPE and use of a cationic lipid of lower surface charge density (DOTAP instead of DC-chol) led to improvements in the observed intratumoral distribution characteristics. Sterically stabilized liposomes did not interact with the tumor spheroids, whereas small unilamellar classical liposomes exhibit extensive distribution deeper into the tumor volume. Engineering liposomal delivery systems with a relatively low charge molar ratio and enhanced fusogenicity, or electrostatically neutral liposomes with fluid bilayers, offered enhanced intratumoral penetration. This study shows that a delicate balance exists between the strong affinity of delivery systems for the tumor cells and the efficient penetration and distribution within the tumor mass, similar to previous work studying

  4. Effect of Lipid Composition on In Vitro Release and Skin Deposition of Curcumin Encapsulated Liposomes

    Directory of Open Access Journals (Sweden)

    Geethi Pamunuwa


    Full Text Available Liposomal encapsulation improves numerous physiochemical and biological properties of curcumin. The aim of this work was to impart slow release and skin delivery of curcumin via liposomal encapsulation. Liposomes were made using egg yolk phosphatidylcholine as the staple lipid while incorporating polysorbate 80 and stearylamine to prepare hybrid liposomes and positively charged liposomes, respectively. Negatively charged liposomes exhibited the highest encapsulation efficiencies (87.8±4.3% and loading capacities (3.4±0.2%. The sizes of all formulations were about 250 nm, while stearylamine increased the polydispersity index. Positively charged liposomes showed lower degradation temperatures than negatively charged liposomes by 10–15°C, attributable to the presence of stearylamine. The melting temperatures of positively charged liposomes (40–50°C were much higher than those of negatively charged liposomes (14-15°C, which may have affected release and skin deposition behavior of liposomes. The positively charged liposomes exhibited the slowest release of curcumin in phosphate buffered saline (pH 6.8 and the release profiles of all liposomal formulations conformed to the Gompertz model. The negatively charged liposomes facilitated the highest skin deposition of curcumin as revealed by studies conducted using excised pig ear skin. Concisely, positively and negatively charged liposomes were optimal for slow release and skin deposition of curcumin, respectively.

  5. Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Lipinski, Michael J., E-mail: [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Albelda, M. Teresa [GIBI2" 3" 0, Grupo de Investigación Biomédica en Imagen, IIS La Fe, Valencia (Spain); Frias, Juan C. [Departamento de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, Valencia (Spain); Anderson, Stasia A. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Arai, Andrew E. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Epstein, Stephen E. [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States)


    Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia–reperfusion murine myocardial infarction model. Methods: Mice underwent ischemia–reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24 h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. Results: The mean size of the liposomes was 100 nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163 ± 31% vs. 13 ± 14%, p = 0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

  6. Development of liposomal salbutamol sulfate dry powder inhaler formulation. (United States)

    Huang, Wen-Hua; Yang, Zhi-Jun; Wu, Heng; Wong, Yuen-Fan; Zhao, Zhong-Zhen; Liu, Liang


    The purpose of our study was to develop a formulation of liposomal salbutamol sulfate (SBS) dry powder inhaler (DPI) for the treatment of asthma. Liposomes of high encapsulation efficiency (more than 80%) were prepared by a vesicular phospholipid gel (VPG) technique. SBS VPG liposomes were subjected to lyophilization using different kinds of cryoprotectants in various mass ratios. Coarse lactose (63-106 microm) in different mass ratios was used as a carrier. Magnesium stearate (0.5%) was added as a lubricator. The dry liposomal powders were then crushed by ball milling and sieved through a 400-mesh sieve to control the mean particle size at about 10 microm. The effects of different kinds of cryoprotectants and the amount of lactose carrier on the fine particle fraction (FPF) of SBS were investigated. The results showed that the developed formulation of liposomal dry powder inhaler was obtained using lactose as a cryoprotectant with a mass ratio of lyophilized powder to carrier lactose at 1 : 5; 0.5% magnesium stearate was used as a lubricator. The value of FPF for SBS was 41.51+/-2.22% for this formulation. Sustained release of SBS from the VPG liposomes was found in the in vitro release study. The study results offer the promising possibility of localized pulmonary liposomal SBS delivery in the anhydrous state.

  7. Liposomal cytarabine for leukemic and lymphomatous meningitis: recent developments. (United States)

    Benesch, Martin; Urban, Christian


    Liposomal cytarabine (Depocyte) is a sustained-release formulation of cytarabine developed for intrathecal administration, ensuring prolonged cytotoxic drug concentrations of cytarabine in cerebrospinal fluid. Although liposomal cytarabine is increasingly used for the treatment (and prophylaxis) of CNS involvement in patients with leukemia/lymphoma, many of the recently presented clinical trials on liposomal cytarabine were retrospective in nature or used this drug on a compassionate basis. So far, one randomized Phase III study has shown significantly better response rates in patients with lymphomatous meningitis who received liposomal cytarabine compared with free cytarabine. Considerable concerns about the safety of this drug arose from recent observations that liposomal cytarabine might contribute to neurologic side effects when given too closely to high-dose systemic chemotherapy known to penetrate the brain-blood barrier. Superior efficacy of liposomal cytarabine compared with standard intrathecal therapy should be confirmed in prospective clinical trials. Careful adherence with preventive measures might help physicians to minimize side effects possibly related to the administration of liposomal cytarabine.

  8. Nanoencapsulation of quercetin and resveratrol into elastic liposomes. (United States)

    Cadena, Pabyton G; Pereira, Marcela A; Cordeiro, Rafaela B S; Cavalcanti, Isabella M F; Barros Neto, Benício; Pimentel, Maria do Carmo C B; Lima Filho, José Luiz; Silva, Valdinete L; Santos-Magalhães, Nereide S


    Based on the fact that quercetin (QUE) and resveratrol (RES) induce a synergic inhibition of the adipogenesis and increase apoptosis in adipocytes, and that sodium deoxycholate (SDC) has necrotic effects, the nanoencapsulation of QUE and RES into SDC-elastic liposomes is proposed as a new approach for dissolving the subcutaneous fat. The concentration of constituents and the effect of the drug incorporation into cyclodextrin inclusion complexes on the stability of QUE/RES-loaded liposomes were studied. The best liposomal formulation reduced the use of phosphatidylcholine and cholesterol in 17.7% and 68.4%, respectively. Liposomes presented a mean diameter of 149nm with a polydispersion index of 0.3. The zeta potential of liposomes was slightly negative (-13.3mV) due to the presence of SDC in the phospholipid bilayer. Encapsulation efficiency of QUE and RES into liposomes was almost 97%. To summarize, QUE/RES-loaded elastic liposomes are stable and suitable for subcutaneous injection, thereby providing a new strategy for reducing subcutaneous fat.

  9. Liposomes, a promising strategy for clinical application of platinum derivatives. (United States)

    Zalba, Sara; Garrido, María J


    Liposomes represent a versatile system for drug delivery in various pathologies. Platinum derivatives have been demonstrated to have therapeutic efficacy against several solid tumors. But their use is limited due to their side effects. Since liposomal formulations are known to reduce the toxicity of some conventional chemotherapeutic drugs, the encapsulation of platinum derivatives in these systems may be useful in reducing toxicity and maintaining an adequate therapeutic response. This review describes the strategies applied to platinum derivatives in order to improve their therapeutic activity, while reducing the incidence of side effects. It also reviews the results found in the literature for the different platinum-drugs liposomal formulations and their current status. The design of liposomes to achieve effectiveness in antitumor treatment is a goal for platinum derivatives. Liposomes can change the pharmacokinetic parameters of these encapsulated drugs, reducing their side effects. However, few liposomal formulations have demonstrated a significant advantage in therapeutic terms. Lipoplatin, a cisplatin formulation in Phase III, combines a reduction in the toxicity associated with an antitumor activity similar to the free drug. Thermosensitive or targeted liposomes for tumor therapy are also included in this review. Few articles about this strategy applied to platinum drugs can be found in the literature.

  10. Modulation of the carotenoid bioaccessibility through liposomal encapsulation. (United States)

    Tan, Chen; Zhang, Yating; Abbas, Shabbar; Feng, Biao; Zhang, Xiaoming; Xia, Shuqin


    The low bioaccessibility of carotenoids is currently a challenge to their incorporation in pharmaceutics, nutraceuticals and functional foods. The aim of this study was to evaluate the modulating effects of liposome encapsulation on the bioaccessibility, and its relationship with carotenoid structure and incorporated concentration. The physical stability of liposomes, lipid digestibility, carotenoids release and bioaccessibility were investigated during incubation in a simulated gastrointestinal tract. Analysis on the liposome size and morphology showed that after digestion, the majority of particles maintained spherical shape with only an increase of size in liposomes loading β-carotene or lutein. However, a large proportion of heterogeneous particles were visible in the micelle phase of liposomes loading lycopene or canthaxanthin. It was also found that the release of lutein and β-carotene from liposomes was inhibited in a simulated gastric fluid, while was slow and sustained in a simulated intestinal fluid. By contrast, lycopene and canthaxanthin exhibited fast and considerable release in the gastrointestinal media. Both carotenoid bioaccessibility and micellization content decreased with the increase of incorporated concentration. Anyway, the bioaccessibility of carotenoids after encapsulated in liposomes was in the following order: lutein>β-carotene>lycopene>canthaxanthin. Bivariate correlation analysis revealed that carotenoid bioaccessibility depended strongly on the incorporating ability of carotenoids into a lipid bilayer, loading content, and nature of the system.

  11. Liposome micropatterning based on laser-induced forward transfer (United States)

    Palla-Papavlu, Alexandra; Paraico, Iurie; Shaw-Stewart, James; Dinca, Valentina; Savopol, Tudor; Kovacs, Eugenia; Lippert, Thomas; Wokaun, Alexander; Dinescu, Maria


    The numerous properties of liposomes, i.e., nontoxicity, biodegradability, and their ability to encapsulate different biological active substances in aqueous and lipid phase, make them perfect models of biomembranes. Liposomes made up of phospholipids may be used to study new applications such as cell targeting or, under specific experimental conditions, may be applied in micro and nano-sized biosensors. This study demonstrates the capability of direct laser printing of liposomes in micron-scale patterns for the realization of biosensors or drug delivery systems. The transfer experiments were carried out onto ordinary glass substrates, and optical microscopy images reveal that well-defined patterns without splashes can be obtained for a narrow range of laser transfer fluences using 193 nm irradiation and an intermediate triazene polymer. The triazene polymer with different thicknesses was used as sacrificial layer with the purpose of protecting the liposome solution from direct laser irradiation. It was found that the thickness of the sacrificial layer should exceed 150 nm to obtain clean, debris-free patterns. Moreover, the integrity of the liposomes after laser transfer was maintained as demonstrated through fluorescence microscopy. Raman spectroscopy data suggest that the chemical composition of the liposomes does not change for transfer fluences in the range of 40 to 60 mJ/cm2. Following these results, one can envision that liposome patterns obtained by LIFT can be ultimately applied for in vitro and in vivo studies.


    Directory of Open Access Journals (Sweden)

    Vardhan Harsh


    Full Text Available Transdermal drug delivery is hardly an old technology, since 1800’s and the technology is no longer just adhesive patches. Due to recent advances in technology and the ability to apply the drug to the site of action without rupturing the skin membrane, transdermal route is becoming a widely accepted route of drug administration. Recently, various strategies have been used to augment the transdermal delivery of bioactives. Mainly, they include iontophoresis, electrophoresis, sonophoresis, chemical permeation enhancers, micro needles, and vesicular system. Among these strategies elastic liposomes appear promising. Elastic liposomes possess an infrastructure consisting of hydrophobic and hydrophilic moieties together and as a result can accommodate drug molecules with wide range of solubility. It is an ultra deformable vesicle, elastic in nature which can squeeze itself through a pore which is many times smaller than its size owing to its elasticity. They can deform and pass through narrow constriction (from 5 to 10 times less than their own diameter without measurable loss. This high deformability gives better penetration of intact vesicles. This system is much more efficient at delivering a low and high molecular weight drug to the skin in terms of quantity and depth. The article speaks specifically on various phenomenon associated with the properties of these vesicles and their transport mechanisms. It also throws light on the effectiveness of conventional and deformable vesicles as drug delivery systems as well as their possible mode of action as transdermal drug carriers.

  13. Droplet-Based Production of Liposomes (United States)

    Ackley, Donald E.; Forster, Anita


    A process for making monodisperse liposomes having lipid bilayer membranes involves fewer, simpler process steps than do related prior methods. First, a microfluidic, cross junction droplet generator is used to produce vesicles comprising aqueous solution droplets contained in single layer lipid membranes. The vesicles are collected in a lipid-solvent mix that is at most partially soluble in water and is less dense than is water. A layer of water is dispensed on top of the solvent. By virtue of the difference in densities, the water sinks to the bottom and the solvent floats to the top. The vesicles, which have almost the same density as that of water, become exchanged into the water instead of floating to the top. As there are excess lipids in the solvent solution, in order for the vesicles to remain in the water, the addition of a second lipid layer to each vesicle is energetically favored. The resulting lipid bilayers present the hydrophilic ends of the lipid molecules to both the inner and outer membrane surfaces. If lipids of a second kind are dissolved in the solvent in sufficient excess before use, then asymmetric liposomes may be formed.

  14. Liposomes to target peripheral neurons and Schwann cells.

    Directory of Open Access Journals (Sweden)

    Sooyeon Lee

    Full Text Available While a wealth of literature for tissue-specific liposomes is emerging, optimal formulations to target the cells of the peripheral nervous system (PNS are lacking. In this study, we asked whether a novel formulation of phospholipid-based liposomes could be optimized for preferential uptake by microvascular endothelia, peripheral neurons and Schwann cells. Here, we report a unique formulation consisting of a phospholipid, a polymer surfactant and cholesterol that result in enhanced uptake by targeted cells. Using fluorescently labeled liposomes, we followed particle internalization and trafficking through a distinct route from dextran and escape from degradative compartments, such as lysosomes. In cultures of non-myelinating Schwann cells, liposomes associate with the lipid raft marker Cholera toxin, and their internalization is inhibited by disruption of lipid rafts or actin polymerization. In contrast, pharmacological inhibition of clathrin-mediated endocytosis does not significantly impact liposome entry. To evaluate the efficacy of liposome targeting in tissues, we utilized myelinating explant cultures of dorsal root ganglia and isolated diaphragm preparations, both of which contain peripheral neurons and myelinating Schwann cells. In these models, we detected preferential liposome uptake into neurons and glial cells in comparison to surrounding muscle tissue. Furthermore, in vivo liposome administration by intramuscular or intravenous injection confirmed that the particles were delivered to myelinated peripheral nerves. Within the CNS, we detected the liposomes in choroid epithelium, but not in myelinated white matter regions or in brain parenchyma. The described nanoparticles represent a novel neurophilic delivery vehicle for targeting small therapeutic compounds, biological molecules, or imaging reagents into peripheral neurons and Schwann cells, and provide a major advancement toward developing effective therapies for peripheral

  15. Liposome/water lipophilicity: methods, information content, and pharmaceutical applications. (United States)

    van Balen, Georgette Plemper; Martinet, Catherine a Marca; Caron, Giulia; Bouchard, Géraldine; Reist, Marianne; Carrupt, Pierre-Alain; Fruttero, Roberta; Gasco, Alberto; Testa, Bernard


    This review discusses liposome/water lipophilicity in terms of the structure of liposomes, experimental methods, and information content. In a first part, the structural properties of the hydrophobic core and polar surface of liposomes are examined in the light of potential interactions with solute molecules. Particular emphasis is placed on the physicochemical properties of polar headgroups of lipids in liposomes. A second part is dedicated to three useful methods to study liposome/water partitioning, namely potentiometry, equilibrium dialysis, and (1)H-NMR relaxation rates. In each case, the principle and limitations of the method are discussed. The next part presents the structural information encoded in liposome/water lipophilicity, in other words the solutes' structural and physicochemical properties that determine their behavior and hence their partitioning in such systems. This presentation is based on a comparison between isotropic (i.e., solvent/water) and anisotropic (e.g., liposome/water) systems. An important factor to be considered is whether the anisotropic lipid phase is ionized or not. Three examples taken from the authors' laboratories are discussed to illustrate the factors or combinations thereof that govern liposome/water lipophilicity, namely (a) hydrophobic interactions alone, (b) hydrophobic and polar interactions, and (c) conformational effects plus hydrophobic and ionic interactions. The next part presents two studies taken from the field of QSAR to exemplify the use of liposome/water lipophilicity in structure-disposition and structure-activity relationships. In the conclusion, we summarize the interests and limitations of this technology and point to promising developments.

  16. Toxicity and immunogenicity of Neisseria meningitidis lipopolysaccharide incorporated into liposomes. (United States)

    Petrov, A B; Semenov, B F; Vartanyan, Y P; Zakirov, M M; Torchilin, V P; Trubetskoy, V S; Koshkina, N V; L'Vov, V L; Verner, I K; Lopyrev, I V


    To obtain nontoxic and highly immunogenic lipopolysaccharide (LPS) for immunization, we incorporated Neisseria meningitidis LPS into liposomes. Native LPS and its salts were incorporated by the method of dehydration-rehydration of vesicles or prolonged cosonication. The most complete incorporation of LPS into liposomes and a decrease in toxicity were achieved by the method of dehydration-rehydration of vesicles. Three forms of LPS (H+ form, Mg2+ salt, and triethanolamine salt) showed different solubilities in water, the acidic form of LPS, with the most pronounced hydrophobic properties, being capable of practically complete association with liposomal membranes. An evaluation of the activity of liposomal LPS in vitro (by the Limulus amoebocyte test) and in vivo (by monitoring the pyrogenic reaction in rabbits) revealed a decrease in endotoxin activity of up to 1,000-fold. In addition, the pyrogenic activity of liposomal LPS was comparable to that of a meningococcal polysaccharide vaccine. Liposomes had a pronounced adjuvant effect on the immune response to LPS. Thus, the level of anti-LPS plaque-forming cells in the spleens of mice immunized with liposomal LPS was 1 order of magnitude higher and could be observed for a longer time (until day 21, i.e., the term of observation) than in mice immunized with free LPS. The same regularity was revealed in a study done with an enzyme-linked immunosorbent assay. This study also established that antibodies induced by immunization belonged to the immunoglobulin M and G classes, which are capable of prolonged circulation. Moreover, liposomal LPS induced a pronounced immune response in CBA/N mice (defective in B lymphocytes of the LyB-5+ subpopulation). The latter results indicate that the immunogenic action of liposomal LPS occurs at an early age.

  17. pH-Sensitive Liposomes: Possible Clinical Implications (United States)

    Yatvin, M. B.; Kreutz, W.; Horwitz, B. A.; Shinitzky, M.


    When pH-sensitive molecules are incorporated into liposomes, drugs can be specifically released from these vesicles by a change of pH in the ambient serum. Liposomes containing the pH-sensitive lipid palmitoyl homocysteine (PHC) were constructed so that the greatest pH differential (6.0 to 7.4) of drug release was obtained near physiological temperature. Such liposomes could be useful clinically if they enable drugs to be targeted to areas of the body in which pH is less than physiological, such as primary tumors and metastases or sites of inflammation and infection.

  18. Radiolabeling of liposomes and polymeric micelles with PET-isotopes

    DEFF Research Database (Denmark)

    Jensen, Andreas Tue Ingemann

    , radiolabeled nanoparticles hold promise as a radiopharmaceutical in themselves, as a means of imaging tumor tissue, aiding in diagnosis and surgery. Chapter 2. A method for labeling liposomes with 18F (97% positron decay, T½ = 110 min) was investigated. 18F is widely available, but is hampered by a short half...... best. This substrate was radiolabeled and formulated in long‐circulating liposomes by drying the probe and the lipids together, followed by hydration by magnetic stirring. The liposomes were extruded through 100 nm filter on fully automated equipment. Animal studies were done in tumor‐bearing mice...

  19. In vivo and in vitro evaluation of octyl methoxycinnamate liposomes (United States)

    Varjão Mota, Aline de Carvalho; Faria de Freitas, Zaida Maria; Júnior, Eduardo Ricci; Dellamora-Ortiz, Gisela Maria; Santos-Oliveira, Ralph; Ozzetti, Rafael Antonio; Vergnanini, André Luiz; Ribeiro, Vanessa Lira; Silva, Ronald Santos; dos Santos, Elisabete Pereira


    Solar radiation causes damage to human skin, and photoprotection is the main way to prevent these harmful effects. The development of sunscreen formulations containing nanosystems is of great interest in the pharmaceutical and cosmetic industries because of the many potential benefits. This study aimed to develop and evaluate an octyl methoxycinnamate (OMC) liposomal nanosystem (liposome/OMC) to obtain a sunscreen formulation with improved safety and efficacy by retaining OMC for longer on the stratum corneum. Methods The liposome/OMC nanostructure obtained was tested for enzymatic hydrolysis with lipase from Rhizomucor miehei and biodistribution with liposomes labeled with technetium-99m. The liposome/OMC formulation was then incorporated in a gel formulation and tested for ocular irritation using the hen’s egg test-chorio-allantoic membrane (HET-CAM) assay, in vitro and in vivo sun protection factor, in vitro release profile, skin biometrics, and in vivo tape stripping. Results The liposome/OMC nanosystem was not hydrolyzed from R. miehei by lipase. In the biodistribution assay, the liposome/OMC formulation labeled with technetium-99m had mainly deposited in the skin, while for OMC the main organ was the liver, showing that the liposome had higher affinity for the skin than OMC. The liposome/OMC formulation was classified as nonirritating in the HET-CAM test, indicating good histocompatibility. The formulation containing liposome/OMC had a higher in vivo solar photoprotection factor, but did not show increased water resistance. Inclusion in liposomes was able to slow down the release of OMC from the formulation, with a lower steady-state flux (3.9 ± 0.33 μg/cm2/hour) compared with the conventional formulation (6.3 ± 1.21 μg/cm2/hour). The stripping method showed increased uptake of OMC in the stratum corneum, giving an amount of 22.64 ± 7.55 μg/cm2 of OMC, which was higher than the amount found for the conventional formulation (14.57 ± 2.30 μg/cm2

  20. Targeting cancer with bugs and liposomes: ready, aim, fire. (United States)

    Cheong, Ian; Huang, Xin; Thornton, Katherine; Diaz, Luis A; Zhou, Shibin


    One of the major challenges facing cancer therapy today is achieving specificity. Current efforts to meet this challenge are focused on developing targeted therapeutics specific to the cancer cell. An alternative approach is to selectively deliver cytotoxic agents to the tumor site. With this end in mind, liposomes optimized for physical robustness have been developed and used clinically as drug delivery vehicles. Paradoxically, the effectiveness of these liposomes is hampered by the suboptimal release of bioavailable drug. This article will highlight the recent advance in using a novel lipase secreted by the tumor-colonizing anaerobic bacterium Clostridium novyi-NT to induce the targeted release of liposomal payloads within tumors.

  1. In vivo and in vitro evaluation of octyl methoxycinnamate liposomes. (United States)

    Mota, Aline de Carvalho Varjão; de Freitas, Zaida Maria Faria; Ricci Júnior, Eduardo; Dellamora-Ortiz, Gisela Maria; Santos-Oliveira, Ralph; Ozzetti, Rafael Antonio; Vergnanini, André Luiz; Ribeiro, Vanessa Lira; Silva, Ronald Santos; dos Santos, Elisabete Pereira


    Solar radiation causes damage to human skin, and photoprotection is the main way to prevent these harmful effects. The development of sunscreen formulations containing nanosystems is of great interest in the pharmaceutical and cosmetic industries because of the many potential benefits. This study aimed to develop and evaluate an octyl methoxycinnamate (OMC) liposomal nanosystem (liposome/OMC) to obtain a sunscreen formulation with improved safety and efficacy by retaining OMC for longer on the stratum corneum. The liposome/OMC nanostructure obtained was tested for enzymatic hydrolysis with lipase from Rhizomucor miehei and biodistribution with liposomes labeled with technetium-99m. The liposome/OMC formulation was then incorporated in a gel formulation and tested for ocular irritation using the hen's egg test-chorio-allantoic membrane (HET-CAM) assay, in vitro and in vivo sun protection factor, in vitro release profile, skin biometrics, and in vivo tape stripping. The liposome/OMC nanosystem was not hydrolyzed from R. miehei by lipase. In the biodistribution assay, the liposome/OMC formulation labeled with technetium-99m had mainly deposited in the skin, while for OMC the main organ was the liver, showing that the liposome had higher affinity for the skin than OMC. The liposome/OMC formulation was classified as nonirritating in the HET-CAM test, indicating good histocompatibility. The formulation containing liposome/OMC had a higher in vivo solar photoprotection factor, but did not show increased water resistance. Inclusion in liposomes was able to slow down the release of OMC from the formulation, with a lower steady-state flux (3.9 ± 0.33 μg/cm(2)/hour) compared with the conventional formulation (6.3 ± 1.21 μg/cm(2)/hour). The stripping method showed increased uptake of OMC in the stratum corneum, giving an amount of 22.64 ± 7.55 μg/cm(2) of OMC, which was higher than the amount found for the conventional formulation (14.57 ± 2.30 μg/cm(2)). These results

  2. Liposomal Drug Products: A Quality by Design Approach (United States)

    Xu, Xiaoming

    Quality by Design (QbD) principles has been applied to the development of two liposomal formulations, containing a hydrophilic small molecule therapeutic (Tenofovir) and a protein therapeutic (superoxide dismutase). The goal of the research is to provide critical information on 1) how to reduce the preparation variability in liposome formulations, and 2) how to increase drug encapsulation inside liposomes to reduce manufacturing cost. Most notably, an improved liposome preparation method was developed which increased the encapsulation efficiency of hydrophilic molecules. In particular, this method allows for very high encapsulation efficiency. For example, encapsulation efficiencies of up to 50% have been achieved, whereas previously only 20% or less have been reported. Another significant outcome from this research is a first principle mathematical model to predict the encapsulation efficiency of hydrophilic drugs in unilamellar liposomes. This mathematical model will be useful in: formulation development to rapidly achieve optimized formulations; comparison of drug encapsulation efficiencies of liposomes prepared using different methods; and assisting in the development of suitable process analytical technologies to achieve real-time monitoring and control of drug encapsulation during manufacturing. A novel two-stage reverse dialysis in vitro release testing method has also been developed for passively targeted liposomes, which uses the first stage to mimic the circulation of liposomes in the body and the second stage to imitate the drug release process at the target. The developed in vitro release testing method can be used to distinguish formulations with varied compositions for quality control testing purposes. This developed method may pave the way to the development of more biorelevant quality control testing methods for liposomal drug products in the future. The QbD case studies performed in this research are examples of how this approach can be used to

  3. Novel amphiphilic probes for [18F]-radiolabeling preformed liposomes and determination of liposomal trafficking by positron emission tomography. (United States)

    Urakami, Takeo; Akai, Shuji; Katayama, Yurie; Harada, Norihiro; Tsukada, Hideo; Oku, Naoto


    Positron-emission tomography (PET) is a noninvasive real-time functional imaging system and is expected to be useful for the development of new drug candidates in clinical trials. For its application with preformulated liposomes, we devised an optimized [18F]-compound and developed a direct liposome modification method that we termed the "solid-phase transition method". We were successful in using 1-[18F]fluoro-3,6-dioxatetracosane ([18F]7a) for in vivo trafficking of liposomes. This method might be a useful tool in preclinical and clinical studies of lipidic particle-related drugs.

  4. Liposomes for targeting hepatocellular carcinoma: use of conjugated arabinogalactan as targeting ligand. (United States)

    Shah, Sanket M; Goel, Peeyush N; Jain, Ankitkumar S; Pathak, Pankaj O; Padhye, Sameer G; Govindarajan, Srinath; Ghosh, Sandipto S; Chaudhari, Pradip R; Gude, Rajiv P; Gopal, Vijaya; Nagarsenker, Mangal S


    Present study investigates the potential of chemically modified (Shah et al., 2013) palmitoylated arabinogalactan (PAG) in guiding liposomal delivery system and targeting asialoglycoprotein receptors (ASGPR) which are expressed in hepatocellular carcinoma (HCC). PAG was incorporated in liposomes during preparation and doxorubicin hydrochloride was actively loaded in preformed liposomes with and without PAG. The liposomal systems with or without PAG were evaluated for in vitro release, in vitro cytotoxicity, in vitro cell uptake on ASGPR(+) cells, in vivo pharmacokinetic study, in vivo biodistribution study, and in vivo efficacy study in immunocompromised mice. The particle size for all the liposomal systems was below 200 nm with a negative zeta potential. Doxorubicin loaded PAG liposomes released significantly higher amount of doxorubicin at pH 5.5 as compared to pH 7.4, providing advantage for targeted tumor therapy. Doxorubicin in PAG liposomes showed superior cytotoxicity on ASGPR(+) HepG2 cells as compared to ASGPR(-), MCF7, A549, and HT29 cells. Superior uptake of doxorubicin loaded PAG liposomes as compared to doxorubicin loaded conventional liposomes was evident in confocal microscopy studies. Higher AUC in pharmacokinetic study and higher deposition in liver was observed for PAG liposomes compared to conventional liposomes. Significantly higher tumor suppression was noted in immunocompromised mice for mice treated with PAG liposomes as compared to the conventional liposomes. Targeting ability and superior activity of PAG liposomes is established pre-clinically suggesting potential of targeted delivery system for improved treatment of HCC.

  5. Sustained distribution of aerosolized PEGylated liposomes in epithelial lining fluids on alveolar surfaces. (United States)

    Kaneko, Keita; Togami, Kohei; Yamamoto, Eri; Wang, Shujun; Morimoto, Kazuhiro; Itagaki, Shirou; Chono, Sumio


    The distribution characteristics of aerosolized PEGylated liposomes in alveolar epithelial lining fluid (ELF) were examined in rats, and the ensuing mechanisms were investigated in the in vitro uptake and protein adsorption experiments. Nonmodified or PEGylated liposomes (particle size 100 nm) were aerosolized into rat lungs. PEGylated liposomes were distributed more sustainably in ELFs than nonmodified liposomes. Furthermore, the uptake of PEGylated liposomes by alveolar macrophages (AMs) was less than that of nonmodified liposomes. In further in vitro uptake experiments, nonmodified and PEGylated liposomes were opsonized with rat ELF components and then added to NR8383 cells as cultured rat AMs. The uptake of opsonized PEGylated liposomes by NR8383 cells was lower than that of opsonized nonmodified liposomes. Moreover, the protein absorption levels in opsonized PEGylated liposomes were lower than those in opsonized nonmodified liposomes. These findings suggest that sustained distributions of aerosolized PEGylated liposomes in ELFs reflect evasion of liposomal opsonization with surfactant proteins and consequent reductions in uptake by AMs. These data indicate the potential of PEGylated liposomes as aerosol-based drug delivery system that target ELF for the treatment of respiratory diseases.

  6. Placing and shaping liposomes with reconfigurable DNA nanocages (United States)

    Zhang, Zhao; Yang, Yang; Pincet, Frederic; C. Llaguno, Marc; Lin, Chenxiang


    The diverse structure and regulated deformation of lipid bilayer membranes are among a cell's most fascinating features. Artificial membrane-bound vesicles, known as liposomes, are versatile tools for modelling biological membranes and delivering foreign objects to cells. To fully mimic the complexity of cell membranes and optimize the efficiency of delivery vesicles, controlling liposome shape (both statically and dynamically) is of utmost importance. Here we report the assembly, arrangement and remodelling of liposomes with designer geometry: all of which are exquisitely controlled by a set of modular, reconfigurable DNA nanocages. Tubular and toroid shapes, among others, are transcribed from DNA cages to liposomes with high fidelity, giving rise to membrane curvatures present in cells yet previously difficult to construct in vitro. Moreover, the conformational changes of DNA cages drive membrane fusion and bending with predictable outcomes, opening up opportunities for the systematic study of membrane mechanics.

  7. Potential utility of liposome bupivacaine in orthopedic surgery. (United States)

    Lonner, Jess H; Scuderi, Giles R; Lieberman, Jay R


    Management of postsurgical analgesia is an important consideration in orthopedic procedures, including joint arthroplasty. Inadequate postsurgical analgesia is associated with increased hospital length of stay, delayed ambulation, and reduced exercise capacity. In this article, we review the potential contribution of a prolonged-release liposomal formulation of bupivacaine as part of a multimodal analgesic regimen after orthopedic surgery. Controlled studies across multiple surgical settings have demonstrated that, compared with placebo and bupivacaine HCl, liposome bupivacaine in a single administration provides postsurgical analgesia for up to 72 hours, delays use of rescue medication, and reduces postsurgical opioid consumption. Liposome bupivacaine has been well tolerated in clinical studies and has had a low rate of treatment-related adverse events. To date, there has been no signal of cardiac toxicity, chondrolysis, or delayed wound healing associated with liposome bupivacaine.

  8. [Development of ultrasonic cancer therapy using ultrasound sensitive liposome]. (United States)

    Suzuki, Ryo; Oda, Yusuke; Utoguchi, Naoki; Maruyama, Kazuo


    Ultrasound (US) has been utilized as a useful tool for diagnosis and therapy. US mediated drug and gene delivery is paid to attention as a non-invasive system. The combination of US and microbubbles generated microjet stream by inducing disruption of bubbles and resulted in enhancing permeability of cell membrane. This phenomenon has been utilized as driving force for drug and gene delivery. Recently, we developed ultrasound sensitive liposome [Bubble liposome (BL)] containing perfluoropropane gas. US combined with BL could effectively transfer gene in vivo compared to conventional cationic liposomes. Using this method, we succeeded to obtain a therapeutic effect in cancer gene therapy with Interleukin-12 corded plasmid DNA. Therefore, it is expected that US combined with BL might be a useful non-viral vector system. From this result, the fusion of liposomal and ultrasound technologies would be important for establishment of advanced cancer therapy.

  9. Acoustical properties of individual liposome-loaded microbubbles. (United States)

    Luan, Ying; Faez, Telli; Gelderblom, Erik; Skachkov, Ilya; Geers, Bart; Lentacker, Ine; van der Steen, Ton; Versluis, Michel; de Jong, Nico


    A comparison between phospholipid-coated microbubbles with and without liposomes attached to the microbubble surface was performed using the ultra-high-speed imaging camera (Brandaris 128). We investigated 73 liposome-loaded microbubbles (loaded microbubbles) and 41 microbubbles without liposome loading (unloaded microbubbles) with a diameter ranging from 3-10 μm at frequencies ranging from 0.6-3.8 MHz and acoustic pressures ranging from 5-100 kPa. The experimental data showed nearly the same shell elasticity for the loaded and unloaded bubbles, but the shell viscosity was higher for loaded bubbles compared with unloaded bubbles. For loaded bubbles, a higher pressure threshold for the bubble vibrations was noticed. In addition, an "expansion-only" behavior was observed for up to 69% of the investigated loaded bubbles, which mostly occurred at low acoustic pressures (≤30 kPa). Finally, fluorescence imaging showed heterogeneity of liposome distributions of the loaded bubbles.

  10. Formulation of a New Generation of Liposomes from Bacterial and ...

    African Journals Online (AJOL)

    Formulation of a New Generation of Liposomes from. Bacterial and ... Their morphological characteristics were assessed by atomic force microscopy. (AFM). Results: At ..... Moghimipour E, Kargar M, Ramezani Z, Handali S. The potent in vitro ...

  11. Remote loading of preencapsulated drugs into stealth liposomes. (United States)

    Sur, Surojit; Fries, Anja C; Kinzler, Kenneth W; Zhou, Shibin; Vogelstein, Bert


    Loading drugs into carriers such as liposomes can increase the therapeutic ratio by reducing drug concentrations in normal tissues and raising their concentrations in tumors. Although this strategy has proven advantageous in certain circumstances, many drugs are highly hydrophobic and nonionizable and cannot be loaded into liposomes through conventional means. We hypothesized that such drugs could be actively loaded into liposomes by encapsulating them into specially designed cyclodextrins. To test this hypothesis, two hydrophobic drugs that had failed phase II clinical trials because of excess toxicity at deliverable doses were evaluated. In both cases, the drugs could be remotely loaded into liposomes after their encapsulation (preloading) into cyclodextrins and administered to mice at higher doses and with greater efficacy than possible with the free drugs.

  12. Bioreactor droplets from liposome-stabilized all-aqueous emulsions (United States)

    Dewey, Daniel C.; Strulson, Christopher A.; Cacace, David N.; Bevilacqua, Philip C.; Keating, Christine D.


    Artificial bioreactors are desirable for in vitro biochemical studies and as protocells. A key challenge is maintaining a favourable internal environment while allowing substrate entry and product departure. We show that semipermeable, size-controlled bioreactors with aqueous, macromolecularly crowded interiors can be assembled by liposome stabilization of an all-aqueous emulsion. Dextran-rich aqueous droplets are dispersed in a continuous polyethylene glycol (PEG)-rich aqueous phase, with coalescence inhibited by adsorbed ~130-nm diameter liposomes. Fluorescence recovery after photobleaching and dynamic light scattering data indicate that the liposomes, which are PEGylated and negatively charged, remain intact at the interface for extended time. Inter-droplet repulsion provides electrostatic stabilization of the emulsion, with droplet coalescence prevented even for submonolayer interfacial coatings. RNA and DNA can enter and exit aqueous droplets by diffusion, with final concentrations dictated by partitioning. The capacity to serve as microscale bioreactors is established by demonstrating a ribozyme cleavage reaction within the liposome-coated droplets.

  13. Liposome surface charge influence on skin penetration behaviour. (United States)

    Gillet, A; Compère, P; Lecomte, F; Hubert, P; Ducat, E; Evrard, B; Piel, G


    Vesicular systems have shown their ability to increase dermal and transdermal drug delivery. Their mechanism of drug transport into and through the skin has been investigated but remains a much debated question. Several researchers have outlined that drug penetration can be influenced by modifying the surface charge of liposomes. In the present work we study the influence of particle surface charge on skin penetration. The final purpose is the development of a carrier system which is able to enhance the skin delivery of two model drugs, betamethasone and betamethasone dipropionate. Liposomes were characterised by their size, morphology, zeta potential, encapsulation efficiency and stability. Ex vivo diffusion studies using Franz diffusion cells were performed. Confocal microscopy was performed to visualise the penetration of fluorescently labelled liposomes into the skin. This study showed the potential of negatively charged liposomes to enhance the skin penetration of betamethasone and betamethasone dipropionate.

  14. Atmospheric-pressure guided streamers for liposomal membrane disruption (United States)

    Svarnas, P.; Matrali, S. H.; Gazeli, K.; Aleiferis, Sp.; Clément, F.; Antimisiaris, S. G.


    The potential to use liposomes (LIPs) as a cellular model in order to study interactions of cold atmospheric-pressure plasma with cells is herein investigated. Cold atmospheric-pressure plasma is formed by a dielectric-barrier discharge reactor. Large multilamellar vesicle liposomes, consisted of phosphatidylcholine and cholesterol, are prepared by the thin film hydration technique, to encapsulate a small hydrophilic dye, i.e., calcein. The plasma-induced release of calcein from liposomes is then used as a measure of liposome membrane integrity and, consequently, interaction between the cold atmospheric plasma and lipid bilayers. Physical mechanisms leading to membrane disruption are suggested, based on the plasma characterization including gas temperature calculation.

  15. Interactions between cationic liposomes and drugs or biomolecules

    Directory of Open Access Journals (Sweden)



    Full Text Available Multiple uses for synthetic cationic liposomes composed of dioctadecyldimethylammonium bromide (DODAB bilayer vesicles are presented. Drugs or biomolecules can be solubilized or incorporated in the cationic bilayers. The cationic liposomes themselves can act as antimicrobial agents causing death of bacteria and fungi at concentrations that barely affect mammalian cells in culture. Silica particles or polystyrene microspheres can be functionalized by coverage with DODAB bilayers or phospholipid monolayers. Negatively charged antigenic proteins can be carried by the cationic liposomes which generate a remarkable immunoadjuvant action. Nucleotides or DNA can be physically adsorbed to the cationic liposomes to be transferred to mammalian cells for gene therapy. An overview of the interactions between DODAB vesicles and some biomolecules or drugs clearly points out their versatility for useful applications in a near future.

  16. Interactions between cationic liposomes and drugs or biomolecules. (United States)

    Carmona-Ribeiro, A M


    Multiple uses for synthetic cationic liposomes composed of dioctadecyldimethylammonium bromide (DODAB) bilayer vesicles are presented. Drugs or biomolecules can be solubilized or incorporated in the cationic bilayers. The cationic liposomes themselves can act as antimicrobial agents causing death of bacteria and fungi at concentrations that barely affect mammalian cells in culture. Silica particles or polystyrene microspheres can be functionalized by coverage with DODAB bilayers or phospholipid monolayers. Negatively charged antigenic proteins can be carried by the cationic liposomes which generate a remarkable immunoadjuvant action. Nucleotides or DNA can be physically adsorbed to the cationic liposomes to be transferred to mammalian cells for gene therapy. An overview of the interactions between DODAB vesicles and some biomolecules or drugs clearly points out their versatility for useful applications in a near future.

  17. Atmospheric-pressure guided streamers for liposomal membrane disruption

    Energy Technology Data Exchange (ETDEWEB)

    Svarnas, P.; Aleiferis, Sp. [High Voltage Laboratory, Department of Electrical and Computer Engineering, University of Patras, Rion 26504 (Greece); Matrali, S. H. [Pharmaceutical Technology Laboratory, Department of Pharmacy, University of Patras, Rion 26504 (Greece); Gazeli, K. [High Voltage Laboratory, Department of Electrical and Computer Engineering, University of Patras, Rion 26504 (Greece); IPREM-LCABIE, Plasmas et Applications, UPPA, 64000 Pau (France); Clement, F. [IPREM-LCABIE, Plasmas et Applications, UPPA, 64000 Pau (France); Antimisiaris, S. G. [Pharmaceutical Technology Laboratory, Department of Pharmacy, University of Patras, Rion 26504 (Greece); Institute of Chemical Engineering Sciences (ICES)-FORTH, Rion 26504 (Greece)


    The potential to use liposomes (LIPs) as a cellular model in order to study interactions of cold atmospheric-pressure plasma with cells is herein investigated. Cold atmospheric-pressure plasma is formed by a dielectric-barrier discharge reactor. Large multilamellar vesicle liposomes, consisted of phosphatidylcholine and cholesterol, are prepared by the thin film hydration technique, to encapsulate a small hydrophilic dye, i.e., calcein. The plasma-induced release of calcein from liposomes is then used as a measure of liposome membrane integrity and, consequently, interaction between the cold atmospheric plasma and lipid bilayers. Physical mechanisms leading to membrane disruption are suggested, based on the plasma characterization including gas temperature calculation.

  18. Infective endocarditis - the effect of liposomes as carrier substance ...

    African Journals Online (AJOL)


    May 18, 1991 ... prolonged inuavenous feeding through cenual venous lines.4. -. 6. Rheumatic heart disease ... whether valvular damage from lE in rabbits could be reduced by the adminisuation of ... me liposome carrier system. The ai-AT ...

  19. Utilization of liposomes for studying drug transfer and uptake. (United States)

    Fahr, Alfred; Liu, Xiangli


    On entry into the body of the patient, drugs have to overcome many barriers in order to reach the target. The knowledge of the ability of drugs to cross these barriers, which mostly consist of lipid membranes, is of utmost interest in pharmacy.High values of lipophilicity of a drug might be a good pre-requisite for crossing these barriers. It also led liposomologists to think that highly lipophilic drugs may "stick" in the lipophilic interior of liposomal phospholipid membranes and therefore these liposomes may act as a retard formulation of the lipophilic drug.The presented method here estimates the transfer time of lipophilic drugs between liposomal lipid bilayers. This may help to judge the presumed retardation function of a specific liposomal delivery system for a chosen lipophilic drug.

  20. Light activated liposomes: Functionality and prospects in ocular drug delivery. (United States)

    Lajunen, Tatu; Nurmi, Riikka; Kontturi, Leena; Viitala, Lauri; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto


    Ocular drug delivery, especially to the retina and choroid, is a major challenge in drug development. Liposome technology may be useful in ophthalmology in enabling new routes of delivery, prolongation of drug action and intracellular drug delivery, but drug release from the liposomes should be controlled. For that purpose, light activation may be an approach to release drug at specified time and site in the eye. Technical advances have been made in the field of light activated drug release, particularly indocyanine green loaded liposomes are a promising approach with safe materials and effective light triggered release of small and large molecules. This review discusses the liposomal drug delivery with light activated systems in the context of ophthalmic drug delivery challenges.

  1. Interaction of isopropylthioxanthone with phospholipid liposomes. (United States)

    Momo, Federico; Fabris, Sabrina; Stevanato, Roberto


    Isopropylthioxanthone (ITX) is a highly lipophilic molecule which can be released in foods and beverages from the packages, where it is present as photoinitiator of inks in printing processes. Recently it was found in babies milk, and its toxicity cannot be excluded. The structure of the molecule suggests a possible strong interaction with the lipid moiety of biological membranes, and this is the first study of its effects on phospholipid organization, using differential scanning calorimetry (DSC) and spin labelling techniques. The data obtained with multilamellar liposomes of saturated phospholipids of different length, with and without cholesterol, point out that the molecule changes the lipid structure; in particular, in the gel state, behaving like a disordering agent it increases the mobility of the bilayer, while, in the fluid state, tends to rigidify the membrane, in a cholesterol like way. This behavior supports the hypothesis that ITX experiences a relocation process when the lipid matrix passes from the gel to the fluid state.

  2. Advanced strategies in liposomal cancer therapy

    DEFF Research Database (Denmark)

    Andresen, Thomas Lars; Jensen, Simon Skøde; Jørgensen, Kent


    , none of them have yet led to marketed drugs and are still far from achieving this goal. The most advanced and prospective technologies are probably the prodrug strategies where nontoxic drugs are carried and activated specifically in the malignant tissue by overexpressed enzymes. In the second part......Tumor specific drug delivery has become increasingly interesting in cancer therapy, as the use of chemotherapeutics is often limited due to severe side effects. Conventional drug delivery systems have shown low efficiency and a continuous search for more advanced drug delivery principles...... is therefore of great importance. In the first part of this review, we present current strategies in the drug delivery field, focusing on site-specific triggered drug release from liposomes in cancerous tissue. Currently marketed drug delivery systems lack the ability to actively release the carried drug...

  3. Technology of Liposomal Tiosens, Cifelin and Lysomustin for Industrial Purposes (United States)

    Sanarova, E. V.; Kotova, E. A.; Lantsova, A. V.


    This work is devoted to the development of national antineoplastic drug (Tiosens, Cifelin, Lysomustin) liposomal dosage form (LDF) circuit technology and their manufacturing technology. In modern oncology liposomes, which are hollow phospholipid vesicles, are used as delivery systems protected drugs from biodegradation, and healthy cells from the toxic effect of chemotherapeutic agents. The technology of their production is stretching and multistage. It is also necessary to give consideration a lot of factors that influence on the finished product quality.

  4. Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle


    The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....

  5. Phosphatidylserine liposomes can be tethered by caldesmon to actin filaments.


    Makuch, R.; Zasada, A; K. Mabuchi; Krauze, K; C. L. Wang; Dabrowska, R


    Rotary shadowing electron microscopy revealed that attachment of caldesmon to phosphatidylserine (PS) liposomes was mainly through its C-terminal end. To determine the PS-binding sites of caldesmon, we have made use of synthetic peptides covering the two C-terminal calmodulin binding sites and a recombinant fragment corresponding to the N-terminal end of the C-terminal domain that contains an amphipathic helix. Interactions of these peptides with the PS liposomes were studied by nondenaturing...

  6. Recent advances in liposomal dry powder formulations: preparation and evaluation. (United States)

    Misra, Ambikanandan; Jinturkar, Kaustubh; Patel, Deepa; Lalani, Jigar; Chougule, Mahavir


    Liposomal drug dry powder formulations have shown many promising features for pulmonary drug administration, such as selective localization of drug within the lung, controlled drug release, reduced local and systemic toxicities, propellant-free nature, patient compliance, high dose carrying capacity, stability and patent protection. Critical review of the recent developments will provide a balanced view on benefits of liposomal encapsulation while developing dry powder formulations and will help researchers to update themselves and focus their research in more relevant areas. In liposomal dry powder formulations (LDPF), drug encapsulated liposomes are homogenized, dispersed into the carrier and converted into dry powder form by using freeze drying, spray drying and spray freeze drying. Alternatively, LDPF can also be formulated by supercritical fluid technologies. On inhalation with a suitable inhalation device, drug encapsulated liposomes get rehydrated in the lung and release the drug over a period of time. The prepared LDPF are evaluated in vitro and in vivo for lung deposition behavior and drug disposition in the lung using a suitable inhaler device. The most commonly used liposomes are composed of lung surfactants and synthetic lipids. Delivery of anticancer agents for lung cancer, corticosteroids for asthma, immunosuppressants for avoiding lung transplantation rejection, antifungal drugs for lung fungal infections, antibiotics for local pulmonary infections and cystic fibrosis and opioid analgesics for pain management using liposome technology are a few examples. Many liposomal formulations have reached the stage of clinical trials for the treatment of pulmonary distress, cystic fibrosis, lung fungal infection and lung cancer. These formulations have given very promising results in both in vitro and in vivo studies. However, modifications to new therapies for respiratory diseases and systemic delivery will provide new challenges in conducting well

  7. Liposomal Amphotericin B and Leishmaniasis: Dose and Response


    Shyam Sundar; Jaya Chakravarty


    Liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). It is the treatment of choice for immunocompetent patients in the Mediterranean region and the preferred drug for HIV/VL co-infection. Although there is a regional variation in the susceptibility of the parasite a total dose of 20 mg/kg is effective in immunocompetent patients. Randomized clinical trials of liposomal amphotericin B in the treatment and secondary prophylaxis of HIV-VL coinfec...

  8. Calcium phosphate formation in aqueous suspensions of multilamellar liposomes. (United States)

    Eanes, E D; Hailer, A W; Costa, J L


    The present study examined calcium phosphate precipitation in aqueous suspensions of multilamellar liposomes as a possible in vitro model for matrix vesicle mineralization. Liposomes were prepared by dispersing CHCl3-evaporated thin films of 7:2:1 and 7:1:1 molar mixtures of phosphatidylcholine, dicetyl phosphate, and cholesterol in aqueous solutions containing 0, 25, or 50 mM PO4 and 0 or 0.8 mM Mg. After removal of unencapsulated PO4 by gel filtration, the liposomes were suspended in 1.33 mM Ca/0.8 mM Mg solutions and made permeable to these cations by the addition of the ionophore X-537A. All experiments were carried out at pH 7.4, 22 degrees C, and 240 mOsm. In the absence of entrapped PO4, Ca2+ taken up by the liposomes was largely bound to inner membrane surfaces. With PO4 present, Ca2+ uptake increased as much as sixfold with maximum accumulations well above values sufficient for solid formation. Precipitated solids appeared to be located predominantly in the aqueous intermembranous spaces of the liposomes. Amorphous calcium phosphate (ACP) precipitated initially in the presence of entrapped Mg2+, then subsequently converted to apatite intermixed with some octacalcium phosphate. The stability of the liposomal ACP was somewhat greater than that observed in bulk solutions under comparable conditions of pH, temperature, and electrolyte makeup. In time, the mineral deposits caused entrapped PO4 to leak from the liposomes. These findings suggest that the precipitation within liposomes is similar to that which occurs in macro-volume synthetic systems but that the precipitated solid eventually impairs the integrity of the surrounding intermembranous space.(ABSTRACT TRUNCATED AT 250 WORDS)


    Directory of Open Access Journals (Sweden)



    Full Text Available Purpose: Liposomal formulations have been successfully used in the treatment of a number of dermatological diseases. Various synthetic as well as herbal drugs are incorporated into liposome to improve its efficacy. Incorporation of herbal extract into liposome reduces side effects which are associated with the synthetic ones. Azadirachta indica leaves possesse good anti bacterial activity, confirming the great potential of bioactive compounds of neem. Among aqueous extract and alcoholic extract, alcoholic leaf extracts of A. indica were found to be more active towards the bacterial species. Hence, this extract was incorporated into liposomes to enhance its activity in skin delivery. The objective of the present research work is to convert this age old miraculous herb into nanotechnology based formulations i.e. liposomes. An attempt has been made to prepare liposomal Neem gel for topical use for anti-microbial activity. Methods: Methanolic Neem Extract (MeNE was incorporated into liposomes by thin film hydration method. The batch having lipid ratio i.e. Soya lecithin: Cholesterol (4:1; MeNE concentration 80 mg with entrapment efficiency 69.52 ±1.9% was finalized. Results and Conclusions: The vesicle size was found to be 3.2μm ± 0.67. In vitro drug diffusion and skin retention from liposomal gel was found to be 62.178% ± 0.91 and 20.03% ± 0.63 respectively. Stability studies indicated that formulation was stable over a period of 3 months when stored at 2-8°C.

  10. Interaction of curcumin with lipid monolayers and liposomal bilayers. (United States)

    Karewicz, Anna; Bielska, Dorota; Gzyl-Malcher, Barbara; Kepczynski, Mariusz; Lach, Radosław; Nowakowska, Maria


    Curcumin shows huge potential as an anticancer and anti-inflammatory agent. However, to achieve a satisfactory bioavailability and stability of this compound, its liposomal form is preferable. Our detailed studies on the curcumin interaction with lipid membranes are aimed to obtain better understanding of the mechanism and eventually to improve the efficiency of curcumin delivery to cells. Egg yolk phosphatidylcholine (EYPC) one-component monolayers and bilayers, as well as mixed systems containing additionally dihexadecyl phosphate (DHP) and cholesterol, were studied. Curcumin binding constant to EYPC liposomes was determined based on two different methods: UV/Vis absorption and fluorescence measurements to be 4.26×10(4)M(-1) and 3.79×10(4)M(-1), respectively. The fluorescence quenching experiment revealed that curcumin locates in the hydrophobic region of EYPC liposomal bilayer. It was shown that curcumin impacts the size and stability of the liposomal carriers significantly. Loaded into the EYPC/DPH/cholesterol liposomal bilayer curcumin stabilizes the system proportionally to its content, while the EYPC/DPH system is destabilized upon drug loading. The three-component lipid composition of the liposome seems to be the most promising system for curcumin delivery. An interaction of free and liposomal curcumin with EYPC and mixed monolayers was also studied using Langmuir balance measurements. Monolayer systems were treated as a simple model of cell membrane. Condensing effect of curcumin on EYPC and EYPC/DHP monolayers and loosening influence on EYPC/DHP/chol ones were observed. It was also demonstrated that curcumin-loaded EYPC liposomes are more stable upon interaction with the model lipid membrane than the unloaded ones.

  11. Development of a liposomal nanodelivery system for nevirapine

    Directory of Open Access Journals (Sweden)

    Krishnan Uma M


    Full Text Available Abstract Background The treatment of AIDS remains a serious challenge owing to high genetic variation of Human Immunodeficiency Virus type 1 (HIV-1. The use of different antiretroviral drugs (ARV is significantly limited by severe side-effects that further compromise the quality of life of the AIDS patient. In the present study, we have evaluated a liposome system for the delivery of nevirapine, a hydrophobic non-nucleoside reverse transcriptase inhibitor. Liposomes were prepared from egg phospholipids using thin film hydration. The parameters of the process were optimized to obtain spherical liposomes below 200 nm with a narrow polydispersity. The encapsulation efficiency of the liposomes was optimized at different ratios of egg phospholipid to cholesterol as well as drug to total lipid. The data demonstrate that encapsulation efficiency of 78.14% and 76.25% were obtained at egg phospholipid to cholesterol ratio of 9:1 and drug to lipid ratio of 1:5, respectively. We further observed that the size of the liposomes and the encapsulation efficiency of the drug increased concomitantly with the increasing ratio of drug and lipid and that maximum stability was observed at the physiological pH. Thermal analysis of the drug encapsulated liposomes indicated the formation of a homogenous drug-lipid system. The magnitude of drug release from the liposomes was examined under different experimental conditions including in phosphate buffered saline (PBS, Dulbecco's Modified Eagle's Medium (DMEM supplemented with 10% fetal bovine serum or in the presence of an external stimulus such as low frequency ultrasound. Within the first 20 minutes 40, 60 and 100% of the drug was released when placed in PBS, DMEM or when ultrasound was applied, respectively. We propose that nevirapine-loaded liposomal formulations reported here could improve targeted delivery of the anti-retroviral drugs to select compartments and cells and alleviate systemic toxic side effects as a

  12. Interaction of fluoxetine with phosphatidylcholine liposomes. (United States)

    Momo, Federico; Fabris, Sabrina; Stevanato, Roberto


    Fluoxetine (Prozac) is one of the latest of a new generation of antidepressants, approved by FDA in 2002. The interactions of fluoxetine with multilamellar liposomes of pure phosphatidylcholine (PC) or containing cholesterol 10% molar were studied as a function of the lipid chain lengths, using differential scanning calorimetry and spin labelling EPR techniques. The DSC profiles of the gel-to-fluid state transition of liposomes of DMPC (C14:0) are broadened and shifted towards lower temperatures at increasing dopant concentrations and, with less than 10% fluoxetine, any detectable transition is destroyed. The broadened profiles and the lowered transition temperatures demonstrate that both the size and the packing of the cooperative units undergoing the transition are modified by fluoxetine, leading to a looser and more flexible bilayer. No phase separation was observed. The effects of fluoxetine on the thermotropic phase behaviour of DPPC (C16:0) and, even more, of DSPC (C18:0) are different from that of DMPC. In fact, in the former cases, two peaks appeared at increasing dopant concentrations, suggesting the occurrence of a phase separation phenomenon, which is a sign of a binding of fluoxetine in the phosphate region. In cholesterol containing membranes, fluoxetine, even at low concentrations, leads to a general corruption of the membrane, both in terms of packing and cooperativity, and the formation of any new phase is no longer observable. EPR spectra reflect the disordered motion of acyl chains in the bilayer. It was found that fluoxetine lowers the order of the lipid chains mainly in correspondence of the fifth carbon position of SASL, indicating a possible accumulation near the interfacial region.

  13. Liposomal cisplatin: a new cisplatin formulation. (United States)

    Stathopoulos, George P


    Over the last three decades, cisplatin has been one of the most effective cytotoxic agents, but its administration has been hindered by its nephrotoxicity, neurotoxicity and myelo toxicity. Recently, liposomal cisplatin, lipoplatin, has been formulated and tested thoroughly in preclinical (in vitro) and phase I, II and III trials, as documented in the literature. Experiments in animals showed that lipoplatin is less toxic than cisplatin and that it produces tumour reduction. The histological examination of treated tumours from mouse xenografts was consistent with apoptosis in the tumour cells in a mechanism similar to that of cisplatin. Lipoplatin infusion in patients and measurements of platinum levels in tumour specimens showed 10-50 times higher levels in tumours and metastases than in the adjacent normal specimens. A phase I-II study using a combination of lipoplatin and gemcitabine in pretreated patients (with disease progression or stable disease) with advanced pancreatic cancer was conducted. No nephrotoxicity was observed. With lipoplatin monotherapy the dose-limiting toxicity was determined to be 350 mg/m and the maximum tolerated dose 300 mg/m; when used in combination with paclitaxel the dose-limiting toxicity for lipoplatin was 250 mg/m and for paclitaxel 175 mg/m, and the maximum tolerated dose was 200 and 175 mg/m, respectively. In two phase II randomized studies comparing the lipoplatin combination versus the cisplatin combination, it was found that the former was statistically significantly less toxic than the latter, whereas the response rate and survival were similar. Up to now, the data on lipoplatin treatment in malignant tumours are quite impressive, because of the negligible toxicity and because it is equal if not superior to cisplatin with regard to response rate. This review aims to chronologically document publications relevant to liposomal cisplatin to date.

  14. The antimicrobial activity of liposomal lauric acids against Propionibacterium acnes. (United States)

    Yang, Darren; Pornpattananangkul, Dissaya; Nakatsuji, Teruaki; Chan, Michael; Carson, Dennis; Huang, Chun-Ming; Zhang, Liangfang


    This study evaluated the antimicrobial activity of lauric acid (LA) and its liposomal derivatives against Propionibacterium acnes (P. acnes), the bacterium that promotes inflammatory acne. First, the antimicrobial study of three free fatty acids (lauric acid, palmitic acid and oleic acid) demonstrated that LA gives the strongest bactericidal activity against P. acnes. However, a setback of using LA as a potential treatment for inflammatory acne is its poor water solubility. Then the LA was incorporated into a liposome formulation to aid its delivery to P. acnes. It was demonstrated that the antimicrobial activity of LA was not only well maintained in its liposomal derivatives but also enhanced at low LA concentration. In addition, the antimicrobial activity of LA-loaded liposomes (LipoLA) mainly depended on the LA loading concentration per single liposomes. Further study found that the LipoLA could fuse with the membranes of P. acnes and release the carried LA directly into the bacterial membranes, thereby killing the bacteria effectively. Since LA is a natural compound that is the main acid in coconut oil and also resides in human breast milk and liposomes have been successfully and widely applied as a drug delivery vehicle in the clinic, the LipoLA developed in this work holds great potential of becoming an innate, safe and effective therapeutic medication for acne vulgaris and other P. acnes associated diseases.

  15. The Role of Liposomal Bupivacaine in Value-Based Care. (United States)

    Iorio, Richard

    Multimodal pain control strategies are crucial in reducing opioid use and delivering effective pain management to facilitate improved surgical outcomes. The utility of liposomal bupivacaine in enabling effective pain control in multimodal strategies has been demonstrated in several studies, but others have found the value of liposomal bupivacaine in such approaches to be insignificant. At New York University Langone Medical Center, liposomal bupivacaine injection and femoral nerve block were compared in their delivery of efficacious and cost-effective multimodal analgesia among patients undergoing total joint arthroplasty (TJA). Retrospective analysis revealed that including liposomal bupivacaine in a multimodal pain control protocol for TJA resulted in improved quality and efficiency metrics, decreased narcotic use, and faster mobilization, all relative to femoral nerve block, and without a significant increase in admission costs. In addition, liposomal bupivacaine use was associated with elimination of the need for patient-controlled analgesia in TJA. Thus, at Langone Medical Center, the introduction of liposomal bupivacaine to TJA has been instrumental in achieving adequate pain control, delivering high-level quality of care, and controlling costs.

  16. Folate receptor targeted liposomes encapsulating anti-cancer drugs. (United States)

    Chaudhury, Anumita; Das, Surajit


    Among all available lipid based nanoparticulate systems, the success of liposomal drug delivery system is evident by the number of liposomal products available in the market or under advanced stages of preclinical and clinical trials. Liposome has the ability to deliver chemotherapeutic agents to the targeted tissues or even inside the cancerous cells by enhanced intracellular penetration or improved tumour targeting. In the last decade, folate receptor mediated tumour targeting has emerged as an attractive alternative method of active targeting of cancer cells through liposomes due to its numerous advantages over other targeting methods. Folate receptors, also known as folate binding proteins, allow the binding and internalization of folate or folic acid into the cells by a method called folate receptor mediated endocytosis. They have restricted presence in normal cells and are mostly expressed during malignant transformation. In this review article, folate receptor targeting capability of liposomes has been described. This review article has focussed on the different cancer drugs which have been encapsulated in folate receptor targeted liposomes and their in vitro as well as in vivo efficacies in several tumour models.

  17. Interaction of dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin (United States)

    Mady, Mohsen M.; Elshemey, Wael M.


    Insulin, a peptide that has been used for decades in the treatment of diabetes, has well-defined properties and delivery requirements. Liposomes, which are lipid bilayer vesicles, have gained increasing attention as drug carriers which reduce the toxicity and increase the pharmacological activity of various drugs. The molecular interaction between (uncharged lipid) dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin has been characterized by using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction. The characteristic protein absorption band peaks, Amide I (at about 1660 cm-1) and Amide II band (at about 1546 cm-1) are potentially reduced in the liposome insulin complex. Wide-angle x-ray scattering measurements showed that the association of insulin with DPPC lipid of liposomes still maintains the characteristic DPPC diffraction peaks with almost no change in relative intensities or change in peak positions. The absence of any shift in protein peak positions after insulin being associated with DPPC liposomes indicates that insulin is successfully forming complex with DPPC liposomes with possibly no pronounced alterations in the structure of insulin molecule.

  18. Tablets of pre-liposomes govern in situ formation of liposomes: concept and potential of the novel drug delivery system. (United States)

    Vanić, Željka; Planinšek, Odon; Škalko-Basnet, Nataša; Tho, Ingunn


    The purpose of this study was to develop a novel drug delivery system for challenging drugs with potential for scale-up manufacturing and controlled release of incorporated drug. Pre-liposomes powder containing metronidazole, lecithin and mannitol, prepared by spray-drying, was mixed with different tableting excipients (microcrystalline cellulose, lactose monohydrate, mannitol, dibasic calcium phosphate, pregelatinized starch, pectin or chitosan) and compressed into tablets. The delivery system was characterized with respect to (i) dry powder characteristics, (ii) mechanical tablet properties and drug release, and (iii) liposomal characteristics. The pre-liposomes powder was free-flowing, and tablets of similarly high qualities as tablets made of physical mixtures were prepared with all excipients. Liposomes were formed in situ upon tablet disintegration, dissolution or erosion depending on the type of tablet excipient used. The liposomal characteristics and drug release were found to depend on the tablet excipient. The new delivery system offers a unique synergy between the ability of liposomes to encapsulate and protect drugs and increased stability provided by compressed formulations. It can be adjusted for drug administration via various routes, e.g. oral, buccal and vaginal.

  19. Liposome Delivery Systems for Inhalation: A Critical Review Highlighting Formulation Issues and Anticancer Applications. (United States)

    Rudokas, Mindaugas; Najlah, Mohammad; Alhnan, Mohamed Albed; Elhissi, Abdelbary


    This is a critical review on research conducted in the field of pulmonary delivery of liposomes. Issues relating to the mechanism of nebulisation and liposome composition were appraised and correlated with literature reports of liposome formulations used in clinical trials to understand the role of liposome size and composition on therapeutic outcome. A major highlight was liposome inhalation for the treatment of lung cancers. Many in vivo studies that explored the potential of liposomes as anticancer carrier systems were evaluated, including animal studies and clinical trials. Liposomes can entrap anticancer drugs and localise their action in the lung following pulmonary delivery. The safety of inhaled liposomes incorporating anticancer drugs depends on the anticancer agent used and the amount of drug delivered to the target cancer in the lung. The difficulty of efficient targeting of liposomal anticancer aerosols to the cancerous tissues within the lung may result in low doses reaching the target site. Overall, following the success of liposomes as inhalable carriers in the treatment of lung infections, it is expected that more focus from research and development will be given to designing inhalable liposome carriers for the treatment of other lung diseases, including pulmonary cancers. The successful development of anticancer liposomes for inhalation may depend on the future development of effective aerosolisation devices and better targeted liposomes to maximise the benefit of therapy and reduce the potential for local and systemic adverse effects.

  20. The combined effect of encapsulating curcumin and C6 ceramide in liposomal nanoparticles against osteosarcoma. (United States)

    Dhule, Santosh S; Penfornis, Patrice; He, Jibao; Harris, Michael R; Terry, Treniece; John, Vijay; Pochampally, Radhika


    This study examines the antitumor potential of curcumin and C6 ceramide (C6) against osteosarcoma (OS) cell lines when both are encapsulated in the bilayer of liposomal nanoparticles. Three liposomal formulations were prepared: curcumin liposomes, C6 liposomes and C6-curcumin liposomes. Curcumin in combination with C6 showed 1.5 times enhanced cytotoxic effect in the case of MG-63 and KHOS OS cell lines, in comparison with curcumin liposomes alone. Importantly, C6-curcumin liposomes were found to be less toxic on untransformed primary human cells (human mesenchymal stem cells) in comparison to OS cell lines. In addition, cell cycle assays on a KHOS cell line after treatment revealed that curcumin only liposomes induced G2/M arrest by upregulation of cyclin B1, while C6 only liposomes induced G1 arrest by downregulation of cyclin D1. C6-curcumin liposomes induced G2/M arrest and showed a combined effect in the expression levels of cyclin D1 and cyclin B1. The efficiency of the preparations was tested in vivo using a human osteosarcoma xenograft assay. Using pegylated liposomes to increase the plasma half-life and tagging with folate (FA) for targeted delivery in vivo, a significant reduction in tumor size was observed with C6-curcumin-FA liposomes. The encapsulation of two water insoluble drugs, curcumin and C6, in the lipid bilayer of liposomes enhances the cytotoxic effect and validates the potential of combined drug therapy.

  1. Antibody-Hapten Recognition at the Surface of Functionalized Liposomes Studied by SPR: Steric Hindrance of Pegylated Phospholipids in Stealth Liposomes Prepared for Targeted Radionuclide Delivery

    Directory of Open Access Journals (Sweden)

    Eliot. P. Botosoa


    Full Text Available Targeted PEGylated liposomes could increase the amount of drugs or radionuclides delivered to tumor cells. They show favorable stability and pharmacokinetics, but steric hindrance of the PEG chains can block the binding of the targeting moiety. Here, specific interactions between an antihapten antibody (clone 734, specific for the DTPA-indium complex and DTPA-indium-tagged liposomes were characterized by surface plasmon resonance (SPR. Non-PEGylated liposomes fused on CM5 chips whereas PEGylated liposomes did not. By contrast, both PEGylated and non-PEGylated liposomes attached to L1 chips without fusion. SPR binding kinetics showed that, in the absence of PEG, the antibody binds the hapten at the surface of lipid bilayers with the affinity of the soluble hapten. The incorporation of PEGylated lipids hinders antibody binding to extents depending on PEGylated lipid fraction and PEG molecular weight. SPR on immobilized liposomes thus appears as a useful technique to optimize formulations of liposomes for targeted therapy.

  2. From conventional to stealth liposomes: a new frontier in cancer chemotherapy. (United States)

    Cattel, Luigi; Ceruti, Maurizio; Dosio, Franco


    Many attempts have been made to achieve good selectivity to targeted tumor cells by preparing specialized carrier agents that are therapeutically profitable for anticancer therapy. Among these, liposomes are the most studied colloidal particles thus far applied in medicine and in particular in antitumor therapy. Although they were first described in the 1960s, only at the beginning of 1990s did the first therapeutic liposomes appear on the market. The first-generation liposomes (conventional liposomes) comprised a liposome-containing amphotericin B, Ambisome (Nexstar, Boulder, CO, USA), used as an antifungal drug, and Myocet (Elan Pharma Int, Princeton, NJ, USA), a doxorubicin-containing liposome, used in clinical trials to treat metastatic breast cancer. The second-generation liposomes ("pure lipid approach") were long-circulating liposomes, such as Daunoxome, a daunorubicin-containing liposome approved in the US and Europe to treat AIDS-related Kaposi's sarcoma. The third-generation liposomes were surface-modified liposomes with gangliosides or sialic acid, which can evade the immune system responsible for removing liposomes from circulation. The fourth-generation liposomes, pegylated liposomal doxorubicin, were called "stealth liposomes" because of their ability to evade interception by the immune system, in the same way as the stealth bomber was able to evade radar. Actually, the only stealth liposome on the market is Caelyx/Doxil (Schering-Plough, Madison NJ, USA), used to cure AIDS-related Kaposi's sarcoma, resistant ovarian cancer and metastatic breast cancer. Pegylated liposomal doxorubicin is characterized by a very long-circulation half-life, favorable pharmacokinetic behavior and specific accumulation in tumor tissues. These features account for the much lower toxicity shown by Caelyx in comparison to free doxorubicin, in terms of cardiotoxicity, vesicant effects, nausea, vomiting and alopecia. Pegylated liposomal doxorubicin also appeared to be less

  3. Tissue distribution of radiolabeled phosphatidylserine-containing liposome in mice

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    Borborema, Samanta E.T.; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Biotecnologia], e-mail:, e-mail:; Andrade Junior, Heitor F. de [Instituto de Medicina Tropical de Sao Paulo (IMTSP), Sao Paulo, SP (Brazil)], e-mail:; Osso Junior, Joao A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia], e-mail:


    Liposomes are used as drug delivery systems to modify pharmacokinetic of drugs and also to improve their action in target cells. Liposomes containing phosphatidylserine are efficiently eliminated from the blood by cells of the mononuclear phagocytic system (MPS), predominantly Kupffer cells in the liver. In this way, this is a valuable approach to treat infectious diseases involving MPS, especially leishmaniasis. Leishmaniasis is a severe parasitic disease, caused by intramacrophage protozoa Leishmania sp., and is fatal if left untreated. Leishmania resides mainly in the liver and the spleen. Antileishmanial agents containing-liposomes showed more effective therapies with reduction of toxicity and adverse side effects. The purpose of this study was to investigate the tissue distribution of radioactive meglumine antimoniate encapsulated in phosphatidylserine-containing liposome. Meglumine antimoniate was neutron irradiated inside the IEA-R1 nuclear reactor to produce antimony radiotracers, {sup 122}Sb and {sup 124}Sb, and encapsulated in liposome. Healthy mice received a single intraperitoneal dose of the radiolabeled drug. Analysis of the mean radioactive tissue concentration-time data curves showed that liver and spleen had the highest levels of radioactivity. In addition these levels of drug remained for more than 48 hours. The dominant route of elimination was via biliary excretion with slow rate. Small fraction of the drug was found in the kidneys with very fast elimination. In conclusion, the phosphatidylserine-containing liposome showed to be a very useful tool to target antileishmanial agents to MPS and to sustain the drug levels for longer times. Besides, radiolabeled liposome is the easiest approach to perform biodistribution evaluation. (author)

  4. Use of liposomal amphotericin B in bone marrow transplant.

    Directory of Open Access Journals (Sweden)

    Sastry P. S


    Full Text Available Increasing number of transplants worldwide has resulted in an increase in the incidence of fungal infections. Prolonged neutropenia, immunosuppression and graft vs. host disease all result in high predisposition to fungal infections. The likelihood of developing a fungal infection increases with the severity and duration of neutropenia, which, in the case of cancer or chemotherapy for the treatment of hematological malignancies, can range from a few days to several weeks. Invasive fungal infections are difficult to diagnose and neutropenic patients with fever often receive empirical antifungal therapy. This provides a rationale for the prophylactic use of antifungal agents. The empirical use of liposomal amphotericin B has overcome some of the difficulties usually found in this setting. The majority of clinical efficacy data related to liposomal amphotericin B are derived from compassionate use studies and case series. The major advantage of these liposomal formulations of amphotericin B is a reduction in amphotercin toxicity. Use of liposomal amphotericin has been shown to be a cost-effective approach abroad and the same has been our experience also. Commercially ambisome and Fungisome are the only products that contain true liposomes. Unlike ambisome, which needs to be used in dose of 3 mg/kg/day FungisomeTM is effective in the dose of 1-3 mg/kg bodyweight. The Indian liposomal preparation has shown to be safe and effective used in over 150 transplant patients in our experience. We conclude that the liposomal amphotericin is better-tolerated and also gives better responses in documented fungal infections.

  5. Exploring the fate of liposomes in the intestine by dynamic in vitro lipolysis

    DEFF Research Database (Denmark)

    Parmentier, Johannes; Thomas, Nicky; Müllertz, Anette


    , a dynamic in vitro lipolysis model, which so far has only been used for the in vitro characterisation of other lipid-based drug delivery systems, was applied to different liposomal formulations. Liposome size and phospholipid (PL) digestion were determined as two markers for liposome stability. In addition......Liposomes are generally well tolerated drug delivery systems with a potential use for the oral route. However, little is known about the fate of liposomes during exposure to the conditions in the gastro-intestinal tract (GIT). To gain a better understanding of liposome stability in the intestine...... of aggregates of around 1µm in diameter was observed over time. After 60min lipolysis more than 80% of PLs of the SPC-liposomes were digested, but dependent on the liposome concentration only a slight change in size and size distribution could be observed. Although EPC-3 formulations did form aggregates during...

  6. Oxidative stability of Liposomes composed of docosahexaenoic acid-containing phospholipids

    DEFF Research Database (Denmark)

    Vikbjerg, Anders Falk; Andresen, Thomas Lars; Jørgensen, Kent


    Oxidative stability of liposomes made of (Docosahexaenoic acid) DHA-containing phosphatidylcholine (PC) was examined during preparation and storage. After preparation of the liposomes, the concentration of primary (conjugated dienes) and secondary oxidation products (Thiobarbituric acid...

  7. Enhanced combination therapy effect on paclitaxel-resistant carcinoma by chloroquine co-delivery via liposomes. (United States)

    Gao, Menghua; Xu, Yuzhen; Qiu, Liyan


    A novel composite liposomal system co-encapsulating paclitaxel (PTX) with chloroquine phosphate (CQ) was designed for treating PTX-resistant carcinoma. It was confirmed that liposomal CQ can sensitize PTX by means of autophagy inhibition and competitively binding with multidrug-resistance transporters. Furthermore, according to the in vitro cytotoxicity and apoptosis assay, real-time observation of cellular uptake, and in vivo tissue distribution study, co-encapsulation of PTX and CQ in liposomes was validated as superior to the mixture of PTX liposome plus CQ liposome due to the simultaneous delivery and synergetic effect of the two drugs. Consequently, this composite liposome achieved significantly stronger anticancer efficacy in vivo than the PTX liposome plus CQ liposome mixture. This study helps to guide and enlighten ongoing and future clinical trials about the optimal administration modes for drug combination therapy.

  8. Liposomal formulations of amphotericin B: differences according to the scientific evidence. (United States)

    Azanza, José Ramón; Sádada, Belén; Reis, Joana


    This article presents an overview of the characteristics of liposomes as drug carriers, particularly in relation to liposomal formulations of amphotericin B. General features regarding structure, liposome-cell interactions, stability, encapsulation of active substances and elimination of liposomes are described. Up to the present time extensive efforts to produce similar or bioequivalent products of amphotericin B formulations, in particular in the case of liposomal amphotericin B, have been unsuccessful in spite of having a very similar composition and even an apparently identical manufacturing process. Guidelines for the development of generic liposomal formulations developed by the FDA and EMA are also summarized. Based on the available evidence of the composition of liposomes, any differences in the manufacturing process even if the same lipid composition is used may result in different final products. Therefore, it seems unreasonable to infer that all amphotericin B liposomal formulations are equal in efficacy and safety.

  9. Liposome-encapsulated aminoglycosides in pre-clinical and clinical studies

    NARCIS (Netherlands)

    R.M. Schiffelers (Raymond); G. Storm (Gert); I.A.J.M. Bakker-Woudenberg (Irma)


    textabstractLiposome-encapsulated amikacin has recently entered clinical trials. The rationale for liposome encapsulation of aminoglycosides is the possibility to increase the therapeutic index of this class of antibiotics by increasing aminoglycoside concentrations at the site of

  10. New synthetic amphiphilic polymers for steric protection of liposomes in vivo. (United States)

    Torchilin, V P; Trubetskoy, V S; Whiteman, K R; Caliceti, P; Ferruti, P; Veronese, F M


    Carboxy group-terminated synthetic polymers--branched poly(ethylene glycol), poly(acryloylmorpholine), and poly(vinylpyrrolidone)--were made amphiphilic by derivatization with phosphatidyl ethanolamine via the terminal carboxy group and then incorporated into lecithin-cholesterol liposomes prepared by the detergent dialysis method. Following the biodistribution of liposomes in mice, all three polymers were shown to be effective steric protectors for liposomes and were able to sharply increase liposome circulation times in a concentration-dependent manner. The accumulation of liposomes in the liver decreases. The effects observed are similar to those found for liposomes modified with linear poly(ethylene glycol). At low polymer concentration, amphiphilic branched poly(ethylene glycol) seems to be the most effective liposome protector, most probably, because at the same molar content of anchoring groups, each attachment point carries two polymeric chains and doubles the quantity of liposome-grafted polymer comparing to linear poly(ethylene glycol).

  11. In vivo and in vitro evaluation of octyl methoxycinnamate liposomes

    Directory of Open Access Journals (Sweden)

    de Carvalho Varjão Mota A


    Full Text Available Aline de Carvalho Varjão Mota,1 Zaida Maria Faria de Freitas,1 Eduardo Ricci Júnior,1 Gisela Maria Dellamora-Ortiz,1 Ralph Santos-Oliveira,2 Rafael Antonio Ozzetti,3 André Luiz Vergnanini,3 Vanessa Lira Ribeiro,4 Ronald Santos Silva,4 Elisabete Pereira dos Santos11Faculty of Pharmacy, Federal University of Rio de Janeiro, 2Nuclear Engineering Institute, National Nuclear Energy Commission, 3Allergisa Dermatocosmetic Research, University of Campinas, São Paulo, 4Pharmacology and Toxicology Department, National Insitute of Quality Control in Health, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilAbstract: Solar radiation causes damage to human skin, and photoprotection is the main way to prevent these harmful effects. The development of sunscreen formulations containing nanosystems is of great interest in the pharmaceutical and cosmetic industries because of the many potential benefits. This study aimed to develop and evaluate an octyl methoxycinnamate (OMC liposomal nanosystem (liposome/OMC to obtain a sunscreen formulation with improved safety and efficacy by retaining OMC for longer on the stratum corneum.Methods: The liposome/OMC nanostructure obtained was tested for enzymatic hydrolysis with lipase from Rhizomucor miehei and biodistribution with liposomes labeled with technetium-99m. The liposome/OMC formulation was then incorporated in a gel formulation and tested for ocular irritation using the hen’s egg test-chorio-allantoic membrane (HET-CAM assay, in vitro and in vivo sun protection factor, in vitro release profile, skin biometrics, and in vivo tape stripping.Results: The liposome/OMC nanosystem was not hydrolyzed from R. miehei by lipase. In the biodistribution assay, the liposome/OMC formulation labeled with technetium-99m had mainly deposited in the skin, while for OMC the main organ was the liver, showing that the liposome had higher affinity for the skin than OMC. The liposome/OMC formulation was classified as nonirritating in

  12. A stimuli responsive liposome loaded hydrogel provides flexible on-demand release of therapeutic agents

    NARCIS (Netherlands)

    O'Neill, Hugh S.; Herron, Caroline C.; Hastings, Conn L.; Deckers, Roel; Lopez Noriega, Adolfo; Kelly, Helena M.; Hennink, Wim E.; McDonnell, Ciarán O.; O'Brien, Fergal J.; Ruiz-Hernández, Eduardo; Duffy, Garry P.


    Lysolipid-based thermosensitive liposomes (LTSL) embedded in a chitosan-based thermoresponsive hydrogel matrix (denoted Lipogel) represents a novel approach for the spatiotemporal release of therapeutic agents. The entrapment of drug-loaded liposomes in an injectable hydrogel permits local liposome

  13. Poly(amino acid)s: next-generation coatings for long-circulating liposomes

    NARCIS (Netherlands)

    Romberg, B.


    Incorporation of a lipid conjugate of a water-soluble polymer into liposomes can reduce the adhesion of plasma proteins that would otherwise cause rapid recognition and removal of the liposomes by phagocytes. Such polymer-coated liposomes show prolonged circulation property and passive targeting to

  14. Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases

    NARCIS (Netherlands)

    Bartneck, M.; Scheyda, K.M.; Warzecha, K.T.; Rizzo, L.Y.; Hittatiya, K.; Luedde, T.; Storm, Gerrit; Trautwein, C.; Lammers, Twan Gerardus Gertudis Maria; Tacke, F.


    Liposomes are routinely used carrier materials for delivering drug molecules to pathological sites. Besides in tumors and inflammatory sites, liposomes also strongly accumulate in liver and spleen. The potential of using liposomes to treat acute and chronic liver disorders, however, has not yet been

  15. Poly(amino acid)s: next-generation coatings for long-circulating liposomes

    NARCIS (Netherlands)

    Romberg, B.


    Incorporation of a lipid conjugate of a water-soluble polymer into liposomes can reduce the adhesion of plasma proteins that would otherwise cause rapid recognition and removal of the liposomes by phagocytes. Such polymer-coated liposomes show prolonged circulation property and passive targeting to

  16. Massive targeting of liposomes, surface-modified with anionized albumins, to hepatic endothelial cells

    NARCIS (Netherlands)

    Kamps, J.AAM; Morselt, H.W M; Swart, P.J; Meijer, D.K F; Scherphof, Gerrit


    Human serum albumin (HSA) derivatized with cis-aconitic anhydride was covalently coupled to liposomes with a size of approximately 100 nm [polyaconitylated HSA (Aco-HSA) liposomes]. Within 30 min after injection into a rat, Aco-HSA liposomes were completely cleared from the blood and almost

  17. Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases

    NARCIS (Netherlands)

    Bartneck, Matthias; Scheyda, Katharina M; Warzecha, Klaudia T; Rizzo, Larissa Y; Hittatiya, Kanishka; Luedde, Tom; Storm, G|info:eu-repo/dai/nl/073356328; Trautwein, Christian; Lammers, Twan|info:eu-repo/dai/nl/304824577; Tacke, Frank

    Liposomes are routinely used carrier materials for delivering drug molecules to pathological sites. Besides in tumors and inflammatory sites, liposomes also strongly accumulate in liver and spleen. The potential of using liposomes to treat acute and chronic liver disorders, however, has not yet been

  18. Different intrahepatic distribution of phosphatidylglycerol and phosphatidylserine liposomes in the rat

    NARCIS (Netherlands)

    Daemen, Toos; Velinova, Maria; Regts, Djoeke; deJager, M; Kalicharan, Ruby; Donga, J; van der Want, Johannes J.L.; Scherphof, GL

    Liposomes with diameters of 200 to 400 nm containing phosphatidylserine (PS) or phosphatidylglycerol (PG) were injected intravenously into rats, Two hours after injection, T5% of the injected dose of PS liposomes was found in the liver and only 10% found in the spleen, while 35% of the PG liposomes

  19. Liposomal phosphatidylserine inhibits tumor cytotoxicity of liver macrophages induced by muramyl dipeptide and lipopolysaccharide

    NARCIS (Netherlands)

    Daemen, T; Regts, J; Scherphof, GL


    Liposomes can very efficiently deliver immunomodulators to macrophages so as to induce tumor cytotoxicity. Liposomes most widely used for that purpose contain negatively charged lipids, in particular phosphatidylserine (PS), to enhance liposome uptake by the macrophages. We investigated the effect o

  20. Cationic liposomal drug delivery system for specific targeting of human cd14+ monocytes in whole blood

    DEFF Research Database (Denmark)


    This invention concerns a liposome comprising lipids and at least one active ingredient, wherein at least one of the lipids is a cationic lipid; said liposome exhibiting a net positive charge at physiological conditions at which said liposome preferentially adheres to monocytes in freshly drawn b......, an infectious disease, an inflammatory disease, an autoimmune disease or allergy....

  1. Interaction of targeted liposomes with primary cultured hepatic stellate cells : Involvement of multiple receptor systems

    NARCIS (Netherlands)

    Adrian, Joanna Ewa; Poelstra, Klaas; Scherphof, Gerrit; Molema, Ingrid; Meijer, D.K F; Reker-Smit, Catharina; Morselt, Henriette; Kamps, Jan


    Background/Aims: In designing a versatile liposomal drug carrier to hepatic stellate cells (HSC), the interaction of mannose 6-phosphate human serum albumin (M6P-HSA) liposomes with cultured cells was studied. Methods: M6P-HSA was covalently coupled to the liposomal surface and the uptake and bindin

  2. Enhanced oral absorption of insulin-loaded liposomes containing bile salts: a mechanistic study. (United States)

    Niu, Mengmeng; Tan, Ya'nan; Guan, Peipei; Hovgaard, Lars; Lu, Yi; Qi, Jianping; Lian, Ruyue; Li, Xiaoyang; Wu, Wei


    Liposomes containing bile salts (BS-liposomes) significantly enhanced the oral bioavailability of insulin (rhINS). However, the underlying absorption mechanisms have not been well understood yet. In this study, the transiting fate of the liposomes was first investigated using fluorescent imaging tools to confirm the effect of enhanced gastrointestinal stability. In order to obtain evidence of enhanced transcellular permeation, the interaction between BS-liposomes and the biomembrane was investigated in Caco-2 cell lines. BS-liposomes were found to be more stable in the gastrointestinal tract by showing prolonged residence time in comparison with conventional liposomes. BS-liposomes were significantly more effective for cellular uptake and transport of rhINS; and this effect was found to be size- and concentration-dependent. A good linear correlation was observed between the concentration of the liposomes and uptake/transport of rhINS. Confocal laser scanning microscopy visualization further validated the transcellular transit of BS-liposomes. The BS-liposomes showed little effect on cytotoxicity and did not induce apoptosis within 24h investigation. It was concluded that BS-liposomes showed improved in vivo residence time and enhanced permeation across the biomemebranes. Mechanisms of trans-enterocytic internalization could be proposed as an interpretation for enhanced absorption of insulin-loaded liposomes.

  3. Liposomes : Vehicles for the targeted and controlled delivery of peptides and proteins

    NARCIS (Netherlands)

    Crommelin, DJA; Daemen, T; Scherphof, GL; Vingerhoeds, MH; Heeremans, JLM; Kluft, C; Storm, G


    Several approaches are presented that have been developed for the liposomal delivery of peptides and proteins. For a rational design of targeted liposomes, the anatomical and physiological constraints with respect to the distribution of liposomes in the body have to be taken into account. Target sit

  4. Curcumin liposomes prepared with milk fat globule membrane phospholipids and soybean lecithin. (United States)

    Jin, Hong-Hao; Lu, Qun; Jiang, Jian-Guo


    Using thin film ultrasonic dispersion method, the curcumin liposomes were prepared with milk fat globule membrane (MFGM) phospholipids and soybean lecithins, respectively, to compare the characteristics and stability of the 2 curcumin liposomes. The processing parameters of curcumin liposomes were investigated to evaluate their effects on the encapsulation efficiency. Curcumin liposomes were characterized in terms of size distribution, ζ-potential, and in vitro release behavior, and then their storage stability under various conditions was evaluated. The curcumin liposomes prepared with MFGM phospholipids had an encapsulation efficiency of about 74%, an average particle size of 212.3 nm, and a ζ-potential of -48.60 mV. The MFGM liposomes showed higher encapsulation efficiency, smaller particle size, higher absolute value of ζ-potential, and slower in vitro release than soybean liposomes. The retention rate of liposomal curcumin was significantly higher than that of free curcumin. The stability of the 2 liposomes under different pH was almost the same, but MFGM liposomes displayed a slightly higher stability than soybean liposomes under the conditions of Fe(3+), light, temperature, oxygen, and relative humidity. In conclusion, MFGM phospholipids have potential advantages in the manufacture of curcumin liposomes used in food systems. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Liposomal Drug Product Development and Quality: Current US Experience and Perspective. (United States)

    Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M


    Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

  6. Composition Influence on Pulmonary Delivery of Rifampicin Liposomes

    Directory of Open Access Journals (Sweden)

    Maria Letizia Manca


    Full Text Available The effects of lipid concentration and composition on the physicochemical properties, aerosol performance and in vitro toxicity activity of several rifampicin-loaded liposomes were investigated. To this purpose, six liposome formulations containing different amounts of soy phosphatidylcholine and hydrogenated soy phosphatidylcholine, with and without cholesterol and oleic acid, were prepared and fully characterized. Uni- or oligo-lamellar, small (~100 nm, negatively charged (~60 mV vesicles were obtained. Lipid composition affected aerosol delivery features of liposomal rifampicin; in particular, the highest phospholipid concentration led to a better packing of the vesicular bilayers with a consequent higher nebulization stability. The retention of drug in nebulized vesicles (NER% was higher for oleic acid containing vesicles (55% ± 1.4% than for the other samples (~47%. A549 cells were used to evaluate intracellular drug uptake and in vitro toxicity activity of rifampicin-loaded liposomes in comparison with the free drug. Cell toxicity was more evident when oleic acid containing liposomes were used.

  7. Liposomes as drug deposits in multilayered polymer films. (United States)

    Lynge, Martin E; Laursen, Marie Baekgaard; Hosta-Rigau, Leticia; Jensen, Bettina E B; Ogaki, Ryosuke; Smith, Anton A A; Zelikin, Alexander N; Städler, Brigitte


    The ex vivo growth of implantable hepatic or cardiac tissue remains a challenge and novel approaches are highly sought after. We report an approach to use liposomes embedded within multilayered films as drug deposits to deliver active cargo to adherent cells. We verify and characterize the assembly of poly(l-lysine) (PLL)/alginate, PLL/poly(l-glutamic acid), PLL/poly(methacrylic acid) (PMA), and PLL/cholesterol-modified PMA (PMAc) films, and assess the myoblast and hepatocyte adhesion to these coatings using different numbers of polyelectrolyte layers. The assembly of liposome-containing multilayered coatings is monitored by QCM-D, and the films are visualized using microscopy. The myoblast and hepatocyte adhesion to these films using PLL/PMAc or poly(styrenesulfonate) (PSS)/poly(allyl amine hydrochloride) (PAH) as capping layers is evaluated. Finally, the uptake of fluorescent lipids from the surface by these cells is demonstrated and compared. The activity of this liposome-containing coating is confirmed for both cell lines by trapping the small cytotoxic compound thiocoraline within the liposomes. It is shown that the biological response depends on the number of capping layers, and is different for the two cell lines when the compound is delivered from the surface, while it is similar when administered from solution. Taken together, we demonstrate the potential of liposomes as drug deposits in multilayered films for surface-mediated drug delivery.

  8. Formation of drug nanocrystals under nanoconfinement afforded by liposomes

    DEFF Research Database (Denmark)

    Cipolla, D.; Wu, H.; Salentinig, Stefan


    Nanocrystals of drug substances have important therapeutic applications, but their preparation is often difficult due to size control in bottom up approaches, or energetic milling and surface activation in top down processing. In this study, confinement within liposome nanocompartments is demonst......Nanocrystals of drug substances have important therapeutic applications, but their preparation is often difficult due to size control in bottom up approaches, or energetic milling and surface activation in top down processing. In this study, confinement within liposome nanocompartments......-electron tomography revealed that the majority of the liposomes contained a single drug nanocrystal, observed to physically stretch but not burst the liposomes, and the composition of the freeze-thaw medium altered the aspect ratio of the drug nanocrystals. Small angle X-ray scattering and dynamic depolarized light...... scattering were used to confirm the asymmetric nature of particles in suspension to exclude the cryoTEM preparation process as a contributor to the particle morphology. In assessing potential use in controlled release drug delivery, the in vitro release rate of ciprofloxacin from liposomes containing...

  9. Translational siRNA therapeutics using liposomal carriers: prospects & challenges. (United States)

    Bhavsar, Dhiraj; Subramanian, Krishnakumar; Sethuraman, Swaminathan; Krishnan, Uma Maheswari


    Gene silencing has emerged as a promising strategy for molecular therapy of various malignant, viral, hereditary and inflammatory disorders. However, its translation from lab to clinic is yet to gain momentum due to the numerous problems that plague its development. A multi-functional siRNA delivery system with desired properties such as enhanced immune compatibility, target specificity, high cell uptake and excellent silencing efficiency is required to understand the challenges involved in the selection and modification of small interfering RNA (siRNA), factors influencing the complexation process and the response of the biological system to the formulation. Liposomes have been used as delivery systems due to its versatility in handling different types of drugs, tunable size, charge and surface functionalities that improve its effectiveness in vivo. This review highlights the challenges involved in gene silencing and describes the progression of liposomal systems used in gene silencing. The rationale in introducing chemical modifications in siRNA, synthesizing designer cationic lipids and evolution of hybrid liposomal systems has been elaborated, emphasizing their merits and short-comings. Finally, a description of the current state of clinical trials involving liposomal formulations has been included to provide an unbiased perspective of the future of liposomal systems and gene silencing tools as therapeutic tools.

  10. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Soosay Raj TA


    Full Text Available Trisha A Soosay Raj,1 Amanda M Smith,2 Andrew S Moore,1,21Royal Children's Hospital, Children's Health Queensland Hospital and Health Service, Brisbane, Queensland, Australia; 2Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, QLD, AustraliaAbstract: Vincristine (VCR is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL, a disease that accounts for approximately one-third of all childhood cancer diagnoses. VCR's full therapeutic potential has been limited by dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory–motor neuropathy. In the last decade, however, the discovery that liposomal encapsulation of chemotherapeutics can modulate the pharmacokinetic characteristics of a compound has stimulated much interest in liposomal VCR (vincristine sulfate liposomal injection [VSLI] formulations for the treatment of ALL and other hematological malignancies. Promising data from recent clinical trials investigating VSLI in adults with ALL resulted in US Food and Drug Administration approval for use in patients with Philadelphia chromosome (t[9;22]/BCR–ABL1 (Ph-negative (Ph- disease. Additional clinical trials of VSLI in adults and children with both Ph-positive (Ph+ and Ph- ALL are ongoing. Here we review the preclinical and clinical experience to date with VSLI for ALL.Keywords: vincristine sulfate liposomal injection, liposomes, sphingosomal vincristine, acute lymphoblastic leukemia, chemotherapy

  11. Application of Liposomes in Treatment of Rheumatoid Arthritis: Quo Vadis

    Directory of Open Access Journals (Sweden)

    Bhupinder Kapoor


    Full Text Available The most common treatments for rheumatoid arthritis include nonsteroidal anti-inflammatory drugs (NSAIDs, corticosteroids, disease modifying antirheumatic drugs (DMARDs, and some biological agents. However, none of the treatments available is able to achieve the ultimate goal of treatment, that is, drug-free remission. This limitation has shifted the focus of treatment to delivery strategies with an ability to deliver the drugs into the synovial cavity in the proper dosage while mitigating side effects to other tissues. A number of approaches like microemulsions, microspheres, liposomes, microballoons, cocrystals, nanoemulsions, dendrimers, microsponges, and so forth, have been used for intrasynovial delivery of these drugs. Amongst these, liposomes have proven to be very effective for retaining the drug in the synovial cavity by virtue of their size and chemical composition. The fast clearance of intra-synovially administered drugs can be overcome by use of liposomes leading to increased uptake of drugs by the target synovial cells, which in turn reduces the exposure of nontarget sites and eliminates most of the undesirable effects associated with therapy. This review focuses on the use of liposomes in treatment of rheumatoid arthritis and summarizes data relating to the liposome formulations of various drugs. It also discusses emerging trends of this promising technology.

  12. Liposomal Encapsulation Enzymes: From Medical Applications to Kinetic Characteristics. (United States)

    Jahadi, M; Khosravi-Darani, K


    Liposomes and nanoliposomes as small vesicles composed of phospholipid bilayer (entrapping one or more hydrophilic or lipophilic components) have recently found several potential applications in medicine and food industry. These vesicles may protect the core materials from moisture, heat and other extreme conditions. They may also provide controlled release of various bioactive agents, including food ingredients at the right place and time. Potential applications of enzyme-loaded liposomes are in the medical or biomedical field, particularly for the enzymereplacement therapy, as well as cheese industry for production of functional foods with improved health beneficial impacts on the consumer. Encapsulation process has a recondite impact on enzymes. In fact, liposome preparation techniques may alter the pH and temperature optima, affinity of the enzyme to substrate (Km), and maximum rate of reaction (Vmax). In addition, in this paper, the impact of process variables on the kinetic characteristics of enzymes encapsulated in liposomes was investigated. Also, the effects of enzyme entrapment in liposomes, prepared by different methods, on the catalytic efficiency of enzyme, as well as its kinetic properties and stability compared to native (free) enzymes has been reviewed.

  13. Development and Characterization of Liposomal Doxorubicin Hydrochloride with Palm Oil

    Directory of Open Access Journals (Sweden)

    Bahareh Sabeti


    Full Text Available The usage of natural products in pharmaceuticals has steadily seen improvements over the last decade, and this study focuses on the utilization of palm oil in formulating liposomal doxorubicin (Dox. The liposomal form of Dox generally minimizes toxicity and enhances target delivery actions. Taking into account the antiproliferative and antioxidant properties of palm oil, the aim of this study is to design and characterize a new liposomal Dox by replacing phosphatidylcholine with 5% and 10% palm oil content. Liposomes were formed using the freeze_thaw method, and Dox was loaded through pH gradient technique and characterized through in vitro and ex vivo terms. Based on TEM images, large lamellar vesicles (LUV were formed, with sizes of 438 and 453 nm, having polydispersity index of 0.21 ± 0.8 and 0.22 ± 1.3 and zeta potentials of about −31 and −32 mV, respectively. In both formulations, the entrapment efficiency was about 99%, and whole Dox was released through 96 hours in PBS (pH = 7.4 at 37°C. Comparing cytotoxicity and cellular uptake of LUV with CaelyxR on MCF7 and MDA-MBA 231 breast cancer cell lines indicated suitable uptake and lower IC50 of the prepared liposomes.

  14. Development and characterization of liposomal doxorubicin hydrochloride with palm oil. (United States)

    Sabeti, Bahareh; Noordin, Mohamed Ibrahim; Mohd, Shaharuddin; Hashim, Rosnani; Dahlan, Afendi; Javar, Hamid Akbari


    The usage of natural products in pharmaceuticals has steadily seen improvements over the last decade, and this study focuses on the utilization of palm oil in formulating liposomal doxorubicin (Dox). The liposomal form of Dox generally minimizes toxicity and enhances target delivery actions. Taking into account the antiproliferative and antioxidant properties of palm oil, the aim of this study is to design and characterize a new liposomal Dox by replacing phosphatidylcholine with 5% and 10% palm oil content. Liposomes were formed using the freeze_thaw method, and Dox was loaded through pH gradient technique and characterized through in vitro and ex vivo terms. Based on TEM images, large lamellar vesicles (LUV) were formed, with sizes of 438 and 453 nm, having polydispersity index of 0.21 ± 0.8 and 0.22 ± 1.3 and zeta potentials of about -31 and -32 mV, respectively. In both formulations, the entrapment efficiency was about 99%, and whole Dox was released through 96 hours in PBS (pH = 7.4) at 37°C. Comparing cytotoxicity and cellular uptake of LUV with Caelyx(R) on MCF7 and MDA-MBA 231 breast cancer cell lines indicated suitable uptake and lower IC50 of the prepared liposomes.


    Directory of Open Access Journals (Sweden)

    M. Yasmin Begum


    Full Text Available CLX (celecoxib is a highly hydrophobic non-steroidal anti-inflammatory drug with high plasma protein binding. We describe here the encapsulation of CLX in MLVs composed of SPC and variable amounts of cholesterol. The influence of drug – lipid ratio was studied and amount of the drug could be encapsulated was optimized. The effect of cholesterol and other process parameters were studied to obtain the liposomal vesicles with desired quality. All the prepared formulations were characterized for their physico chemical properties such as appearance, vesicle size, vesicle size distribution and percentage drug entrapment. Stability of the liposomes in terms of their drug leakage and drug retention behaviour was studied by storing the liposomal formulations under different conditions for the period of 30 days. The optimized formulation parameters and process parameters resulted the liposomes with mean vesicle diameter of 4.81μ. The maximum percentage drug entrapment was achieved with the formulation CL3 which contains the drug – lipid ratio of 1:10%W/W and the percentage drug entrapment is equal to 72.33±0.64 (%. In vitro release data showed that release profile follows zero order kinetics. Celecoxib liposomes with good stability and appreciable controlled drug release with good retention of the drug even after 24 hours were prepared successfully.

  16. Assembly of liposomes controlled by triple helix formation. (United States)

    Jakobsen, Ulla; Vogel, Stefan


    Attachment of DNA to the surface of different solid nanoparticles (e.g., gold and silica nanoparticles) is well established, and a number of DNA-modified solid nanoparticle systems have been applied to thermal denaturation analysis of oligonucleotides. We report herein the noncovalent immobilization of oligonucleotides on the surface of soft nanoparticles (i.e., liposomes) and the subsequent controlled assembly by DNA triple helix formation. The noncovalent approach avoids tedious surface chemistry and necessary purification procedures and can simplify and extend the available methodology for the otherwise difficult thermal denaturation analysis of complex triple helical DNA assemblies. The approach is based on lipid modified triplex forming oligonucleotides (TFOs) which control the assembly of liposomes in solution in the presence of single- or double-stranded DNA targets. The thermal denaturation analysis is monitored by ultraviolet spectroscopy at submicromolar concentrations and compared to regular thermal denaturation assays in the absence of liposomes. We report on triplex forming oligonucleotides (TFOs) based on DNA and locked nucleic acid (LNA)/DNA hybrid building blocks and different target sequences (G or C-rich) to explore the applicability of the method for different triple helical assembly modes. We demonstrate advantages and limitations of the approach and show the reversible and reproducible formation of liposome aggregates during thermal denaturation cycles. Nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS) show independently from ultraviolet spectroscopy experiments the formation of liposome aggregates.

  17. Carriers for skin delivery of trihexyphenidyl HCl: ethosomes vs. liposomes. (United States)

    Dayan, N; Touitou, E


    The purpose of this work was to characterize a novel ethosomal carrier containing trihexyphenidyl HCl (THP) and to investigate the delivery of THP from ethosomes versus classic liposomes. THP-ethosomal systems were shown by electron microscopy to contain small, phospholipid vesicles. As the THP concentration was increased from 0 to 3%, the size of the vesicles decreased from 154 to 90 nm. This is most likely due to the surface activity of THP (critical micelle concentration of 5.9 mg/ml), as measured in this work. In addition, the ethosome zeta potential value increased as a function of THP concentration, from -4.5 to +10.4 when the THP concentration was increased from 0 to 3%. In contrast, THP liposomes were much larger and their charge was not affected by THP. When compared with standard liposomes, ethosomes had a higher entrapment capacity and a greater ability to deliver entrapped fluorescent probe to the deeper layers of skin. The flux of THP through nude mouse skin from THP ethosomes (0.21 mg/cm2 h) was 87, 51 and 4.5 times higher than from liposomes, phosphate buffer and hydroethanolic solution, respectively (p ethosomal system than from liposomes or a control hydroethanolic solution. Our results indicate that the ethosomal THP system may be a promising candidate for transdermal delivery of THP.

  18. Liposomes- and ethosomes-associated distamycins: a comparative study. (United States)

    Cortesi, Rita; Romagnoli, Romeo; Drechsler, Markus; Menegatti, Enea; Zaid, Abdel N; Ravani, Laura; Esposito, Elisabetta


    The present article describes a comparative study of the performances of liposomes and ethosomes as specialized delivery systems for distamycin A (DA) and two of its derivatives. Liposomes and ethosomes were prepared by classical methods, extruded through polycarbonate filters, and characterized in terms of dimensions, morphology, and encapsulation efficiency. It was found that DA was associated with vesicles (either liposomes or ethosomes) by around 16.0%, while both derivatives of DA showed a percentage of association around 80% in the case of liposomes and around 50% in the case of ethosomes. In vitro antiproliferative activity experiments performed on cultured human and mouse leukemic cells demonstrated that vesicles were able to increase the activity of both derivatives of DA. In addition, it was demonstrated that the aging of both liposomes- and ethosomes-associated distamycin suspensions did not heavily influence the vesicle size, while all samples showed a relevant drug leakage with time. Moreover, according to the different physicochemical characteristics of DA and its derivatives (i.e., log P), vesicle-associated DA showed the highest loss of drug with respect to both its derivatives. In conclusion, the enhancement of drug activity expressed by these specialized delivery systems-associated DD could be interesting to obtain an efficient therapeutic effect aimed at reducing or minimizing toxic effects occurring with distamycins administration.

  19. In vitro spectroscopic study of piperine-encapsulated nanosize liposomes. (United States)

    Pentak, Danuta


    Black pepper is a source of effective antioxidants. It contains several powerful antioxidants and is thus one of the most important spices for preventing and curtailing oxidative stress. There is considerable interest in the development of a drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic and amphiphilic molecules. This article focuses on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress. Liposome formulations of piperine were analyzed with various spectroscopic methods. The formulation with the highest entrapment efficiency (90.5%) was formulated with an L-α-phosphatidylcholine dipalmitoyl (DPPC):piperine, 30:1 molar ratio, and total lipid count of 19.47 mg/ml in the final liposomal preparation. The liposome formulation was found to be stable after storage at 4 °C, protected from light, for a minimum of 3 weeks. The incremental process of piperine penetration through the phospholipid membrane was analyzed using the FT-IR, UV-Vis and NMR methods. Temperature stability studies carried out at 37 °C showed the highest percentage of piperine release in the first 3 h of incubation.

  20. Formulation and stabilization of norfloxacin in liposomal preparations. (United States)

    Ahmad, Iqbal; Arsalan, Adeel; Ali, Syed Abid; Bano, Raheela; Munir, Iqra; Sabah, Arif


    A number of liposomal preparations of norfloxacin (NF) containing variable concentrations of phosphatidylcholine (PC) (10.8-16.2mM) have been formulated and an entrapment of NF to the extent of 41.7-56.2% was achieved. The values of apparent first-order rate constants (kobs) for the photodegradation of NF in liposomes (pH7.4) lie in the range of 1.05-2.40×10(-3)min(-1) compared to a value of 8.13×10(-3)min(-1) for the photodegradation of NF in aqueous solution (pH7.4). The values of kobs are a linear function of PC concentration indicating an interaction of PC and NF during the reaction. The second-order rate constant for the photochemical interaction of PC and NF has been determined as 8.92×10(-2)M(-1)min(-1). Fluorescence measurements on NF in liposomes indicate a decrease in fluorescence with an increase in PC concentration as a result of formation of NF(-) species which exhibits poor fluorescence. Dynamic light scattering has shown an increase in the size of NF encapsulated liposomes with an increase in PC concentration. The stabilization of NF in liposomes is achieved by the formation of a charge-transfer complex between NF and PC. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. A "Dock and Lock" Approach to Preparation of Targeted Liposomes. (United States)

    Backer, Marina V; Backer, Joseph M


    We developed a strategy for covalent coupling of targeting proteins to liposomes decorated with a standard adapter protein. This strategy is based on "dock and lock" interactions between two mutated fragments of human RNase I, a 1-15 aa fragment with the R4C amino acid substitution (Cys-tag), and a 21-127-aa fragment with the V118C substitution, (Ad-C). Upon binding to each other, Cys-tag and Ad-C spontaneously form a disulfide bond between the complementary 4C and 118C residues. Therefore, any targeting protein expressed with Cys-tag can be easily coupled to liposomes decorated with Ad-C. Here we describe the preparation of Ad-liposomes followed by coupling them to two Cys-tagged targeted proteins, human vascular endothelial growth factor expressed with N-terminal Cys-tag and a 254-aa long N-terminal fragment of anthrax lethal factor carrying C-terminal Cys-tag. Both proteins retain functional activity after coupling to Ad-C-decorated drug-loaded liposomes. We expect that our "dock and lock" strategy will open new opportunities for development of targeted therapeutic liposomes for research and clinical use.

  2. Propylene glycol liposomes as a topical delivery system for miconazole nitrate: comparison with conventional liposomes. (United States)

    Elmoslemany, Riham M; Abdallah, Ossama Y; El-Khordagui, Labiba K; Khalafallah, Nawal M


    Propylene glycol (PG)-phospholipid vesicles have been advocated as flexible lipid vesicles for enhanced skin delivery of drugs. To further characterize the performance of these vesicles and to address some relevant pharmaceutical issues, miconazole nitrate(MN)-loaded PG nanoliposomes were prepared and characterized for vesicle size, entrapment efficiency, in vitro release, and vesicle stability. An issue of pharmaceutical importance is the time-dependent, dilution-driven diffusion of propylene glycol out of the vesicles. This was addressed by assessing propylene glycol using gas chromatography in the separated vesicles and monitoring its buildup in the medium after repeated dispersion of separated vesicles in fresh medium. Further, the antifungal activity of liposomal formulations under study was assessed using Candida albicans, and their in vitro skin permeation and retention were studied using human skin. At all instances, blank and drug-loaded conventional liposomes were included for comparison. The results provided evidence of controlled MN delivery, constant percent PG uptake in the vesicles (≈45.5%) in the PG concentration range 2.5 to 10%, improved vesicle stability, and enhanced skin deposition of MN with minimum skin permeation. These are key issues for different formulation and performance aspects of propylene glycol-phospholipid vesicles.

  3. Liposomal delivery of radionuclides for cancer diagnostics and radiotherapy

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa

    loading experiments and isothermal titration calorimetry (ITC) measurements. Various chelators, ionophores and lipophilic chelators were tested at different pH and temperature conditions. Liposomes passively accumulate in tumors due to the enhanced permeability and retention (EPR) effect. In Article I......, an in vivo study is presented, where passive tumor accumulation of 64Cu loaded liposomes (64Cu-liposomes) in tumor-bearing mice was quantified directly by PET and computed tomography (CT) imaging. Furthermore, Article I present an evaluation and quantitative measurement of the biodistribution of 64Cu......, a so called “unassisted” loading, excluding any use of ionophores and lipophilic chelators. Project IV presents results from this invention (Patent II), where a presentation of various parameters affecting the efficiency of the unassisted loading method is given. Section 5 summarizes the regulatory...

  4. Trigger release liposome systems: local and remote controlled delivery? (United States)

    Bibi, Sagida; Lattmann, E; Mohammed, Afzal R; Perrie, Yvonne


    Target-specific delivery has become an integral area of research in order to increase bioavailability and reduce the toxic effects of drugs. As a drug-delivery option, trigger-release liposomes offer sophisticated targeting and greater control-release capabilities. These are broadly divided into two categories; those that utilise the local environment of the target site where there may be an upregulation in certain enzymes or a change in pH and those liposomes that are triggered by an external physical stimulus such as heat, ultrasound or light. These release mechanisms offer a greater degree of control over when and where the drug is released; furthermore, targeting of diseased tissue is enhanced by incorporation of target-specific components such as antibodies. This review aims to show the development of such trigger release liposome systems and the current research in this field.

  5. Recent Trends in Multifunctional Liposomal Nanocarriers for Enhanced Tumor Targeting

    Directory of Open Access Journals (Sweden)

    Federico Perche


    Full Text Available Liposomes are delivery systems that have been used to formulate a vast variety of therapeutic and imaging agents for the past several decades. They have significant advantages over their free forms in terms of pharmacokinetics, sensitivity for cancer diagnosis and therapeutic efficacy. The multifactorial nature of cancer and the complex physiology of the tumor microenvironment require the development of multifunctional nanocarriers. Multifunctional liposomal nanocarriers should combine long blood circulation to improve pharmacokinetics of the loaded agent and selective distribution to the tumor lesion relative to healthy tissues, remote-controlled or tumor stimuli-sensitive extravasation from blood at the tumor’s vicinity, internalization motifs to move from tumor bounds and/or tumor intercellular space to the cytoplasm of cancer cells for effective tumor cell killing. This review will focus on current strategies used for cancer detection and therapy using liposomes with special attention to combination therapies.

  6. Liposomal amphotericin B and leishmaniasis: Dose and response

    Directory of Open Access Journals (Sweden)

    Shyam Sundar


    Full Text Available Liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL. It is the treatment of choice for immunocompetent patients in the Mediterranean region and the preferred drug for HIV/VL co-infection. Although there is a regional variation in the susceptibility of the parasite a total dose of 20 mg/kg is effective in immunocompetent patients. Randomized clinical trials of liposomal amphotericin B in the treatment and secondary prophylaxis of HIV-VL coinfected patients is urgently needed to optimize treatment in this subset. With the availability of Liposomal amphotericin B at a preferential pricing in the endemic areas, short course combination therapy can become a viable alternative.

  7. Drug delivery by phospholipase A(2) degradable liposomes

    DEFF Research Database (Denmark)

    Davidsen, Jesper; Vermehren, C.; Frøkjær, S.


    The effect of poly(ethylene glycol)-phospholipid (PE-PEG) lipopolymers on phospholipase A(2) (PLA(2)) hydrolysis of liposomes composed of stearoyl-oleoylphosphatidylcholine (SOPC) was investigated. The PLA(2) lag-time, which is inversely related to the enzymatic activity, was determined by fluore......The effect of poly(ethylene glycol)-phospholipid (PE-PEG) lipopolymers on phospholipase A(2) (PLA(2)) hydrolysis of liposomes composed of stearoyl-oleoylphosphatidylcholine (SOPC) was investigated. The PLA(2) lag-time, which is inversely related to the enzymatic activity, was determined...... by fluorescence, and the zeta-potentials of the liposomes were measured as a function of PE-PEG lipopolymer concentration. A significant decrease in the lag-time, and hence an increase in enzymatic activity, was observed with increasing amounts of the negatively charged PE-PEG lipopolymers incorporated...

  8. Novel methods for the encapsulation of meglumine antimoniate into liposomes

    Directory of Open Access Journals (Sweden)

    F. Frézard


    Full Text Available The antimonial drug, meglumine antimoniate, was successfully encapsulated in dehydration-rehydration vesicles and in freeze-dried empty liposomes (FDELs. High encapsulation efficiencies (from 28 to 58% and low weight ratios of lipids to encapsulated antimony (from 1:0.15 to 1:0.3 were achieved. These formulations, contrary to those obtained by conventional methods, can be stored as intermediate lyophilized forms and reconstituted just before use. The efficacy of FDEL-encapsulated meglumine antimoniate was evaluated in hamsters experimentally infected with Leishmania chagasi. A significant reduction of liver parasite burdens was observed in animals treated with this preparation, when compared to control animals treated with empty liposomes. In contrast, free meglumine antimoniate was found to be inefficient when administered at a comparable dose of antimony. This novel liposome-based meglumine antimoniate formulation appears to be promising as a pharmaceutical product for the treatment of visceral leishmaniasis.

  9. Studies on molecular interactions between puerarin and PC liposomes

    Institute of Scientific and Technical Information of China (English)


    Fluorescence emission spectra, FTIR spectra, zeta potential measurements, and ab initio quantum calculation are used to study the interaction between puerarin and membranes composed of egg phosphatidylcholine (PC) liposome. The hydrophobic interactions cause the puerarin molecule to partition into lipid bilayers with its B-ring, and favor the displacement of acid-base equilibrium of puerarin towards the base form. Due to the hydrogen bond formation between the puerarin hydroxyl groups and polar groups of PC molecules on the water/membrane interface, puerarin can easily intercalate into the organized structure of phospholipids and modulate the membrane function. Our results reveal that the liposome membrane integrity is significantly higher compared with that of empty liposome.

  10. PEG minocycline-liposomes ameliorate CNS autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Wei Hu

    Full Text Available BACKGROUND: Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS. Minocycline, a potent inhibitor of matrix metalloproteinase (MMP-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG minocycline liposomes are effective in treating EAE. FINDINGS: Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs, we determined that PEG minocycline-liposome preparations stabilized with CaCl(2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number. CONCLUSIONS: Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS.

  11. Thermosensitive liposomal drug delivery systems: state of the art review

    Directory of Open Access Journals (Sweden)

    Kneidl B


    Full Text Available Barbara Kneidl,1,2 Michael Peller,3 Gerhard Winter,2 Lars H Lindner,1 Martin Hossann11Department of Internal Medicine III, University Hospital Munich, 2Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, 3Institute for Clinical Radiology, University Hospital Munich, Ludwig-Maximilians University, Munich, GermanyAbstract: Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or high intensity focused ultrasound. In vivo results have demonstrated strong evidence that external targeting is superior over passive targeting achieved by highly stable long-circulating drug formulations like PEGylated liposomal doxorubicin. Up to March 2014, the Web of Science listed 371 original papers in this field, with 45 in 2013 alone. Several formulations have been developed since 1978, with lysolipid-containing, low temperature-sensitive liposomes currently under clinical investigation. This review summarizes the historical development and effects of particular phospholipids and surfactants on the biophysical properties and in vivo efficacy of thermosensitive liposome formulations. Further, treatment strategies for solid tumors are discussed. Here we focus on temperature-triggered intravascular and interstitial drug release. Drug delivery guided by magnetic resonance imaging further adds the possibility of performing online monitoring of a heating focus to calculate locally released drug concentrations and to externally control drug release by steering the heating volume and power. The combination of external targeting with thermosensitive liposomes and magnetic resonance-guided drug delivery will be the unique characteristic of this nanotechnology approach in medicine.Keywords: thermosensitive liposomes, phosphatidyloligoglycerol, hyperthermia, high intensity focused ultrasound, drug delivery, drug targeting

  12. Superresolution and Fluorescence Dynamics Evidence Reveal That Intact Liposomes Do Not Cross the Human Skin Barrier

    DEFF Research Database (Denmark)

    Dreier, Jes; Sørensen, Jens A; Brewer, Jonathan R


    In this study we use the combination of super resolution optical microscopy and raster image correlation spectroscopy (RICS) to study the mechanism of action of liposomes as transdermal drug delivery systems in human skin. Two different compositions of liposomes were applied to newly excised human...... skin, a POPC liposome and a more flexible liposome containing the surfactant sodium cholate. Stimulated emission depletion microscopy (STED) images of intact skin and cryo-sections of skin treated with labeled liposomes were recorded displaying an optical resolution low enough to resolve the 100 nm...

  13. Size and stability of liposomes: a possible role of hydration and osmotic forces. (United States)

    Sabín, J; Prieto, G; Ruso, J M; Hidalgo-Alvarez, R; Sarmiento, F


    Dynamic light scattering and electrophoretic mobility measurements have been used to characterize the size, size distribution and zeta potentials (zeta-potentials) of egg yolk phosphatidylcholine (EYPC) liposomes in the presence of monovalent ions ( Na(+) and K(+)). To study the stability of liposomes the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory has been extended by introducing the hydrated radius of the adsorbed ions onto the liposome surfaces. The decrease of liposome size is explained on the basis of the membrane impermeability to some ions which generate osmotic forces, which leads to evacuate water from liposome inside.

  14. Assembly of Liposomes Controlled by Triple Helix Formation

    DEFF Research Database (Denmark)

    Vogel, Stefan; Jakobsen, Ulla


    analysis is monitored by ultraviolet spectroscopy at sub-micromolar concentrations and compared to regular thermal denaturation assays in the absence of liposomes. We report on triplex forming oligonucleotides (TFOs) based on DNA and locked nucleic acid (LNA)/DNA hybrid building blocks and different target...... analysis (NTA) and dynamic light scattering (DLS) show independently from ultraviolet spectroscopy experiments the formation of liposome aggregates.......Attachment of DNA to the surface of different solid nanoparticles (e.g. gold- and silica nanoparticles) is well established and a number of DNA-modified solid nanoparticle systems have been applied to thermal denaturation analysis of oligonucleotides. We report herein the non...

  15. Potential antitumor activity of novel DODAC/PHO-S liposomes (United States)

    Luna, Arthur Cássio de Lima; Saraiva, Greice Kelle Viegas; Filho, Otaviano Mendonça Ribeiro; Chierice, Gilberto Orivaldo; Neto, Salvador Claro; Cuccovia, Iolanda Midea; Maria, Durvanei Augusto


    In recent studies, we showed that synthetic phosphoethanolamine (PHO-S) has a great potential for inducing cell death in several tumor cell lines without damage to normal cells. However, its cytotoxic effect and selectivity against tumor cells could increase with encapsulation in cationic liposomes, such as dioctadecyldimethylammonium chloride (DODAC), due to electrostatic interactions between these liposomes and tumor cell membranes. Our aim was to use cationic liposomes to deliver PHO-S and to furthermore maximize the therapeutic effect of this compound. DODAC liposomes containing PHO-S (DODAC/PHO-S), at concentrations of 0.3–2.0 mM, prepared by ultrasonication, were analyzed by scanning electron microscopy (SEM) and dynamic light scattering. The cytotoxic effect of DODAC/PHO-S on B16F10 cells, Hepa1c1c7 cells, and human umbilical vein endothelial cells (HUVECs) was assessed by MTT assay. Cell cycle phases of B16F10 cells were analyzed by flow cytometry and the morphological changes by SEM, after treatment. The liposomes were spherical and polydisperse in solution. The liposomes were stable, presenting an average of ∼50% of PHO-S encapsulation, with a small reduction after 40 days. DODAC demonstrated efficient PHO-S delivery, with the lowest values of IC50% (concentration that inhibits 50% of the growth of cells) for tumor cells, compared with PHO-S alone, with an IC50% value of 0.8 mM for B16F10 cells and 0.2 mM for Hepa1c1c7 cells, and without significant effects on endothelial cells. The Hepa1c1c7 cells showed greater sensitivity to the DODAC/PHO-S formulation when compared to B16F10 cells and HUVECs. The use of DODAC/PHO-S on B16F10 cells induced G2/M-phase cell cycle arrest, with the proportion significantly greater than that treated with PHO-S alone. The morphological analysis of B16F10 cells by SEM showed changes such as “bleb” formation, cell detachment, cytoplasmic retraction, and apoptotic bodies after DODAC/PHO-S treatment. Cationic liposomal

  16. Antibodies to Phospholipids and Liposomes: Binding of Antibodies to Cells (United States)


    LIPOSOMES: BINDING OF ANTIBODIES TO CELLS 12. PERSONAL AUTHOR(S) W.E. FOGLER , G. M. SWARTZ, AND C.R. ALVING 13a TYPE OF REPORT 13b. TIME COVERED 14. DATE...Elsevier BBA 73693 Antibodies to phospholipids and liposomes: binding of antibodies to cells William E. Fogler *, Glenn M. Swartz, Jr. and Carl R. Alving...Immunol. 21. Research Associateship from the U.S. National 12863-86812Hall. T. and Esser, K. (1984) 3. Immunol. 132. 2059-2063 Research Council. 13 Fogler

  17. Lipophilic drug transfer between liposomal and biological membranes

    DEFF Research Database (Denmark)

    Fahr, Alfred; van Hoogevest, Peter; Kuntsche, Judith


    is described as solubility of a drug in phospholipid membranes and the kinetics of transfer of a lipophilic drug between membranes. Finally, the consequences of these two factors on the design of lipid-based carriers for oral, as well as parenteral use, for lipophilic drugs and lead selection of oral...... lipophilic drugs is described. Since liposomes serve as model-membranes for natural membranes, the assessment of lipid solubility and transfer kinetics of lipophilic drug using liposome formulations may additionally have predictive value for bioavailability and biodistribution and the pharmacokinetics...

  18. Pirfenidone-loaded liposomes for lung targeting: preparation and in vitro/in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Meng H


    Full Text Available Hui Meng, Yong XuDepartment of Pharmaceuticals, 85th People’s Liberation Army Hospital, Shanghai, People’s Republic of China Background: The purpose of this study was to develop novel pirfenidone (PFD-loaded liposomes for targeting to the lung.Methods: The liposomes were prepared by the film hydration method, and their in vitro/vivo characteristics were evaluated.Results: The PFD liposomes appeared visually as green to yellowish suspensions and were spherical in shape. The particle size was 582.3±21.6 nm and the entrapment efficiency was relatively high (87.2%±5.7%. The liposomes showed typical sustained and prolonged drug-release behavior in vitro and fitted well with the Weibull distribution equation. The relatively slower time taken to reach a minimal plasma PFD concentration in vivo suggests that PFD liposomes have a sustained-release profile, which is consistent with the results of the in vitro release study. The PFD liposomes showed the largest area under the curve for the lung. The high distribution of PFD achieved in the lungs using this liposomal formulation may be explained by physical entrapment of the liposomes in the vascular network of the lung. Histopathological results indicated that liposomal PFD could alleviate pathological injury in lung tissue.Conclusion: This liposomal formulation can enable sustained release of PFD and increase targeting to the lung. Keywords: pirfenidone, liposomes, lung targeting, in vivo, histopathological 

  19. Preparation of human hepatocellular carcinoma-targeted liposome microbubbles and their immunological properties

    Institute of Scientific and Technical Information of China (English)

    Ai-Na Bian; Yun-Hua Gao; Kai-Bin Tan; Ping Liu; Gong-Jun Zeng; Xin Zhang; Zheng Liu


    AIM: To prepare the human hepatocellular carcinoma.(HCC)-targeted liposome microbubbles and to investigate their immunological properties.METHODS: Human hepatocarcinoma specific monoclonal antibody HAb18 was attached to the surface of home-made liposome microbubbles by static attraction to prepare the targeted liposome microbubbles. The combination of HAb18 with liposome microbubbles was confirmed by the slide agglutination test and immunofluorescent assay. Their immunological activity was measured by ELISA. Rosette formation test, rosette formation blocking test and immunofluorescent assay were used to identify the specific binding of targeted liposome microbubbles to SMMC-7721 hepatoma cells, and cytotoxicity assay was used to detect their effect on human hepatocytes.RESULTS: The targeted liposome microbubbles were positive in the slide agglutination test and immunofluorescent assay. ELISA indicated that the immunological activity of HAb18 on the liposome microbubbles was similar to that of free HAb18. SMMC-7721 cells were surrounded by the targeting liposome microbubbles to form rosettes, while the control SGC-7901 gastric cancer cells were not. Proliferation of SMMC-7721 cells and normal human hepatocytes was not influenced by the targeted liposome microbubbles.CONCLUSION: The targeted liposome microbubbles with a high specific biological activity have been successfully prepared, which specifically bind to human hepatocarcinoma cells, and are non-cytotoxic to hepatocytes. These results indicate that the liposome microbubbles can be used as a HCC-targeted ultrasound contrast agent that may enhance ultrasound images and thus improve the diagnosis of HCC,especially at the early stage.

  20. Factorial design studies of antiretroviral drug-loaded stealth liposomal injectable: PEGylation, lyophilization and pharmacokinetic studies (United States)

    Sudhakar, Beeravelli; Krishna, Mylangam Chaitanya; Murthy, Kolapalli Venkata Ramana


    The aim of the present study was to formulate and evaluate the ritonavir-loaded stealth liposomes by using 32 factorial design and intended to delivered by parenteral delivery. Liposomes were prepared by ethanol injection method using 32 factorial designs and characterized for various physicochemical parameters such as drug content, size, zeta potential, entrapment efficiency and in vitro drug release. The optimization process was carried out using desirability and overlay plots. The selected formulation was subjected to PEGylation using 10 % PEG-10000 solution. Stealth liposomes were characterized for the above-mentioned parameters along with surface morphology, Fourier transform infrared spectrophotometer, differential scanning calorimeter, stability and in vivo pharmacokinetic studies in rats. Stealth liposomes showed better result compared to conventional liposomes due to effect of PEG-10000. The in vivo studies revealed that stealth liposomes showed better residence time compared to conventional liposomes and pure drug solution. The conventional liposomes and pure drug showed dose-dependent pharmacokinetics, whereas stealth liposomes showed long circulation half-life compared to conventional liposomes and pure ritonavir solution. The results of statistical analysis showed significance difference as the p value is (<0.05) by one-way ANOVA. The result of the present study revealed that stealth liposomes are promising tool in antiretroviral therapy.

  1. The cellular internalization of liposome encapsulated protoporphyrin IX by HeLa cells. (United States)

    Przybylo, Magdalena; Glogocka, Daria; Dobrucki, Jerzy W; Fraczkowska, Kaja; Podbielska, Halina; Kopaczynska, Marta; Borowik, Tomasz; Langner, Marek


    The proper lipid composition of liposomes designed to carry drugs determines their surface properties ensuring their accumulation within selected tissue. The electrostatic potential and surface topology of liposomes affect the internalization by single cells. The high-resolution imaging of cancer cells and the distribution of protoporphyrin-loaded liposomes within the cytoplasm and its dependence on the liposome surface properties are presented. In the paper, HeLa cells were used to investigate the uptake of porphyrin-loaded liposomes and liposomes alone by means of confocal and differential interference contrast microscopies. The effect of liposomes surface electrostatic potential and surface topology on their intracellular distribution was evaluated. The time evolution of the intracellular distribution of liposomes labelled with Rhodamine-PE was examined on HeLa cells. These studies allow for the identification of the liposome lipid composition so the efficient delivery of the active substance to cancer cells will be achieved. The obtained results showed that neutral PC-liposomes are the most efficiently internalized by HeLa cells. Moreover, results showed that properties of liposomes affect not only the internalization efficiency of the photosensitizer but also its distribution within the cells, as revealed by colocalization measurements.

  2. Dopamine-loaded liposome and its application in electrochemical DNA biosensor. (United States)

    Mahmoudi-Badiki, Tohid; Alipour, Esmaeel; Hamishehkar, Hamed; Golabi, Seyed Mahdi


    In this study, disruption and lyophilization-rehydration of dopamine-loaded liposome and its application in electrochemical DNA biosensor was investigated. The liposomes containing soyphosphatidylcholine and cholesterol were prepared through thin-layer hydration. First, an investigation was carried out to find an appropriate lysing agent for disruption of prepared liposomes. Differential pulse voltammetry, as a high sensitive electrochemical technique, was used along with a multi-walled carbon nanotubes modified glassy carbon electrode for sensitive electrochemical detection of released dopamine from disrupted liposomes. Various lysing agents were investigated and finally, the disruption of liposomes using methanol was selected without any surfactant, because of its least fouling effect. Then, lyophilization of dopamine-loaded liposomes was carried out using sucrose as cryoprotectant. The electrochemical studies of lyophilized liposomes showed that the remained dopamine in sucrose-protected liposomes was higher than sucrose-free liposomes. Furthermore, sucrose has no interference in electrochemical studies. Then, with the addition of biotin-X-DHPE to liposome formulation, the lyophilized sucrose protected dopamine-loaded biotin-tagged liposomes were prepared and the feasibility of application of them in electrochemical DNA biosensor was investigated as signal enhancer and verified for detection of oligonucleotides.

  3. Cooperative antioxidative effects of zein hydrolysates with sage (Salvia officinalis) extract in a liposome system. (United States)

    Li, Yuanyuan; Liu, Haotian; Han, Qi; Kong, Baohua; Liu, Qian


    This study investigated the cooperative antioxidative effects of sage extract (SE) and zein hydrolysates (ZH). The combination of 3mg/ml ZH and 10μg/ml SE exhibited a significant synergism in inhibition of the formation of thiobarbituric acid-reactive substances and provided superior protection of liposomes against oxidation. Zeta-potential results revealed that the interactions between liposomes and ZH were electrostatic interactions. Particle size determination further proved that ZH and SE added to oxidized liposomes significantly decreased the mean particle size. Confocal laser scanning microscopy revealed that when ZH was present in the liposome oxidizing system, the droplet sizes were obviously decreased compared to oxidized samples. ZH dispersed more uniformly and the interfacial membrane was more compact in the ZH-SE liposome. Transmission electron microscopy conveyed that the ZH-SE complex around the liposome particles could form a denser network structure, preventing radicals and oxidants from the approach of the liposomes.

  4. Molecular Dynamics Simulations and Empirical Observations on Soy Lecithin Liposome Preparation

    Directory of Open Access Journals (Sweden)

    Rini Dwiastuti


    Full Text Available Soy lecithin is a phospholipid often used in liposome formulations. Determination of water and phospholipid composition is one of the problems in the liposome formulation. This study is using molecular dynamics simulation and empirical observation in producing liposome preparations. Phospholipids 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine (DLPE were objected in molecular dynamics simulations using Coarse Grained Molecular Dynamics (CGMD approaches. The result showed that the molecular dynamic simulations could be employed to predict the liposome size. The molecular dynamic simulations resulted in liposome size of 71.22 ± 2.54 nm, which was located within the range of the liposome size resulted from the empirical observations (95.99 ± 43.02 nm. Moreover, similar liposome forms were observed on both results of molecular dynamics simulations and empirical approaches.


    Directory of Open Access Journals (Sweden)

    O. V. Khrobatenko


    Full Text Available Liposomal form of adenosine-5-triphosphate (ATP for oral applying was studied. The methods of obtaining and determining the size of the liposomes, the definition of ATP percentage content in liposomes were proposed. The effect of liposomal form of ATP on physical performance of laboratory animals by swimming to the limit of exhaustion was studied. It was shown that using of the liposomal form as compared with free ATP (in a similar dose promoted the increased efficiency of laboratory animals. Application of liposomal form occurring at single administration for 6 days at a dose of 30 mg/kg facilated a 62% increase of efficiency, and 60 mg/kg did 76%, while consumption of liposomal form of ATP for 12 days did 64% and 93%, respectively.

  6. Exploring Cellular Interactions of Liposomes Using Protein Corona Fingerprints and Physicochemical Properties. (United States)

    Bigdeli, Arafeh; Palchetti, Sara; Pozzi, Daniela; Hormozi-Nezhad, Mohammad Reza; Baldelli Bombelli, Francesca; Caracciolo, Giulio; Mahmoudi, Morteza


    To control liposomes fate and transport upon contact with biofluids, it is essential to consider several parameters affecting the synthetic and biological identity of liposomes, as well as liposome-protein corona (PC) aspects. As a powerful tool in this data mining adventure, quantitative structure-activity relationship (QSAR) approach is used to correlate physicochemical properties of liposomes and their PC fingerprints to multiple quantified biological responses. In the present study, the relationship between cellular interactions of a set of structurally diverse liposomal formulations and their physicochemical and PC properties has been investigated via linear and nonlinear QSAR models. Significant parameters affecting cellular uptake and cell viability of liposomes in two important cancer cell lines (PC3 and HeLa) have been identified. The developed QSARs have the capacity to be implemented in advanced targeted delivery of liposomal drugs.

  7. Length of hydrocarbon chain influences location of curcumin in liposomes: Curcumin as a molecular probe to study ethanol induced interdigitation of liposomes. (United States)

    El Khoury, Elsy; Patra, Digambara


    Using fluorescence quenching of curcumin in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes by brominated derivatives of fatty acids, the location of curcumin has been studied, which indicates length of hydrocarbon chain has an effect on the location of curcumin in liposomes. Change of fluorescence intensity of curcumin with temperature in the presence of liposomes helps to estimate the phase transition temperature of these liposomes, thus, influence of cholesterol on liposome properties has been studied using curcumin as a molecule probe. The cooperativity due to the interactions between the hydrocarbon chains during melting accelerates the phase transition of DPPC liposomes in the presence of high percentage of cholesterol whereas high percentage of cholesterol generates a rather rigid DMPC liposome over a wide range of temperatures. We used ethanol to induce interdigitation between the hydrophobic chains of the lipids and studied this effect using curcumin as fluorescence probe. As a result of interdigitation, curcumin fluorescence is quenched in liposomes. The compact arrangement of the acyl chains prevents curcumin from penetrating deep near the midplane. In the liquid crystalline phase ethanol introduces a kind of order to the more fluid liposome, and does not leave space for curcumin to be inserted away from water.

  8. Development and characterization of an innovative heparin coating to stabilize and protect liposomes against adverse immune reactions. (United States)

    Duehrkop, Claudia; Leneweit, Gero; Heyder, Christoph; Fromell, Karin; Edwards, Katarina; Ekdahl, Kristina N; Nilsson, Bo


    Liposomes have been recognized as excellent drug delivery systems, but when they come in direct contact with different blood components they may trigger an immediate activation of the innate immune system. The aim of the present study was to produce long-circulating, blood-compatible liposomes by developing a construct of liposomes covered by a novel unique heparin complex (CHC; 70 heparin molecules per complex) to avoid recognition by the innate immune system. Unilamellar, cationic liposomes were produced by hand extrusion through a 100-nm polycarbonate membrane. Coating of liposomes with the macromolecular CHC was accomplished by electrostatic interactions. Dynamic light scattering as well as QCM-D measurements were used to verify the electrostatic deposition of the negatively charged CHC to cationic liposomes. The CHC-coated liposomes did not aggregate when in contact with lepirudin anti-coagulated plasma. Unlike previous attempts to coat liposomes with heparin, this technique produced freely moveable heparin strands sticking out from the liposome surface, which exposed AT binding sites reflecting the anticoagulant potentials of the liposomes. In experiments using lepirudin-anticoagulated plasma, CHC-coated liposomes, in contrast to non-coated control liposomes, did not activate the complement system, as evidenced by low C3a and sC5b-9 generation and reduced leakage from the liposomes. In conclusion, we show that liposomes can be successfully coated with the biopolymer CHC, resulting in biocompatible and stable liposomes that have significant application potential.

  9. Receptor versus non-receptor mediated clearance of liposomes

    NARCIS (Netherlands)

    Scherphof, GL; Kamps, JAAM


    Numerous studies have appeared over the years dealing with liposome-cell interaction mechanisms, most of them performed under in vitro conditions with isolated cell populations or cell lines. It is remarkable that, nonetheless, there hardly seem to exist established and generally accepted views on h

  10. Protein antigen adsorption to the DDA/TDB liposomal adjuvant

    DEFF Research Database (Denmark)

    Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber;


    Understanding the nature of adjuvant-antigen interactions is important for the future design of efficient and safe subunit vaccines, but remains an analytical challenge. We studied the interactions between three model protein antigens and the clinically tested cationic liposomal adjuvant composed...

  11. Liposomal photosensitizers: potential platforms for anticancer photodynamic therapy

    Directory of Open Access Journals (Sweden)

    L.A. Muehlmann


    Full Text Available Photodynamic therapy is a well-established and clinically approved treatment for several types of cancer. Antineoplastic photodynamic therapy is based on photosensitizers, i.e., drugs that absorb photons translating light energy into a chemical potential that damages tumor tissues. Despite the encouraging clinical results with the approved photosensitizers available today, the prolonged skin phototoxicity, poor selectivity for diseased tissues, hydrophobic nature, and extended retention in the host organism shown by these drugs have stimulated researchers to develop new formulations for photodynamic therapy. In this context, due to their amphiphilic characteristic (compatibility with both hydrophobic and hydrophilic substances, liposomes have proven to be suitable carriers for photosensitizers, improving the photophysical properties of the photosensitizers. Moreover, as nanostructured drug delivery systems, liposomes improve the efficiency and safety of antineoplastic photodynamic therapy, mainly by the classical phenomenon of extended permeation and retention. Therefore, the association of photosensitizers with liposomes has been extensively studied. In this review, both current knowledge and future perspectives on liposomal carriers for antineoplastic photodynamic therapy are critically discussed.

  12. 64Cu loaded liposomes as positron emission tomography imaging agents

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Binderup, Tina; Rasmussen, Palle


    We have developed a highly efficient method for utilizing liposomes as imaging agents for positron emission tomography (PET) giving high resolution images and allowing direct quantification of tissue distribution and blood clearance. Our approach is based on remote loading of a copper-radionuclid...

  13. In vivo toxicity of cationic micelles and liposomes

    DEFF Research Database (Denmark)

    Knudsen, Kristina Bram; Northeved, Helle; Ek, Pramod Kumar


    This study investigated toxicity of nanocarriers comprised of cationic polymer and lipid components often used in gene and drug delivery, formulated as cationic micelles and liposomes. Rats were injected intravenously with 10, 25 or 100 mg/kg and sacrificed after 24 or 48 h, or 24 h after the last...

  14. Enhancing Methotrexate Tolerance with Folate Tagged Liposomes in Arthritic Mice. (United States)

    Nogueira, Eugénia; Lager, Franck; Le Roux, Delphine; Nogueira, Patrícia; Freitas, Jaime; Charvet, Celine; Renault, Gilles; Loureiro, Ana; Almeida, Catarina R; Ohradanova-Repic, Anna; Machacek, Christian; Bernardes, Gonçalo J L; Moreira, Alexandra; Stockinger, Hannes; Burnet, Michael; Carmo, Alexandre M; Gomes, Andreia C; Preto, Ana; Bismuth, Georges; Cavaco-Paulo, Artur


    Methotrexate is the first line of treatment of rheumatoid arthritis. Since many patients become unresponsive to methotrexate treatment, only very expensive biological therapies are effective and increased methotrexate tolerance strategies need to be identified. Here we propose the encapsulation of methotrexate in a new liposomal formulation using a hydrophobic fragment of surfactant protein conjugated to a linker and folate to enhance their tolerance and efficacy. In this study we aim to evaluate the efficiency of this system to treat rheumatoid arthritis, by targeting folate receptor β present at the surface of activated macrophages, key effector cells in this pathology. The specificity of our liposomal formulation to target folate receptor β was investigated both in vitro as in vivo using a mouse model of arthritis (collagen-induced arthritis in DBA/1J mice strain). In both systems, the liposomal constructs were shown to be highly specific and efficient in targeting folate receptor β. These liposomal formulations also significantly increase the clinical benefit of the encapsulated methotrexate in vivo in arthritic mice, together with reduced expression of CD39 and CD73 ectonucleotidases by joint-infiltrating macrophages. Thus, our formulation might be a promising cost effective way to treat rheumatoid arthritis and delay or reduce methotrexate intolerance.

  15. LeciPlex, invasomes, and liposomes: A skin penetration study. (United States)

    Shah, Sanket M; Ashtikar, Mukul; Jain, Ankitkumar S; Makhija, Dinesh T; Nikam, Yuvraj; Gude, Rajiv P; Steiniger, Frank; Jagtap, Aarti A; Nagarsenker, Mangal S; Fahr, Alfred


    The present study compares three vesicular systems, cationic LeciPlex, invasomes, and conventional liposomes for their ability to deliver drugs deep into the skin. Skin penetration ability of the three vesicular systems was studied for two drugs namely idebenone (antioxidant/anticancer) and azelaic acid (antiacne). All systems showed sizes in nanometer range with small polydispersity indices. Vesicular systems were characterized by CryoTEM studies to understand the differences in morphology of the vesicular systems. Ex vivo human skin penetration studies suggested a pattern in penetration of drugs in different layers of the skin: LeciPlex showed higher penetration for idebenone whereas invasomes showed higher penetration of azelaic acid. Ex vivo study using a fluorescent dye (DiI) was performed to understand the differences in the penetration behavior of the three vesicular systems on excised human skin. In vitro cytotoxicity studies on B16F10 melanoma cell lines revealed, when loaded with idebenone, LeciPlex formulations had the superior activity followed by invasomes and liposomes. In vitro antimicrobial study of azelaic acid loaded systems on Propionibacterium acne revealed high antimicrobial activity for DDAB leciplex followed by almost equal activity for invasomes and CTAB LeciPlex followed by liposomes. Whereas antiacne efficacy study in rats for azelaic acid loaded systems, invasomes exhibited the best antiacne efficacy followed by liposomes and LeciPlex.

  16. Soft Interaction in Liposome Nanocarriers for Therapeutic Drug Delivery

    Directory of Open Access Journals (Sweden)

    Domenico Lombardo


    Full Text Available The development of smart nanocarriers for the delivery of therapeutic drugs has experienced considerable expansion in recent decades, with the development of new medicines devoted to cancer treatment. In this respect a wide range of strategies can be developed by employing liposome nanocarriers with desired physico-chemical properties that, by exploiting a combination of a number of suitable soft interactions, can facilitate the transit through the biological barriers from the point of administration up to the site of drug action. As a result, the materials engineer has generated through the bottom up approach a variety of supramolecular nanocarriers for the encapsulation and controlled delivery of therapeutics which have revealed beneficial developments for stabilizing drug compounds, overcoming impediments to cellular and tissue uptake, and improving biodistribution of therapeutic compounds to target sites. Herein we present recent advances in liposome drug delivery by analyzing the main structural features of liposome nanocarriers which strongly influence their interaction in solution. More specifically, we will focus on the analysis of the relevant soft interactions involved in drug delivery processes which are responsible of main behaviour of soft nanocarriers in complex physiological fluids. Investigation of the interaction between liposomes at the molecular level can be considered an important platform for the modeling of the molecular recognition processes occurring between cells. Some relevant strategies to overcome the biological barriers during the drug delivery of the nanocarriers are presented which outline the main structure-properties relationships as well as their advantages (and drawbacks in therapeutic and biomedical applications.

  17. Mechanisms of reduction of antitumor drug toxicity by liposome encapsulation

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, Y. E.; Hanson, W. R.; Bharucha, J.; Ainsworth, E. J.; Jaroslow, B.


    The antitumor drug Actinomycin D is effective against the growth of some human solid tumors but its use is limited by its extreme toxicity. The development of a method of administering Act. D to reduce its systemic toxicity by incorporating the drug within liposomes reduced its toxicity but its tumoricidal activity was retained.

  18. Incorporation of Amphiphilic Cyclodextrins into Liposomes as Artificial Receptor Units

    NARCIS (Netherlands)

    Kauscher, Ulrike; Stuart, Marc C. A.; Druecker, Patrick; Galla, Hans-Joachim; Ravoo, Bart Jan


    In this article, we describe the introduction of amphiphilic beta-cyclodextrins into liposomes to act as artificial receptor units. Using dynamic light scattering, dye encapsulation, and cryogenic transmission electron microscopy, we show that amphiphilic beta-cyclodextrins can be mixed in any propo

  19. Gemcitabine-loaded liposomes: rationale, potentialities and future perspectives

    Directory of Open Access Journals (Sweden)

    Federico C


    Full Text Available Cinzia Federico, Valeria M Morittu, Domenico Britti, Elena Trapasso, Donato CoscoDepartment of Health Sciences, Building of BioSciences, University “Magna Græcia” of Catanzaro, Campus Universitario “S Venuta”, Germaneto, ItalyAbstract: This review describes the strategies used in recent years to improve the biopharmaceutical properties of gemcitabine, a nucleoside analog deoxycytidine antimetabolite characterized by activity against many kinds of tumors, by means of liposomal devices. The main limitation of using this active compound is the rapid inactivation of deoxycytidine deaminase following administration in vivo. Consequently, different strategies based on its encapsulation/complexation in innovative vesicular colloidal carriers have been investigated, with interesting results in terms of increased pharmacological activity, plasma half-life, and tumor localization, in addition to decreased side effects. This review focuses on the specific approaches used, based on the encapsulation of gemcitabine in liposomes, with particular attention to the results obtained during the last 5 years. These approaches represent a valid starting point in the attempt to obtain a novel, commercializable drug formulation as already achieved for liposomal doxorubicin (Doxil®, Caelyx®.Keywords: gemcitabine, liposomes, multidrug, poly(ethylene glycol, tumors

  20. A new method for liposome preparation using a membrane contactor. (United States)

    Jaafar-Maalej, Chiraz; Charcosset, Catherine; Fessi, Hatem


    In this article, we present a novel, scalable liposomal preparation technique suitable for the entrapment of pharmaceutical agents into liposomes. This new method is based on the ethanol-injection technique and uses a membrane contactor module, specifically designed for colloidal system preparation. In order to investigate the process, the influence of key parameters on liposome characteristics was studied. It has been established that vesicle-size distribution decreased with a decrease of the organic-phase pressure, an increase of the aqueous-phase flow rate, and a decrease of the phospholipid concentration. Additionally, special attention was paid on reproducibility and long-term stability of lipid vesicles, confirming the robustness of the membrane contactor-based technique. On the other hand, drug-loaded liposomes were prepared and filled with two hydrophobic drug models. High entrapment-efficiency values were successfully achieved for indomethacin (63%) and beclomethasone dipropionate (98%). Transmission electron microscopy images revealed nanometric quasispherical-shaped multilamellar vesicles (size ranging from 50 to 160 nm).

  1. Single cell targeting using plasmon resonant gold-coated liposomes (United States)

    Leung, Sarah J.; Romanowski, Marek


    We have developed an experimental system with the potential for the delivery and localized release of an encapsulated agent with high spatial and temporal resolution. We previously introduced liposome-supported plasmon resonant gold nanoshells; in this composite structure, the liposome allows for the encapsulation of substances, such as therapeutic agents, neurotransmitters, or growth factors, and the plasmon resonant structure facilitates the rapid release of encapsulated contents upon laser light illumination. More recently, we demonstrated that these gold-coated liposomes are capable of releasing their contents in a spectrally-controlled manner, where plasmon resonant nanoparticles only release content upon illumination with a wavelength of light matching their plasmon resonance band. We now show that this release mechanism can be used in a biological setting to deliver a peptide derivative of cholecystokinin to HEK293 cells overexpressing the CCK2 receptor. Using directed laser light, we may enable localized release from gold-coated liposomes to enable accurate perturbation of cellular functions in response to released compounds; this system may have possible applications in signaling pathways and drug discovery.

  2. D-myo-inositol derivatives alter liposomal membrane fluidity

    NARCIS (Netherlands)

    Brailoiu, E; Margineanu, A; Toma, CP; Filipeanu, CM; Rusu, [No Value; Branisteanu, DD

    We investigated the effect on membrane fluidity induced by D-myo-inositol derivatives (IP3, IP4, IP5, IP6). Fluidity was determined as the anisotropy of fluorescence polarisation fi om liposome model membranes labelled with DPH (1,6-diphenyl-1,3,5 hexatriene). IP3 (10(-10) to 10(-5) M) increased the

  3. Drug delivery by phospholipase A(2) degradable liposomes

    DEFF Research Database (Denmark)

    Davidsen, Jesper; Vermehren, C.; Frøkjær, S.


    The effect of poly(ethylene glycol)-phospholipid (PE-PEG) lipopolymers on phospholipase A(2) (PLA(2)) hydrolysis of liposomes composed of stearoyl-oleoylphosphatidylcholine (SOPC) was investigated. The PLA(2) lag-time, which is inversely related to the enzymatic activity, was determined...

  4. Some factors affecting the valinomycin-induced leak from liposomes

    NARCIS (Netherlands)

    Blok, M.C.; Gier, J. de; Deenen, L.L.M. van


    Experiments dealing with the valinomycin-induced K+ leak from egg lecithin liposomes have demonstrated the importance of the enclosed anion. Except when lipophilic anions are enclosed, the addition of both valinomycin and a uncoupler, e.g. carbonylcyanide p-trifluoromethoxyphenylhydrazone, is necess

  5. Toxicity of doxorubicin entrapped within long-circulating liposomes

    NARCIS (Netherlands)

    Daemen, T; Regts, J; Meesters, M; TenKate, MT; BakkerWoudenberg, IAJM; Scherphof, GL


    We studied the effect of doxorubicin entrapped within long-circulating liposomes (Dox-LCL) on the phagocytic capacity and bacterial blood clearance capacity of rat liver macrophages. Dox-LCL (125 nm in diameter) were composed of egg phosphatidylcholine (PC), cholesterol (CH) and poly(ethyleneglycol)

  6. Liposomal Formulation of Retinoids Designed for Enzyme Triggered Release

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob; Adolph, Sidsel Kramshøj; Subramanian, Arun Kumar;


    The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A(2) IIA and have potential in liposomal drug delivery targeting tumors. We have synthesi...

  7. D-myo-inositol derivatives alter liposomal membrane fluidity

    NARCIS (Netherlands)

    Brailoiu, E; Margineanu, A; Toma, CP; Filipeanu, CM; Rusu, [No Value; Branisteanu, DD


    We investigated the effect on membrane fluidity induced by D-myo-inositol derivatives (IP3, IP4, IP5, IP6). Fluidity was determined as the anisotropy of fluorescence polarisation fi om liposome model membranes labelled with DPH (1,6-diphenyl-1,3,5 hexatriene). IP3 (10(-10) to 10(-5) M) increased the

  8. Liposomal formulations of prilocaine, lidocaine and mepivacaine prolong analgesic duration. (United States)

    Cereda, Cíntia Maria Saia; Brunetto, Giovana Bruschini; de Araújo, Daniele Ribeiro; de Paula, Eneida


    A laboratory investigation was undertaken to compare the in vivo antinociceptive effects of 2% liposomal formulations of prilocaine (PLC), lidocaine (LDC) and mepivacaine (MVC) compared to plain solutions of each of these three local anesthetics. Large unilamellar vesicles were prepared by extrusion (400 nm), at pH 7.4. The membrane/water partition coefficients were obtained from encapsulation efficiency values, after incorporation of each local anesthetic to the vesicles. The anesthetic effect of each liposomal formulation was compared to the respective local anesthetic solution in water, using the infraorbital nerve-blockade test, in rats. The partition coefficients were: 57 for PLC, 114 for LDC and 93 for MVC. In vivo results showed that local anesthetic-free liposomes, used as control, had no analgesic effect. In contrast, the encapsulated formulations induced increased intensities of total anesthetic effect (35.3%, 26.1% and 57.1%) and time for recovery (percentage increases of 30%, 23.1% and 56%), respectively, for PLC, LDC and MVC when compared to the plain solutions (P Mepivacaine was affected to the greatest extent, while LDC benefited least from liposome encapsulation, possibly due to greater vasodilatory properties of LDC.

  9. Liposome functionalization with copper-free "click chemistry"

    NARCIS (Netherlands)

    Oude Blenke, Erik; Klaasse, Gruson; Merten, Hannes; Plückthun, Andreas; Mastrobattista, Enrico|info:eu-repo/dai/nl/228061105; Martin, Nathaniel I.|info:eu-repo/dai/nl/314123083


    The modification of liposomal surfaces is of interest for many different applications and a variety of chemistries are available that makes this possible. A major disadvantage of commonly used coupling chemistries (e.g. maleimide-thiol coupling) is the limited control over the site of conjugation in

  10. Coupling of Ligands to the Liposome Surface by Click Chemistry. (United States)

    Spanedda, Maria Vittoria; De Giorgi, Marcella; Hassane, Fatouma Saïd; Schuber, Francis; Bourel-Bonnet, Line; Frisch, Benoît


    Click chemistry represents a new bioconjugation strategy that can be used to conveniently attach various ligands to the surface of preformed liposomes. This efficient and chemoselective reaction involves a Cu(I)-catalyzed azide-alkyne cycloaddition which can be performed under mild experimental conditions in aqueous media. Here we describe the application of a model click reaction to the conjugation, in a single step, of unprotected α-1-thiomannosyl ligands, functionalized with an azide group, to liposomes containing a terminal alkyne-functionalized lipid anchor. Excellent coupling yields have been obtained in the presence of bathophenanthroline disulfonate, a water soluble copper-ion chelator, acting as a catalyst. No vesicle leakage is triggered by this conjugation reaction and the coupled mannose ligands are exposed at the surface of the liposomes. The major limitation of Cu(I)-catalyzed click reactions is that this conjugation is restricted to liposomes made of saturated (phospho)lipids. To circumvent that constraint, an example of alternative copper-free azide-alkyne click reaction has been developed. Molecular tools and results are presented here.

  11. Engineering Remotely Triggered Liposomes to Target Triple Negative Breast Cancer (United States)

    Sneider, Alexandra; Jadia, Rahul; Piel, Brandon; VanDyke, Derek; Tsiros, Christopher; Rai, Prakash


    Triple Negative Breast Cancer (TNBC) continues to present a challenge in the clinic, as there is still no approved targeted therapy. TNBC is the worst sub-type of breast cancer in terms of prognosis and exhibits a deficiency in estrogen, progesterone, and human epidermal growth factor 2 (HER2) receptors. One possible option for the treatment of TNBC is chemotherapy. The issue with many chemotherapy drugs is that their effectiveness is diminished due to poor water solubility, and the method of administration directly or with a co-solvent intravenously can lead to an increase in toxicity. The issues of drug solubility can be avoided by using liposomes as a drug delivery carrier. Liposomes are engineered, biological nanoconstructs that possess the ability to encapsulate both hydrophobic and hydrophilic drugs and have been clinically approved to treat cancer. Specific targeting of cancer cell receptors through the use of ligands conjugated to the surface of drug-loaded liposomes could lessen damage to normal, healthy tissue. This study focuses on polyethylene glycol (PEG)-coated, folate conjugated, benzoporphyrin derivative (BPD)-loaded liposomes for treatment via photodynamic therapy (PDT). The folate receptor is over expressed on TNBC cells so these liposomes are targeted for greater uptake into cancer cells. PDT involves remotely irradiating light at 690 nm to trigger BPD, a hydrophobic photosensitive drug, to form reactive oxygen species that cause tumor cell death. BPD also displays a fluorescence signal when excited by light making it possible to image the fluorescence prior to PDT and for theranostics. In this study, free BPD, non-targeted and folate-targeted PEGylated BPD-loaded liposomes were introduced to a metastatic breast cancer cell line (MDA-MB-231) in vitro. The liposomes were reproducibly synthesized and characterized for size, polydispersity index (PDI), zeta potential, stability, and BPD release kinetics. Folate competition tests, fluorescence

  12. Fluorescent temporin B derivative and its binding to liposomes. (United States)

    Sood, Rohit; Domanov, Yegor; Kinnunen, Paavo K J


    Temporins are short (10-13 amino acids) and linear antimicrobial peptides first isolated from the skin of the European red frog, Rana temporaria, and are effective against Gram-positive bacteria and Candida albicans. Similarly to other antimicrobial peptides, the association of temporins to lipid membranes has been concluded to underlie their antimicrobial effects. Accordingly, a detailed understanding of their interactions with phospholipids is needed. We conjugated a fluorophore (Texas Red) to a Cys containing derivative of temporin B (temB) and investigated its binding to liposomes by fluorescence spectroscopy. Circular dichroic spectra for the Cys-mutant recorded in the absence and in the presence of phospholipids were essentially similar to those for temB. A blue shift in the emission spectra and diminished quenching by ferrocyanide (FCN) of Texas Red labeled temporin B (TRC-temB) were seen in the presence of liposomes. Both of these changes can be attributed to the insertion of the Texas Red into the hydrophobic region of the bilayer. Resonance energy transfer, steady state anisotropy, and fluorescence lifetimes further demonstrate the interaction of TRC-temB with liposomes to be enhanced by negatively charged phospholipids. Instead, cholesterol attenuates the association of TRC-temB with membranes. The interactions between TRC-temB and liposomes of varying negative surface charge are driven by electrostatics as well as hydrophobicity. Similarly to native temporin B also TRC-temB forms amyloid type fibers in the presence of negatively charged liposomes. This property is likely to relate to the cytotoxic activity of this peptide.


    Directory of Open Access Journals (Sweden)

    Mr. Jatin B. Trivedi


    Full Text Available Targeting drug molecules to brain is one of the most challenging research areas in pharmaceuticalsciences. Drugs that are effective against diseases in the CNS and reach the brain via the bloodcompartment must pass the BBB. The blood-brain barrier (BBB represents an insurmountable obstaclefor a large number of drugs, including antibiotics, anti-neoplastic agents, and a variety of central nervoussystem (CNS-active drugs. Therefore, various strategies have been proposed to improve the delivery ofdifferent drugs to this tissue which includes liposomes, colloidal drug carriers, micelles, chimericpeptide technology, intranasal and olfactory route of administration and nano technology. The discoveryof liposome or lipid vesicle emerged from self forming enclosed lipid bi-layer upon hydration; liposomedrug delivery systems have played a significant role in formulation of potent drug to improvetherapeutics Liposomes have been investigated as carriers of various pharmacologically active agentssuch as antineoplastic, antimicrobial drugs, chelating agents, steroids, vaccines, and genetic materials.Liposomes provide an efficient drug delivery system because they can alter the pharmacokinetics andpharmacodynamics of the entrapped drugs. Liposomes have been widely used for brain delivery in vivo.Nowadays, the nasal route for systemic drug delivery has gained great interest. It provides severaladvantages over other routes of drug administrations, which includes rapid absorption, avoids intestinaland hepatic presystemic disposition and high potential for drug transfer to the CSF. Moreover, the nasalroute is a potential alternative route for systemic availability of drugs restricted to intravenousadministration, viz. peptide and protein drugs and vaccines. As well, intranasal route has also beensuccessfully exploited for bypassing the blood brain barrier [BBB] and subsequently delivering drugmolecules to central nervous system [CNS].

  14. Nuclisome: a novel concept for radionuclide therapy using targeting liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Fondell, Amelie; Carlsson, Joergen [Uppsala University, Department of Oncology, Radiology, and Clinical Immunology, Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Edwards, Katarina; Ickenstein, Ludger M. [Uppsala University, Department of Physical and Analytical Chemistry, Box 579, Uppsala (Sweden); Sjoeberg, Stefan [Uppsala University, Department of Biochemistry and Organic Chemistry, Box 599, Uppsala (Sweden); Gedda, Lars [Uppsala University, Department of Oncology, Radiology, and Clinical Immunology, Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden)


    For the treatment of cancer, the therapeutic potential of short-range, low-energy Auger-electron emitters, such as {sup 125}I, is getting progressively wider recognition. The potency of Auger-electron emitters is strongly dependent on their location in close vicinity to DNA. We have developed a new two-step targeting strategy to transport {sup 125}I into cancer-cell nuclei using PEG-stabilized tumour-cell targeting liposomes named ''Nuclisome-particles''. In the present study, epidermal growth factor (EGF) was used as a tumour-cell-specific agent to target the EGF-receptor (EGFR) and the liposomes were loaded with {sup 125}I-Comp1, a recently synthesized daunorubicin derivative. As analysed with cryo-TEM, the derivative precipitates inside liposomes at a drug-to-lipid molar ratio of 0.05:1. Receptor-specific uptake in cultured U-343MGaCl2:6 tumour cells of EGFR-targeting liposomes increased with time while non-specific and receptor-blocked uptake remained low. Nuclisome-particles were able to target single U-343MGaCl2:6 cells circulating in human blood during 4 h, with low uptake in white blood cells, as demonstrated in an ex vivo system using a Chandler loop. Autoradiography of targeted cells indicates that the grains from the radiolabelled drug are mainly co-localized with the cell nuclei. The successful targeting of the nucleus is shown to provide high-potency cell killing of cultured U-343MGaCl2:6 cells. At the concentration used, Nuclisome-particles were up to five orders of magnitude more effective in cell killing than EGFR-targeting liposomes loaded with doxorubicin. The results thus provide encouraging evidence that our two-step targeting strategy for tumour cell DNA has the potential to become an effective therapy against metastasizing cancer cells in the bloodstream. (orig.)

  15. Parenteral emulsions and liposomes to treat drug overdose. (United States)

    Damitz, Robert; Chauhan, Anuj


    Drug overdoses from both pharmaceutical and recreational drugs are a major public health concern. Although some overdoses may be treated with specific antidotes, the most common treatment involves providing supportive care to allow the body to metabolize and excrete the toxicant. In many cases, supportive care is limiting, ineffective, and expensive. There is a clear medical need to improve the effectiveness of detoxification, in particular by developing more specific therapies or antidotes for these overdoses. Intravenous lipid emulsions (ILEs) have been investigated as a potential treatment for overdoses of local anesthetics and other hydrophobic drugs. While ILE therapy has been successful in several cases, its use beyond local anesthetic systemic toxicity is controversial and its mechanism of detoxification remains a subject of debate. ILEs were not originally developed to treat overdose, but clarifying the mechanisms of detoxification observed with ILE may allow us to design more effective future treatments. Liposomes are highly biocompatible and versatile formulations, thus it was a natural step to explore their use for drug overdose therapy as well. Several researchers have designed liposomes using a variety of approaches including surface charge, pH gradients, and inclusion of enzymes in the liposome core to optimize the formulations for detoxification of a specific drug or toxicant. The in vitro results for drug sequestration by liposomes are very promising and animal trials have in some cases shown comparable performance to ILE at reduced lipid dosing. This narrative review summarizes the current status and advances in the use of emulsions and liposomes for detoxification and also suggests several areas in which studies are needed for developing future therapies.

  16. Cryogenic transmission electron microscopy of recombinant tuberculosis vaccine antigen with anionic liposomes reveals formation of flattened liposomes

    Directory of Open Access Journals (Sweden)

    Fox CB


    Full Text Available Christopher B Fox,1 Sean K Mulligan,2 Joyce Sung,2 Quinton M Dowling,1 H W Millie Fung,1 Thomas S Vedvick,1 Rhea N Coler1 1Infectious Disease Research Institute, Seattle, WA, USA; 2NanoImaging Services, La Jolla, CA, USA Abstract: Development of lipid-based adjuvant formulations to enhance the immunogenicity of recombinant vaccine antigens is a focus of modern vaccine research. Characterizing interactions between vaccine antigens and formulation excipients is important for establishing compatibility between the different components and optimizing vaccine stability and potency. Cryogenic transmission electron microscopy (TEM is a highly informative analytical technique that may elucidate various aspects of protein- and lipid-based structures, including morphology, size, shape, and phase structure, while avoiding artifacts associated with staining-based TEM. In this work, cryogenic TEM is employed to characterize a recombinant tuberculosis vaccine antigen, an anionic liposome formulation, and antigen–liposome interactions. By performing three-dimensional tomographic reconstruction analysis, the formation of a population of protein-containing flattened liposomes, not present in the control samples, was detected. It is shown that cryogenic TEM provides unique information regarding antigen–liposome interactions not detectable by light-scattering-based methods. Employing a suite of complementary analytical techniques is important to fully characterize interactions between vaccine components. Keywords: vaccine adjuvant; cryo-TEM; antigen-adjuvant interactions; vaccine physical characterization; vaccine formulation morphology; 3D tomographic reconstruction

  17. Cryogenic transmission electron microscopy of recombinant tuberculosis vaccine antigen with anionic liposomes reveals formation of flattened liposomes. (United States)

    Fox, Christopher B; Mulligan, Sean K; Sung, Joyce; Dowling, Quinton M; Fung, H W Millie; Vedvick, Thomas S; Coler, Rhea N


    Development of lipid-based adjuvant formulations to enhance the immunogenicity of recombinant vaccine antigens is a focus of modern vaccine research. Characterizing interactions between vaccine antigens and formulation excipients is important for establishing compatibility between the different components and optimizing vaccine stability and potency. Cryogenic transmission electron microscopy (TEM) is a highly informative analytical technique that may elucidate various aspects of protein- and lipid-based structures, including morphology, size, shape, and phase structure, while avoiding artifacts associated with staining-based TEM. In this work, cryogenic TEM is employed to characterize a recombinant tuberculosis vaccine antigen, an anionic liposome formulation, and antigen-liposome interactions. By performing three-dimensional tomographic reconstruction analysis, the formation of a population of protein-containing flattened liposomes, not present in the control samples, was detected. It is shown that cryogenic TEM provides unique information regarding antigen-liposome interactions not detectable by light-scattering-based methods. Employing a suite of complementary analytical techniques is important to fully characterize interactions between vaccine components.

  18. Cationic liposomes containing antioxidants reduces pulmonary injury in experimental model of sepsis: Liposomes antioxidants reduces pulmonary damage. (United States)

    Galvão, Andre Martins; Galvão, Júlia Siqueira; Pereira, Marcela Araújo; Cadena, Pabyton Gonçalves; Magalhães, Nereide Stella Santos; Fink, James B; de Andrade, Armele Dornelas; Castro, Celia Maria Machado Barbosa de; de Sousa Maia, Maria Bernadete


    The intracellular redox state of alveolar cells is a determining factor for tolerance to oxidative and pro-inflammatory stresses. This study investigated the effects of intratracheal co-administration of antioxidants encapsulated in liposomes on the lungs of rats subjected to sepsis. For this, male rats subjected to sepsis induced by lipopolysaccharide from Escherichia coli or placebo operation were treated (intratracheally) with antibiotic, 0.9% saline and antioxidants encapsulated or non-encapsulated in liposomes. Experimental model of sepsis by cecal ligation and puncture (CLP) was performed in order to expose the cecum. The cecum was then gently squeezed to extrude a small amount of feces from the perforation site. As an index of oxidative damage, superoxide anions, lipid peroxidation, protein carbonyls, catalase activity, nitrates/nitrites, cell viability and mortality rate were measured. Infected animals treated with antibiotic plus antioxidants encapsulated in liposomes showed reduced levels of superoxide anion (54% or 7.650±1.263 nmol/min/mg protein), lipid peroxidation (33% or 0.117±0.041 nmol/mg protein), protein carbonyl (57% or 0.039 ± 0.022 nmol/mg protein) and mortality rate (3.3%), p value <0.001. This treatment also reduced the level of nitrite/nitrate and increased cell viability (90.7%) of alveolar macrophages. Taken togheter, theses results support that cationic liposomes containing antioxidants should be explored as coadjuvants in the treatment of pulmonary oxidative damage.

  19. A Liposomal Formulation Able to Incorporate a High Content of Paclitaxel and Exert Promising Anticancer Effect

    Directory of Open Access Journals (Sweden)

    Pei Kan


    Full Text Available A liposome formulation for paclitaxel was developed in this study. The liposomes, composed of naturally unsaturated and hydrogenated phosphatidylcholines, with significant phase transition temperature difference, were prepared and characterized. The liposomes exhibited a high content of paclitaxel, which was incorporated within the segregated microdomains coexisting on phospholipid bilayer of liposomes. As much as 15% paclitaxel to phospholipid molar ratio were attained without precipitates observed during preparation. In addition, the liposomes remained stable in liquid form at 4∘C for at least 6 months. The special composition of liposomal membrane which could reduce paclitaxel aggregation could account for such a capacity and stability. The cytotoxicity of prepared paclitaxel liposomes on the colon cancer C-26 cell culture was comparable to Taxol. Acute toxicity test revealed that LD50 for intravenous bolus injection in mice exceeded by 40 mg/kg. In antitumor efficacy study, the prepared liposomal paclitaxel demonstrated the increase in the efficacy against human cancer in animal model. Taken together, the novel formulated liposomes can incorporate high content of paclitaxel, remaining stable for long-term storage. These animal data also demonstrate that the liposomal paclitaxel is promising for further clinical use.

  20. Macrophage depletion by clodronate liposome attenuates muscle injury and inflammation following exhaustive exercise

    Directory of Open Access Journals (Sweden)

    Noriaki Kawanishi


    Full Text Available Exhaustive exercise promotes muscle injury, including myofiber lesions; however, its exact mechanism has not yet been elucidated. In this study, we tested the hypothesis that macrophage depletion by pretreatment with clodronate liposomes alters muscle injury and inflammation following exhaustive exercise. Male C57BL/6J mice were divided into four groups: rest plus control liposome (n=8, rest plus clodronate liposome (n=8, exhaustive exercise plus control liposome (n=8, and exhaustive exercise plus clodronate liposome (n=8. Mice were treated with clodronate liposome or control liposome for 48 h before undergoing exhaustive exercise on a treadmill. Twenty-four hours after exhaustive exercise, the gastrocnemius muscles were removed for histological and PCR analyses. Exhaustive exercise increased the number of macrophages in the muscle; however, clodronate liposome treatment reduced this infiltration. Although exhaustive exercise resulted in an increase in injured myofibers, clodronate liposome treatment following exhaustive exercise reduced the injured myofibers. Clodronate liposome treatment also decreased the mRNA expression levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6 in the skeletal muscle after exhaustive exercise. These results suggest that macrophages play a critical role in increasing muscle injury by regulating inflammation.

  1. An evaluation of anti-tumor effect and toxicity of PEGylated ursolic acid liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qianqian; Zhao, Tingting; Liu, Yanping; Xing, Shanshan; Li, Lei; Gao, Dawei, E-mail: [Yanshan University, Applying Chemistry Key Lab of Hebei Province, Department of Bioengineer (China)


    Therapy of solid tumors mediated by nano-drug delivery has attracted considerable interest. In our previous study, ursolic acid (UA) was successfully encapsulated into PEGylated liposomes. The study aimed to evaluate the tumor inhibition effect and cytotoxicity of the PEGylated UA liposomes by U14 cervical carcinoma-bearing mice. The liposomes were spherical particles with mean particle diameters of 127.2 nm. The tumor inhibition rate of PEGylated UA liposomes was 53.60 % on U14 cervical carcinoma-bearing mice, which was greater than those of the UA solution (18.25 %) and traditional UA liposome groups (40.75 %). The tumor cells apoptosis rate of PEGylated UA liposomes was 25.81 %, which was significantly higher than that of the traditional UA liposomes (13.37 %). Moreover, the kidney and liver did not emerge the pathological changes in UA therapeutic mice by histopathological analysis, while there were significant differences on tumor tissues among three UA formulation groups. The PEGylated UA liposomes exhibited higher anti-tumor activity and lower cytotoxicity, and the main reason was that the coating PEG layer improved UA liposome properties, such as enhancing the stability of liposomes, promoting the effect of slow release, and prolonging the time of blood circulation. This may shed light on the development of PEGylated nano-vehicles.

  2. Superresolution and Fluorescence Dynamics Evidence Reveal That Intact Liposomes Do Not Cross the Human Skin Barrier.

    Directory of Open Access Journals (Sweden)

    Jes Dreier

    Full Text Available In this study we use the combination of super resolution optical microscopy and raster image correlation spectroscopy (RICS to study the mechanism of action of liposomes as transdermal drug delivery systems in human skin. Two different compositions of liposomes were applied to newly excised human skin, a POPC liposome and a more flexible liposome containing the surfactant sodium cholate. Stimulated emission depletion microscopy (STED images of intact skin and cryo-sections of skin treated with labeled liposomes were recorded displaying an optical resolution low enough to resolve the 100 nm liposomes in the skin. The images revealed that virtually none of the liposomes remained intact beneath the skin surface. RICS two color cross correlation diffusion measurements of double labeled liposomes confirmed these observations. Our results suggest that the liposomes do not act as carriers that transport their cargo directly through the skin barrier, but mainly burst and fuse with the outer lipid layers of the stratum corneum. It was also found that the flexible liposomes showed a greater delivery of the fluorophore into the stratum corneum, indicating that they functioned as chemical permeability enhancers.

  3. Antibiotic delivery by liposomes from prokaryotic microorganisms: Similia cum similis works better. (United States)

    Colzi, Ilaria; Troyan, Anna N; Perito, Brunella; Casalone, Enrico; Romoli, Riccardo; Pieraccini, Giuseppe; Škalko-Basnet, Nataša; Adessi, Alessandra; Rossi, Federico; Gonnelli, Cristina; Ristori, Sandra


    To date the effectiveness of antibiotics is undermined by microbial resistance, threatening public health worldwide. Enhancing the efficacy of the current antibiotic arsenal is an alternative strategy. The administration of antimicrobials encapsulated in nanocarriers, such as liposomes, is considered a viable option, though with some drawbacks related to limited affinity between conventional liposomes and bacterial membranes. Here we propose a novel "top-down" procedure to prepare unconventional liposomes from the membranes of prokaryotes (PD-liposomes). These vectors, being obtained from bacteria with limited growth requirements, also represent low-cost systems for scalable biotechnology production. In depth physico-chemical characterization, carried out with dynamic light scattering (DLS) and Small Angle X-ray Scattering (SAXS), indicated that PD-liposomes can be suitable for the employment as antibiotic vectors. Specifically, DLS showed that the mean diameter of loaded liposomes was ∼200-300nm, while SAXS showed that the structure was similar to conventional liposomes, thus allowing a direct comparison with more standard liposomal formulations. Compared to free penicillin G, PD-liposomes loaded with penicillin G showed minimal inhibitory concentrations against E. coli that were up to 16-times lower. Noteworthy, the extent of the bacterial growth inhibition was found to depend on the microorganisms from which liposomes were derived. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Influence of curcumin-loaded cationic liposome on anticancer activity for cervical cancer therapy. (United States)

    Saengkrit, Nattika; Saesoo, Somsak; Srinuanchai, Wanwisa; Phunpee, Sarunya; Ruktanonchai, Uracha Rungsardthong


    The delivery of curcumin has been explored in the form of liposomal nanoparticles to treat various cancer cells. Since curcumin is water insoluble and an effective delivery route is through encapsulation in liposomes, which were modified with three components of DDAB, cholesterol and non-ionic surfactant. The purpose of this study was to establish a critical role of DDAB in liposomes containing curcumin at cellular response against two types of cell lines (HeLa and SiHa). Here, we demonstrate that DDAB is a potent inducer of cell uptake and cell death in both cell lines. The enhanced cell uptake was found on DDAB-containing liposome, but not on DDAB-free liposome. However, the cytotoxicity of DDAB-containing liposomes was high and needs to be optimized. The cytotoxicity of liposomal curcumin was more pronounced than free curcumin in both cells, suggesting the benefits of using nanocarrier. In addition, the anticancer efficiency and apoptosis effect of the liposomal curcumin formulations with DDAB was higher than those of DDAB-free liposomes. Therefore curcumin loaded liposomes indicate significant potential as delivery vehicles for the treatment of cervical cancers.

  5. Polymer coated liposomes for dental drug delivery--interactions with parotid saliva and dental enamel. (United States)

    Nguyen, S; Hiorth, M; Rykke, M; Smistad, G


    The interactions between pectin coated liposomes and parotid saliva and dental enamel were studied to investigate their potential to mimic the protective biofilm formed naturally on tooth surfaces. Different pectin coated liposomes with respect to pectin type (LM-, HM- and AM-pectin) and concentration (0.05% and 0.2%) were prepared. Interactions between the pectin coated liposomes and parotid saliva were studied by turbidimetry and imaging by atomic force microscopy. The liposomes were adsorbed to hydroxyapatite (HA) and human dental enamel using phosphate buffer and parotid saliva as adsorption media. A continuous flow was imposed on the enamel surfaces for various time intervals to examine their retention on the dental enamel. The results were compared to uncoated, charged liposomes. No aggregation tendencies for the pectin coated liposomes and parotid saliva were revealed. This makes them promising as drug delivery systems to be used in the oral cavity. In phosphate buffer the adsorption to HA of pectin coated liposomes was significantly lower than the negative liposomes. The difference diminished in parotid saliva. Positive liposomes adsorbed better to the dental enamel than the pectin coated liposomes. However, when subjected to flow for 1h, no significant differences in the retention levels on the enamel were found between the formulations. For all formulations, more than 40% of the liposomes still remained on the enamel surfaces. At time point 20 min the retention of HM-pectin coated and positive liposomes were significantly higher. It was concluded that pectin coated liposomes can adsorb to HA as well as to the dental enamel. Their ability to retain on the enamel surfaces promotes the concept of using them as protective structures for the teeth.

  6. Firefly bioluminescent assay of ATP in the presence of ATP extractant by using liposomes. (United States)

    Kamidate, Tamio; Yanashita, Kenji; Tani, Hirofumi; Ishida, Akihiko; Notani, Mizuyo


    Liposomes containing phosphatidylcholine (PC) and cholesterol (Chol) were applied to the enhancer for firefly bioluminescence (BL) assay for ATP in the presence of cationic surfactants using as an extractant for the release of ATP from living cells. Benzalkonium chloride (BAC) was used as an ATP extractant. However, BAC seriously inhibited the activity of luciferase, thus resulting in the remarkable decrease in the sensitivity of the BL assay for ATP. On the other hand, we found that BAC was associated with liposomes to form cationic liposomes containing BAC. The association rate of BAC with liposomes was faster than that of BAC with luciferase. As a result, the inhibitory effect of BAC on luciferase was eliminated in the presence of liposomes. In addition, cationic liposomes thus formed enhanced BL emission. BL measurement conditions were optimized in terms of liposome charge type, liposome size, and total concentration of PC and Chol. ATP can be sensitively determined without dilution of analytical samples by using liposomes. The detection limit of ATP with and without liposomes was 100 amol and 25 fmol in aqueous ATP standard solutions containing 0.06% BAC, respectively. The method was applied to the determination of ATP in Escherichia coli extracts. The BL intensity was linear from 4 x 10(4) to 1 x 10(7) cells mL(-1) in the absence of liposomes. On the other hand, the BL intensity was linear from 4 x 10(3) to 4 x 10(6) cells mL(-1) in the presence of liposomes. The detection limit of ATP in E. coli extracts was improved by a factor of 10 via use of liposomes.

  7. Psoralen loaded liposomal nanocarriers for improved skin penetration and efficacy of topical PUVA in psoriasis. (United States)

    Doppalapudi, Sindhu; Jain, Anjali; Chopra, Dhiraj Kumar; Khan, Wahid


    Psoralen in combination with ultraviolet A radiation (PUVA) is an FDA recommended therapy for clinical application in the management of severe recalcitrant psoriasis. Psoralen acts by intercalation of DNA and upon exposure to UV-A, it forms monoadducts which in turn induce apoptosis. Poor skin deposition, weak percutaneous permeability of psoralen and adverse effects of severe burning, blisters, pigmentation associated with conventional topical psoralen vehicles hinders the therapeutic efficacy and safety of topical PUVA. The aim of the present study is to formulate psoralen loaded liposomal nanocarriers for enhanced skin penetration, safety and efficacy of topical PUVA in psoriasis. Two different liposomal compositions i.e., cationic liposomes composed of DC-Chol, cholesterol and anionic liposomes composed of egg lecithin, cholesterol, tetramyristoyl cardiolipin were prepared for the topical delivery of psoralen. Liposomal carriers were characterized with respect to size, zeta potential, entrapment efficiency, stability, in vitro drug release and in vivo studies. Both liposomes were prepared with particle size of nearly 100nm. Zeta potential and entrapment efficiency of cationic liposomes were +25.8mV, 75.12% and anionic liposomes were -28.5mV, 60.08% respectively. Liposomal dermal distribution demonstrated higher penetration of both liposomal carriers over solution. Similarly, skin permeation study indicated 5 fold increase in permeation of psoralen with liposomal carriers. Topical application of psoralen liposomal gels on imiquimod induced psoriatic plaque model reduced the symptoms of psoriasis and levels of key psoriatic cytokines such as tumor necrosis factor-α, IL-17 and IL-22. In conclusion, the developed liposomal carriers of psoralen were found to be promising and can find application for optimal safety and efficacy of topical PUVA in psoriasis. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Positive psychology and ideas of cultural-historical school of L.S. Vygotsky

    Directory of Open Access Journals (Sweden)

    Vasilev V.K.,


    Full Text Available In the article was carried out a comparative analysis between two distinctive psychology schools: the cultural-historical psychology of L.V. Vygotsky and the positive psychological school. Distinct are a number of significant similarities between their basic ideas that are valuable both for the development of human knowledge and for public practice. The authors have outlined and systematized the leading personal and intellectual qualities of the famous psychologists who have created the most promising theories in the psychological science. The category is highlighted as well as a small group of visionary psychologists who have identified the most important problems of man and psychology and have offered the best quality solutions to these problems. These are W. James, S. Freud, L. Vygotsky, E. Eriksson and A. Maslow; We’ve noticed that Vygotsky alone meets all the criteria, as if the concept of insightful psychologists was modeled over his creative work and his personality.

  9. Personnel Test Battery and Scoring Procedures. Memorandum No. L.S. 15. (United States)

    Berson, Barry L.

    The purpose of this memo is to present tests that comprise the test battery used to select Navy personnel to train marine mammals, and to describe the scoring procedures of the tests. The test battery consists of: Biosystems General Information Test (BGIT), Personnel History Questionnaire (PHQ), Gordon Personal Inventory, Gordon Personal Profile,…

  10. An upper bound for the L-S category of Sp(n)

    CERN Document Server

    Hunziker, Markus


    We prove that the (normalized) Lusternik-Schnirelmann category of the symplectic group Sp(n) is less or equal to [(n+2)^2/4]-1. Our techniques are Lie theoretic and can easily be generalized to find upper bounds for the Lusternik-Schnirelmann category of any simply connected compact Lie group. We conjecture that our upper bounds are sharp.


    NARCIS (Netherlands)


    This paper reports on a novel immunonadjuvant activity of liposomes. An influenza subunit preparation, containing the isolated viral surface antigens, was incorporated in a liposomal formulation. Administration of this vaccine to mice via the intranasal (i.n.) route resulted in a stimulated serum


    NARCIS (Netherlands)



    This paper reports on a novel immunonadjuvant activity of liposomes. An influenza subunit preparation, containing the isolated viral surface antigens, was incorporated in a liposomal formulation. Administration of this vaccine to mice via the intranasal (i.n.) route resulted in a stimulated serum Ig

  13. Meta-analysis of clinical and preclinical studies comparing the anticancer efficacy of liposomal versus conventional non-liposomal doxorubicin. (United States)

    Petersen, Grant H; Alzghari, Saeed K; Chee, Wayne; Sankari, Sana S; La-Beck, Ninh M


    While liposome-mediated delivery of cytotoxic chemotherapy has been shown to significantly enhance drug tolerability in patients as compared to the conventional formulation, the fundamental question remains whether they also improve anticancer efficacy. Thus, we performed a systematic literature search for randomized clinical trials directly comparing efficacy of liposomal cytotoxic chemotherapy versus their equivalent conventional formulation. The search yielded 14 clinical trials (8 anthracycline, 4 cisplatin, 1 paclitaxel, 1 irinotecan) that meet inclusion criteria, with a total of 2589 patients. We found that efficacy in patients was not different between liposomal and conventional chemotherapy as assessed by objective response (odds ratio 1.03; 95% confidence interval [CI] 0.82-1.30), overall survival (hazard ratio [HR] 1.05; 95% CI 0.95-1.17), and progression free survival rates (HR 1.01; 95% CI, 0.92-1.11). Subgroup analyses of only the anthracycline trials also did not show any efficacy advantage for the liposomal formulation. Since pegylated liposomal doxorubicin (PLD) was the most prevalent formulation in these clinical trials, we also performed a meta-analysis of 11 preclinical studies comparing efficacy of PLD and conventional doxorubicin in tumor-bearing mice. In contrast with clinical results, animal studies showed significantly increased survival in mice treated with PLD compared to conventional doxorubicin (HR 0.39; 95% CI 0.27-0.56). We discuss the possible reasons why the pharmacological advantages of carrier-mediated chemotherapy did not translate into enhanced clinical efficacy including the role of the enhanced permeability and retention (EPR) effect and the tumor microenvironment, the optimal dosing regimen for carrier-mediated agents, and the lack of standardization in the conduct and reporting of preclinical studies evaluating anticancer efficacy of these agents. Our study shows that the full clinical potential of carrier-mediated drugs

  14. In situ SAXS experiment during DNA and liposome complexation

    Energy Technology Data Exchange (ETDEWEB)

    Gasperini, A.A.; Cavalcanti, L.P. [Laboratorio Nacional de Luz Sincrotron (LNLS), Campinas, SP (Brazil); Balbino, T.A.; Torre, L.G. de la [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Oliveira, C.L.P. [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil)


    Full text: Gene therapy is an exciting research area that allows the treatment of different diseases. Basically, an engineered DNA that codes a protein is the therapeutic drug that has to be delivered to the cell nucleus. After that, the DNA transfection process allows the protein production using the cell machinery. However, the efficient delivery needs DNA protection against nucleases and interstitial fluids. In this context, the use of cationic liposome/DNA complexes is a promising strategy for non-viral gene therapy. Liposomes are lipid systems that self-aggregate in bilayers and the use of cationic lipids allows the electrostatic complexation with DNA. In this work, we used SAXS technique to study the complexation kinetics between cationic liposomes and plasmid DNA and evaluate the liposome structural modifications in the presence of DNA. Liposomes were prepared according to [1] using as plasmid DNA vector model a modified version of pVAX1-GFP with luciferase as reporter gene [2]. The complexation was promoted in a SAXS sample holder containing a microchannel to get access to the compartment between two mica windows where the X-ray beam could cross through [3]. We obtained in situ complexation using such sample holder coupled to a fed-batch reactor through a peristaltic pump. The scattering curves were recorded each 30 seconds during the cycles. The DNA was added until a certain final ratio between surface charges previously determined. We studied the form and structure factor model for the liposome bilayer to fit the scattering curves [4]. Structural information such as the bilayer electronic density profiles, number of bilayers and fluidity were determined as a function of the complexation with DNA. These differences can reflect in singular in vitro and in vivo effects. [1] L. G. de la Torre et al. Colloids and Surfaces B: Biointerfaces, 73, 175 (2009) [2] A. R. Azzoni et al. The Journal of Gene Medicine, 9, 392 (2007) [3] L. P. Cavalcanti et al. Review of

  15. Liposome functionalization with copper-free "click chemistry". (United States)

    Oude Blenke, Erik; Klaasse, Gruson; Merten, Hannes; Plückthun, Andreas; Mastrobattista, Enrico; Martin, Nathaniel I


    The modification of liposomal surfaces is of interest for many different applications and a variety of chemistries are available that makes this possible. A major disadvantage of commonly used coupling chemistries (e.g. maleimide-thiol coupling) is the limited control over the site of conjugation in cases where multiple reactive functionalities are present, leading to heterogeneous products and in some cases dysfunctional conjugates. Bioorthogonal coupling approaches such as the well-established copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction are attractive alternatives as the reaction kinetics are favorable and azide-containing reagents are widely available. In the work described here, we prepared lipids containing a reactive cyclooctyne group and, after incorporation into liposomes, demonstrated successful conjugation of both a small molecule dye (5'-TAMRA-azide) as well as a larger azide-containing model protein based upon a designed ankyrin repeat protein (azido-DARPin). By applying the strain-promoted azido-alkyne cycloaddition (SPAAC) the use of Cu(I) as a catalyst is avoided, an important advantage considering the known deleterious effects associated with copper in cell and protein studies. We demonstrate complete control over the number of ligands coupled per liposome when using a small molecule azide with conjugation occurring at a reasonable reaction rate. By comparison, the conjugation of a larger azide-modified protein occurs more slowly, however the number of protein ligands coupled was found to be sufficient for liposome targeting to cells. Importantly, these results provide a strong proof of concept for the site-specific conjugation of protein ligands to liposomal surfaces via SPAAC. Unlike conventional approaches, this strategy provides for the homogeneous coupling of proteins bearing a single site-specific azide modification and eliminates the chance of forming dysfunctional ligands on the liposome. Furthermore, the absence of

  16. Assembled liposomes of dual podophyllotoxin phospholipid: preparation, characterization and in vivo anticancer activity. (United States)

    Ling, Longbing; Yao, Chen; Du, Yawei; Ismail, Muhammad; He, Ruiyu; Hou, Yongpeng; Zhang, Ying; Li, Xinsong


    A novel amphiphilic prodrug dual podophyllotoxin (PPT) succinate glycerophosphorylcholine (Di-PPT-GPC) assembled liposomes was developed to improve efficiency of PPT. Di-PPT-GPC liposomes were prepared by thin film technique and characterized by dynamic light scattering and cryo-electron microscopy. In vitro release studies showed that Di-PPT-GPC liposomes could significantly release PPT in weakly acidic environment but had good stability under biological conditions. Methyl tetrazolium assay data revealed that the liposomes have comparable cytotoxicities to free PPT against MCF-7, HeLa and U87 cells. More importantly, in vivo antitumor evaluation indicated that Di-PPT-GPC liposomes exhibited favorable tumor growth inhibition without side effects. Di-PPT-GPC liposomes might have potential to promote the therapeutic effect of PPT for cancer therapy.

  17. Physicochemical characterization of liposomes after ultrasound exposure - mechanisms of drug release

    DEFF Research Database (Denmark)

    Evjen, Tove J; Hupfeld, Stefan; Barnert, Sabine


    Ultrasound is investigated as a novel drug delivery tool within cancer therapy. Non-thermal ultrasound treatment of solid tumours post i.v.-injection of drug-carrying liposomes may induce local drug release from the carrier followed by enhanced intracellular drug uptake. Recently, ultrasound......-mediated drug release of liposomes (sonosensitivity) was shown to strongly depend on liposome membrane composition. In the current study the ultrasound-mediated drug release mechanism of liposomes was investigated. The results showed that differences in ultrasound drug release kinetics obtained for different...... liposomal compositions were caused by distinctive release mechanisms of the carriers. Two types of liposomes composed of 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) and hydrogenated soy L-α-phosphatidylcholine (HSPC) as main lipids, respectively, were recently shown to vary in sonosensitivity...

  18. Liposomes containing alkylated methotrexate analogues for phospholipase A(2) mediated tumor targeted drug delivery

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars; Jensen, Simon Skøde


    cytotoxicity was incorporated into liposomes that were designed to be particularly Susceptible to a liposome degrading enzyme, secretory phospholipase A(2) (sPLA(2)), which is found in high concentrations in tumors of several different cancer types. Liposome incorporation was investigated by differential...... scanning calorimetry (DSC), and sPLA(2) hydrolysis was examined by fluorescence spectroscopy and high performance liquid chromatography (HPLC). The results showed that the methotrexate (MTX)-analogue could be incorporated into liposomes that were degradable by sPLA(2). However, the in vitro cytotoxicity...... of the MTX-liposomes against KATO III and HT-29 cancer cells was found to be independent of sPLA(2) hydrolysis, indicating that the alkylated MTX-analogue was available for cancer cell uptake even in the absence of liposome hydrolysis. Using a DSC based method for assessing the anchoring stability...

  19. Structure of liposome encapsulating proteins characterized by X-ray scattering and shell-modeling

    Energy Technology Data Exchange (ETDEWEB)

    Hirai, Mitsuhiro, E-mail:; Kimura, Ryota; Takeuchi, Kazuki; Hagiwara, Yoshihiko [Gunma University, 4-2 Aramaki, Maebashi, Gunma 371-8510 (Japan); Kawai-Hirai, Rika [Gunma University, 3-39-15 Shouwa, Maebashi 371-8512 (Japan); Ohta, Noboru [JASRI, 1-1-1 Kuoto, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan); Igarashi, Noriyuki; Shimuzu, Nobutaka [KEK-PF, 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan)


    Wide-angle X-ray scattering data using a third-generation synchrotron radiation source are presented. Lipid liposomes are promising drug delivery systems because they have superior curative effects owing to their high adaptability to a living body. Lipid liposomes encapsulating proteins were constructed and the structures examined using synchrotron radiation small- and wide-angle X-ray scattering (SR-SWAXS). The liposomes were prepared by a sequential combination of natural swelling, ultrasonic dispersion, freeze-throw, extrusion and spin-filtration. The liposomes were composed of acidic glycosphingolipid (ganglioside), cholesterol and phospholipids. By using shell-modeling methods, the asymmetric bilayer structure of the liposome and the encapsulation efficiency of proteins were determined. As well as other analytical techniques, SR-SWAXS and shell-modeling methods are shown to be a powerful tool for characterizing in situ structures of lipid liposomes as an important candidate of drug delivery systems.

  20. Micro and nano liposome vesicles containing curcumin for a drug delivery system (United States)

    Nguyen, Tuan Anh; Duoc Tang, Quan; Chanh Tin Doan, Duc; Chien Dang, Mau


    Micro and nano liposome vesicles were prepared using a lipid film hydration method and a sonication method. Phospholipid, cholesterol and curcumin were used to form micro and nano liposomes containing curcumin. The size, structure and properties of the liposomes were characterized by using optical microscopy, transmission electron microscopy, and UV-vis and Raman spectroscopy. It was found that the size of the liposomes was dependent on their composition and the preparation method. The hydration method created micro multilamellars, whereas nano unilamellars were formed using the sonication method. By adding cholesterol, the vesicles of the liposome could be stabilized and stored at 4 °C for up to 9 months. The liposome vesicles containing curcumin with good biocompatibility and biodegradability could be used for drug delivery applications.

  1. Inhibitory effect of liposome-entrapped lemongrass oil on the growth of Listeria monocytogenes in cheese. (United States)

    Cui, H Y; Wu, J; Lin, L


    Listeria monocytogenes infection in dairy products is of mounting public concern. To inhibit bacterial growth, we engineered stimuli-responsive liposomes containing lemongrass oil for this study. The controlled release of liposome-entrapped lemongrass oil is triggered by listerolysin O, secreted by L. monocytogenes. We investigated the antibiotic activities of lemongrass oil liposomes against L. monocytogenes in cheese. We also assessed their possible effects on the quality of the cheese. Liposomes containing lemongrass oil (5.0mg/mL) presented the optimal polydispersity index (0.246), zeta-potential (-58.9mV) and entrapment efficiency (25.7%). The liposomes displayed satisfactory antibiotic activity against L. monocytogenes in cheese over the storage period at 4°C. We observed no effects on the physical and sensory properties of the cheese after the liposome treatment. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  2. Salidroside liposome formulation enhances the activity of dendritic cells and immune responses. (United States)

    Zhao, Xiaojuan; Lu, Yu; Tao, Yang; Huang, Yee; Wang, Deyun; Hu, Yuanliang; Liu, Jiaguo; Wu, Yi; Yu, Yun; Liu, Cui


    Salidroside, the important composition, of Rhodiola rosea L. has been reported to have various pharmacological properties. Liposome is known to be effective as drug carriers and immune adjuvant. Therefore, the aim of this study is to investigate immunological adjuvant activity of salidroside liposome. Here we reported the preparation, the effect on DCs in vitro and the immune response in vivo. The immunological adjuvant activity of salidroside liposome formulation was compared with that of salidroside and liposome. The result showed that salidroside liposome formulation not only could promote the maturation of DCs, the stimulation of DCs on MLR proliferation and the antigen presenting ability, but also induced the sustained cellular immune and humoral immune response. Overall, the results showed that salidroside liposome formulation had the potential to act as effective sustained release vaccine delivery systems. © 2013.

  3. Evaluation of skin viability effect on ethosome and liposome-mediated psoralen delivery via cell uptake. (United States)

    Zhang, Yong-Tai; Shen, Li-Na; Wu, Zhong-Hua; Zhao, Ji-Hui; Feng, Nian-Ping


    This study investigated the effect of skin viability on its permeability to psoralen delivered by ethosomes, as compared with liposomes. With decreasing skin viability, the amount of liposome-delivered psoralen that penetrated through the skin increased, whereas skin deposition of psoralen from both ethosomes and liposomes reduced. Psoralen delivery to human-immortalized epidermal cells was more effective using liposomes, whereas delivery to human embryonic skin fibroblast cells was more effective when ethosomes were used. These findings agreed with those of in vivo studies showing that skin psoralen deposition from ethosomes and liposomes first increased and then plateaued overtime, which may indicate gradual saturation of intracellular drug delivery. It also suggested that the reduced deposition of ethosome- or liposome-delivered psoralen in skin with reduced viability may relate to reduced cellular uptake. This work indicated that the effects of skin viability should be taken into account when evaluating nanocarrier-mediated drug skin permeation.

  4. Fractal aggregates induced by liposome-liposome interaction in the presence of Ca2+. (United States)

    Sabín, J; Prieto, G; Ruso, J M; Sarmiento, F


    We present a study of the fractal dimension of clusters of large unilamellar vesicles (LUVs) formed by egg yolk phosphatidylcholine (EYPC), dimyristoylphosphocholine (DMPC) and dipalmitoylphosphocholine (DPPC) induced by Ca2+ . Fractal dimensions were calculated by application of two methods, measuring the angular dependency of the light scattered by the clusters and following the evolution of the cluster size. In all cases, the fractal dimensions fell in the range from 2.1 to 1.8, corresponding to two regimes: diffusion-limited cluster aggregation (DLCA) and reaction-limited cluster aggregation (RLCA). Whereas DMPC clusters showed a typical transition from the RLCA to the DLCA aggregation, EYPC exhibited an unusual behaviour, since the aggregation was limited for a higher concentration than the critical aggregation concentration. The behaviour of DPPC was intermediate, with a transition from the RLCA to the DLCA regimes with cluster sizes depending on Ca2+ concentration. Studies on the reversibility of the aggregates show that EYPC and DPPC clusters can be re-dispersed by dilution with water. DMPC does not present reversibility. Reversibility is evidence of the existence of secondary minima in the DLVO potential between two liposomes. To predict these secondary minima, a correction of the DLVO model was necessary taking into account a repulsive force of hydration.

  5. Undulating tubular liposomes through incorporation of a synthetic skin ceramide into phospholipid bilayers


    Xu, Peng; Tan, Grace; Zhou, Jia; He, Jibao; Lawson, Louise B.; McPherson, Gary L.; John, Vijay T.


    Non-spherical liposomes were prepared by doping L-α-phosphatidylcholine (PC) with ceramide VI (a skin lipid). Cryo-transmission electron microscopy shows the liposome shape changing from spherical to an undulating tubular morphology, when the amount ofceramide VI is increased. The formation of tubular liposomes is energetically favorableand is attributed to the association of ceramide VI with PC creating regions of lower curvature. Since ceramides are the major component of skin lipids inthe ...

  6. Undulating tubular liposomes through incorporation of a synthetic skin ceramide into phospholipid bilayers


    Xu, Peng; Tan, Grace; Zhou, Jia; He, Jibao; Lawson, Louise B.; McPherson, Gary L.; John, Vijay T.


    Non-spherical liposomes were prepared by doping L-α-phosphatidylcholine (PC) with ceramide VI (a skin lipid). Cryo-transmission electron microscopy shows the liposome shape changing from spherical to an undulating tubular morphology, when the amount ofceramide VI is increased. The formation of tubular liposomes is energetically favorableand is attributed to the association of ceramide VI with PC creating regions of lower curvature. Since ceramides are the major component of skin lipids inthe ...

  7. Epirubicin loaded with propylene glycol liposomes significantly overcomes multidrug resistance in breast cancer. (United States)

    Zhao, Ying-Zheng; Dai, Dan-Dan; Lu, Cui-Tao; Chen, Li-Juan; Lin, Min; Shen, Xiao-Tong; Li, Xiao-Kun; Zhang, Ming; Jiang, Xi; Jin, Rong-Rong; Li, Xing; Lv, Hai-Feng; Cai, Lu; Huang, Pin-Tong


    Multidrug resistance (MDR) is one of the major reasons for the failure of cancer chemotherapy. A newly reported liposome carrier, propylene glycol liposomes (EPI-PG-liposomes) were made to load epirubicin (EPI) which enhanced EPI absorption in MDR tumor cells to overcome the drug resistance. MDA-MB 435 and their mutant resistant (MDA-MB 435/ADR) cells were used to examine the cellular uptake and P-gp function in vitro for EPI-PG-liposomes by fluorescence microscopy and FCM, respectively. Mammary tumor model was also established to investigate the tumor growth inhibition and pharmacodynamics of EPI-PG-liposomes in vivo. Morphology evaluation showed that EPI-PG-liposomes had a homogeneous spherical shape with an average diameter of 182 nm. Based on cell viability assay, fluorescent microscopy examination, and EPI uptake assay, EPI-PG-liposomes exhibited an effective growth inhibition not only in MDA-MB-435 cells, but also in MDA-MB 435/ADR cells. EPI-PG-liposomes have high permeability not only on tumor cell membrane, but also on cell nucleus membrane. P-gp function assay showed that the anticancer action of EPI-PG-liposomes was not related to P-gp efflux pump, suggesting that PG-liposomes would not affect the normal physiological functions of membrane proteins. EPI-PG-liposomes also showed a better antitumor efficacy compared to EPI solution alone. With high entrapment efficiency, spherical morphology and effective inhibition on MDR cancer cells, EPI-PG-liposomes may represent a better chemotherapeutic vectors for cancer targeted therapy.

  8. Preparation, characterization, and in vitro release study of albendazole-encapsulated nanosize liposomes


    Panwar, Preety; Pandey, Bhumika; P C Lakhera; Singh, K. P.


    The purpose of the present study was to formulate effective and controlled release albendazole liposomal formulations. Albendazole, a hydrophobic drug used for the treatment of hydatid cysts, was encapsulated in nanosize liposomes. Rapid evaporation method was used for the preparation of albendazole-encapsulated conventional and PEGylated liposomes consisting of egg phosphatidylcholine (PC) and cholesterol (CH) in the molar ratios of (6:4) and PC:CH: polyethylene glycol (PEG) (5:4:1), respect...

  9. Transport and uptake effects of marine complex lipid liposomes in small intestinal epithelial cell models. (United States)

    Du, Lei; Yang, Yu-Hong; Xu, Jie; Wang, Yu-Ming; Xue, Chang-Hu; Kurihara, Hideyuki; Takahashi, Koretaro


    Nowadays, marine complex lipids, including starfish phospholipids (SFP) and cerebrosides (SFC) separated from Asterias amurensis as well as sea cucumber phospholipids (SCP) and cerebrosides (SCC) isolated from Cucumaria frondosa, have received much attention because of their potent biological activities. However, little information is known on the transport and uptake of these lipids in liposome forms in small intestinal cells. Therefore, this study was undertaken to investigate the effects of these complex lipid liposomes on transport and uptake in Caco-2 and M cell monolayer models. The results revealed that SFP and SCP contained 42% and 47.9% eicosapentaenoic acid (EPA), respectively. The average particle sizes of liposomes prepared in this study were from 169 to 189 nm. We found that the transport of the liposomes across the M cell monolayer model was much higher than the Caco-2 cell monolayer model. The liposomes consisting of SFP or SCP showed significantly higher transport and uptake than soy phospholipid (soy-PL) liposomes in both Caco-2 and M cell monolayer models. Our results also exhibited that treatment with 1 mM liposomes composed of SFP or SCP for 3 h tended to increase the EPA content in phospholipid fractions of both differentiated Caco-2 and M cells. Moreover, it was also found that the hybrid liposomes consisting of SFP/SFC/cholesterol (Chol) revealed higher transport and uptake across the M cell monolayer in comparison with other liposomes. Furthermore, treatment with SFP/SFC/Chol liposomes could notably decrease the trans-epithelial electrical resistance (TEER) values of Caco-2 and M cell monolayers. The present data also showed that the cell viability of differentiated Caco-2 and M cells was not affected after the treatment with marine complex lipids or soy-PL liposomes. Based on the data in this study, it was suggested that marine complex lipid liposomes exhibit prominent transport and uptake in small intestinal epithelial cell models.

  10. Protective effect of antigen delivery using monoolein-based liposomes in experimental hematogenously disseminated candidiasis


    Carneiro, Catarina; Correia, Alexandra; Lima, Tanea; Vilanova, Manuel; Pais, Célia; Gomes, Andreia; Real Oliveira, M. Elisabete C.D.; Sampaio, Paula


    We evaluated the potential of a liposomal antigen delivery system (ADS) containing Candida albicans cell wall surface proteins (CWSP) in mediating protection against systemic candidiasis. Treatment of bonemarrow- derived dendritic cells with CWSP-loaded dioctadecyldimethylammonium bromide:monoolein (DODAB:MO) liposomes enhanced and prolonged their activation comparatively to free antigen, indicating that liposome-entrapped CWSP were released more sustainable. Therefore, we immuniz...

  11. Effect of Cholesterol on the Properties of Spray-Dried Lysozyme-Loaded Liposomal Powders


    Charnvanich, Dusadee; Vardhanabhuti, Nontima; Kulvanich, Poj


    The influence of cholesterol (Chol) in the liposomal bilayer on the properties of inhalable protein-loaded liposomal powders prepared by spray-drying technique was investigated. Lysozyme (LSZ) was used as a model protein. Feed solution for spray drying was prepared by direct mixing of aqueous solution of LSZ with mannitol solution and empty liposome dispersions composed of hydrogenated phosphatidylcholine and Chol at various molar ratios. The spray-dried powders were characterized with respec...

  12. Antitumour activity of EPA-enriched phospholipids liposomes against S180 ascitic tumour-bearing mice


    Du, Lei; Yang, Yu-Hong; Wang, Yu-Ming; Xue, Chang-hu; Kurihara, Hideyuki; Takahashi, Koretaro


    The health benefits of eicosapentaenoic acid (EPA)-enriched phospholipids (PL) have witnessed a recent upsurge. In the present study, PL from starfish Asterias amurensis (SFP) and sea cucumber Cucumaria frondosa (SCP) were extracted and the liposomes were prepared. Both SFP and SCP liposomes showed antitumour effects in vitro and exhibited high transport and uptake effects in small intestinal epithelial cell models. The results also demonstrated that dietary SFP and SCP liposomes prolonged th...

  13. Elucidating the mechanisms of protein antigen adsorption to the CAF/NAF liposomal vaccine adjuvant systems

    DEFF Research Database (Denmark)

    Hamborg, Mette; Rose, Fabrice; Jorgensen, Lene


    adjuvant CAF01 composed of cationic dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB) or ii) the neutral adjuvant formulation NAF01, where DDA was replaced with zwitterionic distearoylphosphatidylcholine (DSPC). The effect of liposome charge, bilayer rigidity, isoelectric point...... interaction with the zwitterionic liposomes. In contrast, the net cationic lysozyme showed very little interaction with either types of liposome. Adsorption of α-lactalbumin altered its tertiary structure, affected lipid membrane packing below and above the phase transition temperature, and neutralized...

  14. Undulating tubular liposomes through incorporation of a synthetic skin ceramide into phospholipid bilayers. (United States)

    Xu, Peng; Tan, Grace; Zhou, Jia; He, Jibao; Lawson, Louise B; McPherson, Gary L; John, Vijay T


    Nonspherical liposomes were prepared by doping L-alpha-phosphatidylcholine (PC) with ceramide VI (a skin lipid). Cryo-transmission electron microscopy shows the liposome shape changing from spherical to an undulating tubular morphology, when the amount of ceramide VI is increased. The formation of tubular liposomes is energetically favorable and is attributed to the association of ceramide VI with PC creating regions of lower curvature. Since ceramides are the major component of skin lipids in the stratum corneum, tubular liposomes containing ceramide may potentially serve as self-enhanced nanocarriers for transdermal delivery.

  15. A novel liposome surface modification agent that prolongs blood circulation and retains surface ligand reactivity. (United States)

    Ishihara, Atsushi; Yamauchi, Masahiro; Tsuchiya, Tomoko; Mimura, Yukiteru; Tomoda, Yutaka; Katagiri, Ayato; Kamiya, Masaaki; Nemoto, Hisao; Suzawa, Toshiyuki; Yamasaki, Motoo


    Liposomes are recognized as potentially useful drug carriers but many problems preclude practical medical application. Liposomes bind with serum proteins (opsonization) and are captured by the reticuloendothelial system cells in the liver and spleen, which limits their ability to deliver drugs to other target sites. Modification of lipids with flexible, hydrophilic polymers such as poly(ethylene glycol) (PEG) to yield sterically stabilized liposomes is one approach to improve liposome blood circulation and tissue distribution properties. In this study, we examined liposomes prepared using lipids modified with a new branched oligoglycerol (BGL) moiety for steric stabilization. This novel BGL comprised 14 glycerol units (termed BGL014) connected with flexible ether linkages, resulting in a branched cascade-like structure that is highly expanded in aqueous solution. BGL014 was coupled to 1,2-distearoylphosphatidylethanolamine to yield BGL014-modified lipids. Incorporation of BGL014 into liposomes (BGL014L) resulted in long blood circulation times, despite a much thinner fixed aqueous layer thickness compared to PEG formulations. BGL014 produced a liposome surface coating that appears to function through steric inhibition of non-specific protein binding without strong interference of specific protein-binding reactions. Liposome structure and functionality was maintained following BGL014-modification, as the incorporation ratio of drug remained high. These results suggest that the BGL014 modification of liposomes is a promising approach to produce stable and long circulating drug carriers capable of selective binding to specific proteins.

  16. Modeling the Release Kinetics of Poorly Water-Soluble Drug Molecules from Liposomal Nanocarriers

    Directory of Open Access Journals (Sweden)

    Stephan Loew


    Full Text Available Liposomes are frequently used as pharmaceutical nanocarriers to deliver poorly water-soluble drugs such as temoporfin, cyclosporine A, amphotericin B, and paclitaxel to their target site. Optimal drug delivery depends on understanding the release kinetics of the drug molecules from the host liposomes during the journey to the target site and at the target site. Transfer of drugs in model systems consisting of donor liposomes and acceptor liposomes is known from experimental work to typically exhibit a first-order kinetics with a simple exponential behavior. In some cases, a fast component in the initial transfer is present, in other cases the transfer is sigmoidal. We present and analyze a theoretical model for the transfer that accounts for two physical mechanisms, collisions between liposomes and diffusion of the drug molecules through the aqueous phase. Starting with the detailed distribution of drug molecules among the individual liposomes, we specify the conditions that lead to an apparent first-order kinetic behavior. We also discuss possible implications on the transfer kinetics of (1 high drug loading of donor liposomes, (2 attractive interactions between drug molecules within the liposomes, and (3 slow transfer of drugs between the inner and outer leaflets of the liposomes.

  17. Wheat germ agglutinin modified liposomes for the photodynamic inactivation of bacteria. (United States)

    Yang, Kewei; Gitter, Burkhard; Rüger, Ronny; Albrecht, Volker; Wieland, Gerhard D; Fahr, Alfred


    Photodynamic inactivation (PDI) of bacteria is a promising approach for combating the increasing emergence of antibiotic resistance in pathogenic bacteria. To further improve the PDI efficiency on bacteria, a bacteria-targeting liposomal formulation was investigated. A generation II photosensitizer (temoporfin) was incorporated into liposomes, followed by conjugation with a specific lectin (wheat germ agglutinin, WGA) on the liposomal surface. WGA was successfully coupled to temoporfin-loaded liposomes using an activated phospholipid containing N-hydroxylsuccinimide residue. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were selected to evaluate the WGA modified liposomes in terms of bacteria targeted delivery and in vitro PDI test. Fluorescence microscopy revealed that temoporfin was delivered to both kinds of bacteria, while flow cytometry demonstrated that WGA- modified liposomes delivered more temoporfin to bacteria compared to nonmodified liposomes. Consequently, the WGA- modified liposomes eradicated all MRSA and significantly enhanced the PDI of P. aeruginosa. In conclusion, the WGA- modified liposomes are a promising formulation for bacteria targeted delivery of temoporfin and for improving the PDI efficiency of temoporfin on both Gram-positive and Gram-negative bacterial cells.

  18. Distribution and Inhibition of Liposomes on Staphylococcus aureus and Pseudomonas aeruginosa Biofilm.

    Directory of Open Access Journals (Sweden)

    Dong Dong

    Full Text Available Staphylococcus aureus and Pseudomonas aeruginosa are major pathogens in chronic rhinosinusitis (CRS and their biofilms have been associated with poorer postsurgical outcomes. This study investigated the distribution and anti-biofilm effect of cationic (+ and anionic (- phospholipid liposomes with different sizes (unilamellar and multilamellar vesicle, ULV and MLV respectively on S. aureus and P. aeruginosa biofilms.Specific biofilm models for S. aureus ATCC 25923 and P. aeruginosa ATCC 15692 were established. Liposomal distribution was determined by observing SYTO9 stained biofilm exposed to DiI labeled liposomes using confocal scanning laser microscopy, followed by quantitative image analysis. The anti-biofilm efficacy study was carried out by using the alamarBlue assay to test the relative viability of biofilm treated with various liposomes for 24 hours and five minutes.The smaller ULVs penetrated better than larger MLVs in both S. aureus and P. aeruginosa biofilm. Except that +ULV and -ULV displayed similar distribution in S. aureus biofilm, the cationic liposomes adhered better than their anionic counterparts. Biofilm growth was inhibited at 24-hour and five-minute exposure time, although the decrease of viability for P. aeruginosa biofilm after liposomal treatment did not reach statistical significance.The distribution and anti-biofilm effects of cationic and anionic liposomes of different sizes differed in S. aureus and P. aeruginosa biofilms. Reducing the liposome size and formulating liposomes as positively charged enhanced the penetration and inhibition of S. aureus and P. aeruginosa biofilms.

  19. Physical and Oxidative Stability of Uncoated and Chitosan-Coated Liposomes Containing Grape Seed Extract

    Directory of Open Access Journals (Sweden)

    Jochen Weiss


    Full Text Available Polyphenol-rich grape seed extract (0.1 w/w% was incorporated in liposomes (1 w/w% soy lecithin by high pressure homogenization (22,500 psi and coated with chitosan (0.1 w/w%. Primary liposomes and chitosan-coated secondary liposomes containing grape seed extract showed good physical stability during 98 days of storage. Most of the polyphenols were incorporated in the shell of the liposomes (85.4%, whereas only 7.6% of the polyphenols of grape seed extract were located in the interior of the liposomes. Coating with chitosan did not change the polyphenol content in the liposomes (86.6%. The uncoated liposomes without grape seed extract were highly prone to lipid oxidation. The cationic chitosan coating, however, improved the oxidative stability to some extent, due to its ability to repel pro-oxidant metals. Encapsulated grape seed extract showed high antioxidant activity in both primary and secondary liposomes, which may be attributed to its polyphenol content. In conclusion, the best chemical stability of liposomes can be achieved using a combination of grape seed extract and chitosan.

  20. Enhanced combination therapy effect on paclitaxel-resistant carcinoma by chloroquine co-delivery via liposomes

    Directory of Open Access Journals (Sweden)

    Gao MH


    Full Text Available Menghua Gao,1 Yuzhen Xu,1 Liyan Qiu2,3 1College of Pharmaceutical Sciences, 2Ministry of Education (MOE Key Laboratory of Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 3Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: A novel composite liposomal system co-encapsulating paclitaxel (PTX with chloroquine phosphate (CQ was designed for treating PTX-resistant carcinoma. It was confirmed that liposomal CQ can sensitize PTX by means of autophagy inhibition and competitively binding with multidrug-resistance transporters. Furthermore, according to the in vitro cytotoxicity and apoptosis assay, real-time observation of cellular uptake, and in vivo tissue distribution study, co-encapsulation of PTX and CQ in liposomes was validated as superior to the mixture of PTX liposome plus CQ liposome due to the simultaneous delivery and synergetic effect of the two drugs. Consequently, this composite liposome achieved significantly stronger anticancer efficacy in vivo than the PTX liposome plus CQ liposome mixture. This study helps to guide and enlighten ongoing and future clinical trials about the optimal administration modes for drug combination therapy. Keywords: paclitaxel, chloroquine, liposome, drug resistance, combination therapy

  1. Interaction of spermine with dimyristoyl-L-alpha-phosphatidyl-DL-glycerol multilamellar liposomes. (United States)

    Stevanato, R; Wisniewska, A; Momo, F


    Polycationic spermine interacts with the negative phosphate group of dimyristoylphosphatidylglycerol multilamellar liposomes, forming a positively charged shell around the vesicle surface. An association constant of (2.15+/-0.45) x 10(3) M(-1) between spermine and the phospholipid groups in liposomes has been evaluated by a new and rapid enzymatic method. ESR spectra show that the effects of this polycation on liposomes are substantially different from those of cations like Ca2+ and Mg2+ and confirm the ability of spermine to induce liposome aggregation and not fusion.

  2. Hemocompatibility of liposomes loaded with lipophilic prodrugs of methotrexate and melphalan in the lipid bilayer. (United States)

    Kuznetsova, Natalia R; Sevrin, Chantal; Lespineux, David; Bovin, Nicolai V; Vodovozova, Elena L; Mészáros, Tamás; Szebeni, Janos; Grandfils, Christian


    A panel of in vitro tests intended for evaluation of the nano-sized drug delivery systems' compliance with human blood was applied to liposomal formulations of anticancer lipophilic prodrugs incorporated into the lipid bilayer. Liposomes on the basis of natural phosphatidylcholine (PC) and phosphatidylinositol (PI), 8:1 (mol) were loaded with 10 mol% of either methotrexate or melphalan 1,2-dioleoylglyceride esters (MTX-DOG and Mlph-DOG respectively) and either decorated with 2 mol% of sialyl Lewis X/A (SiaLe(X/A)) tetrasaccharide ligand or not. Hemolysis rate, red blood cells and platelets integrity and size distribution, complement (C) activation, and coagulation cascade functioning were analyzed upon the material incubation with whole blood. Both formulations were negatively charged with the zeta potential value being higher in the case of MTX-DOG liposomes, which also were larger than Mlph-DOG liposomes and more prone to aggregation. Accordingly, in hemocompatibility tests Mlph-DOG liposomes did not provoke any undesirable effects, while MTX-DOG liposomes induced significant C activation and abnormal coagulation times in a concentration-dependent manner. Reactivity of the liposome surface was not affected by the presence of SiaLe(X/A) or PI. Decrease in liposome loading with MTX-DOG from 10 to 2.5% resulted in lower surface charge density, smaller liposome size and considerably reduced impact on C activation and coagulation cascades.

  3. Physical and oxidative stability of uncoated and chitosan-coated liposomes containing grape seed extract. (United States)

    Gibis, Monika; Rahn, Nina; Weiss, Jochen


    Polyphenol-rich grape seed extract (0.1 w/w%) was incorporated in liposomes (1 w/w% soy lecithin) by high pressure homogenization (22,500 psi) and coated with chitosan (0.1 w/w%). Primary liposomes and chitosan-coated secondary liposomes containing grape seed extract showed good physical stability during 98 days of storage. Most of the polyphenols were incorporated in the shell of the liposomes (85.4%), whereas only 7.6% of the polyphenols of grape seed extract were located in the interior of the liposomes. Coating with chitosan did not change the polyphenol content in the liposomes (86.6%). The uncoated liposomes without grape seed extract were highly prone to lipid oxidation. The cationic chitosan coating, however, improved the oxidative stability to some extent, due to its ability to repel pro-oxidant metals. Encapsulated grape seed extract showed high antioxidant activity in both primary and secondary liposomes, which may be attributed to its polyphenol content. In conclusion, the best chemical stability of liposomes can be achieved using a combination of grape seed extract and chitosan.

  4. Modulating effect of lipid bilayer-carotenoid interactions on the property of liposome encapsulation. (United States)

    Xia, Shuqin; Tan, Chen; Zhang, Yating; Abbas, Shabbar; Feng, Biao; Zhang, Xiaoming; Qin, Fang


    Liposomes have become an attractive alternative to encapsulate carotenoids to improve their solubility, stability and bioavailability. The interaction mechanism of carotenoid with lipid bilayer is one of the major concerns in improving the delivery efficiency of liposomes. In this study, the microstructure and carotenoid encapsulation efficiency of liposomes composed of native phospholipid (egg yolk phosphatidylcholine, EYPC) and nonionic surfactant Tween 80 were investigated by atomic force microscopy, dynamic light scattering, and Raman spectroscopy, respectively. Subsequently, the effects of carotenoid incorporation on the physical properties of liposomal membrane were performed by Raman spectroscopy, fluorescence polarization, and electron paramagnetic resonance. Results showed that the incorporation of carotenoids affected the liposomes morphology, size and size distribution to various extents. Analysis on the Raman characteristic peaks of carotenoids revealed that lutein exhibited the strongest incorporating ability into liposomes, followed by β-carotene, lycopene, and canthaxanthin. Furthermore, it was demonstrated that carotenoids modulated the dynamics, structure and hydrophobicity of liposomal membrane, highly depending on their molecular structures and incorporated concentration. These modulations were closely correlated with the stabilization of liposomes, including mediating particle aggregation and fusion. These findings should guide the rationale designing for liposomal encapsulation technology to efficiently deliver carotenoids in pharmaceutics, nutraceuticals and functional foods.

  5. An approach to minimize Pseudomembranous colitis caused by clindamycin through liposomal formulation

    Directory of Open Access Journals (Sweden)

    Ramana M


    Full Text Available Liposomal encapsulation is known to significantly improve the therapeutic index of a drug. In the present investigation liposomal formulations were chosen to transport clindamycin, which is considered as the most effective topical antibiotic for acne, into the skin layers. Liposomes with clindamycin phosphate were prepared using lipid film hydration method and the optimum ratio of the components was determined. The liposomes were characterized for their vesicle size, shape, encapsulation efficiency, % drug content and for in vitro skin permeation study. The results suggest that the average size of vesicles was found to be in range of 4.91-6.75 µm. Highest encapsulation efficiency (45.4% and in vitro skin permeation (62% was achieved with a formulation containing drug: lipid: cholesterol in the ratio of 1:1:1. Liposomal formulation of clindamycin phosphate with good skin permeation properties was incorporated into gel base and comparison of in vitro skin permeation was made with non liposomal marketed gel, both containing 1% clindamycin phosphate. Higher rate of drug release across the rat abdominal skin was found with liposomal gel (54% than non-liposomal marketed gel (48.7%. Biological study revealed that by encapsulating clindamycin phosphate into liposomes the occurrence of Pseudomembranous colitis could be reduced significantly in comparison to plain clindamycin phosphate.

  6. Effect of cholesterol on the interaction of the amphibian antimicrobial peptide DD K with liposomes. (United States)

    Verly, Rodrigo M; Rodrigues, Magali A; Daghastanli, Katia Regina P; Denadai, Angelo Márcio L; Cuccovia, Iolanda M; Bloch, Carlos; Frézard, Frédéric; Santoro, Marcelo M; Piló-Veloso, Dorila; Bemquerer, Marcelo P


    DD K is an antimicrobial peptide previously isolated from the skin of the amphibian Phyllomedusa distincta. The effect of cholesterol on synthetic DD K binding to egg lecithin liposomes was investigated by intrinsic fluorescence of tryptophan residue, measurements of kinetics of 5(6)-carboxyfluorescein (CF) leakage, dynamic light scattering and isothermal titration microcalorimetry. An 8 nm blue shift of tryptophan maximum emission fluorescence was observed when DD K was in the presence of lecithin liposomes compared to the value observed for liposomes containing 43 mol% cholesterol. The rate and the extent of CF release were also significantly reduced by the presence of cholesterol. Dynamic light scattering showed that lecithin liposome size increase from 115 to 140 nm when titrated with DD K but addition of cholesterol reduces the liposome size increments. Isothermal titration microcalorimetry studies showed that DD K binding both to liposomes containing cholesterol as to liposomes devoid of it is more entropically than enthalpically favored. Nevertheless, the peptide concentration necessary to furnish an adjustable titration curve is much higher for liposomes containing cholesterol at 43 mol% (2 mmol L(-1)) than in its absence (93 micromol L(-1)). Apparent binding constant values were 2160 and 10,000 L mol(-1), respectively. The whole data indicate that DD K binding to phosphatidylcholine liposomes is significantly affected by cholesterol, which contributes to explain the low hemolytic activity of the peptide.

  7. Effect of cholesterol on the properties of spray-dried lysozyme-loaded liposomal powders. (United States)

    Charnvanich, Dusadee; Vardhanabhuti, Nontima; Kulvanich, Poj


    The influence of cholesterol (Chol) in the liposomal bilayer on the properties of inhalable protein-loaded liposomal powders prepared by spray-drying technique was investigated. Lysozyme (LSZ) was used as a model protein. Feed solution for spray drying was prepared by direct mixing of aqueous solution of LSZ with mannitol solution and empty liposome dispersions composed of hydrogenated phosphatidylcholine and Chol at various molar ratios. The spray-dried powders were characterized with respect to morphology, thermal property, and crystallinity using scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction, respectively. Most formulations gave slightly aggregated, spherical particles, and percentage yields of the spray-dried powders decreased with increasing Chol content. Degree of particle aggregation depended on the powder composition. The powders spontaneously formed liposomes which efficiently entrapped LSZ after reconstitution with HEPES buffered saline (HBS) at 37 degrees C. Lysozyme entrapment efficiency and size distribution of the reconstituted liposomes were evaluated after the powders were reconstituted with HBS. Increasing Chol content resulted in a decrease in size of the reconstituted liposomes and an increase in entrapment efficiency of LSZ. These results correlated with thermal behaviors of the reconstituted liposomes. Biological activity of LSZ was not affected by the spray-drying process. It was also demonstrated that LSZ-loaded liposomal powders could be produced without the need to preload the LSZ into liposomes prior to spray-drying process.

  8. Optimization on Preparation Conditions of Salidroside Liposome and Its Immunological Activity on PCV-2 in Mice

    Directory of Open Access Journals (Sweden)

    Yibo Feng


    Full Text Available The aim of this study was to optimize the preparation conditions of salidroside liposome with high encapsulation efficiency (EE and to study the immunological enhancement activity of salidroside liposome as porcine circovirus type 2 virus (PCV-2 vaccine adjuvant. Response surface methodology (RSM was selected to optimize the conditions for the preparation of salidroside liposome using Design-Expert V8.0.6 software. Three kinds of salidroside liposome adjuvants were prepared to study their adjuvant activity. BALB/c mice were immunized with PCV-2 encapsulated in different kinds of salidroside liposome adjuvants. The PCV-2-specific IgG in immunized mice serum was determined with ELISA. The results showed that when the concentration of ammonium sulfate was 0.26 mol·L−1, ethanol volume 6.5 mL, temperature 43°C, ethanol injection rate 3 mL·min−1, and salidroside liposome could be prepared with high encapsulation efficiency of 94.527%. Salidroside liposome as adjuvant could rapidly induce the production of PCV-2-specific IgG and salidroside liposome I adjuvant proved to provide the best effect among the three kinds of salidroside liposome adjuvants.

  9. Modeling the Release Kinetics of Poorly Water-Soluble Drug Molecules from Liposomal Nanocarriers (United States)

    Loew, Stephan; Fahr, Alfred; May, Sylvio


    Liposomes are frequently used as pharmaceutical nanocarriers to deliver poorly water-soluble drugs such as temoporfin, cyclosporine A, amphotericin B, and paclitaxel to their target site. Optimal drug delivery depends on understanding the release kinetics of the drug molecules from the host liposomes during the journey to the target site and at the target site. Transfer of drugs in model systems consisting of donor liposomes and acceptor liposomes is known from experimental work to typically exhibit a first-order kinetics with a simple exponential behavior. In some cases, a fast component in the initial transfer is present, in other cases the transfer is sigmoidal. We present and analyze a theoretical model for the transfer that accounts for two physical mechanisms, collisions between liposomes and diffusion of the drug molecules through the aqueous phase. Starting with the detailed distribution of drug molecules among the individual liposomes, we specify the conditions that lead to an apparent first-order kinetic behavior. We also discuss possible implications on the transfer kinetics of (1) high drug loading of donor liposomes, (2) attractive interactions between drug molecules within the liposomes, and (3) slow transfer of drugs between the inner and outer leaflets of the liposomes. PMID:21773045

  10. In vitro delivery of curcumin with cholesterol-based cationic liposomes. (United States)

    Apiratikul, N; Penglong, T; Suksen, K; Svasti, S; Chairoungdua, A; Yingyongnarongkula, B


    A new cholesterol-based cationic lipid was synthesized; liposomes prepared on its basis were evaluated as drug delivery vehicles for curcumin. Free and liposome-encapsulated curcumin cytotoxicity against HeLa, A549, HepG2, K562 and 1301 cell lines was assessed. Liposomal curcumin with ED50 values ranging from 2.5-10 microM exhibited 2-8 times higher cytotoxicity than free curcumin. The synthetic cholesterol-based cationic lipid also enhanced cellular uptake of curcumin into tested cells. Cationic liposome alone showed low cytotoxicity at high doses with ED50 values of 90-210 microM.

  11. Measurements of liposome biomechanical properties by combining line optical tweezers and dielectrophoresis. (United States)

    Spyratou, Ellas; Cunaj, Efrosini; Tsigaridas, George; Mourelatou, Elena A; Demetzos, Costas; Serafetinides, Alexander A; Makropoulou, Mersini


    Abstract Liposomes are well-known cell simulators and are currently studied as drug delivery systems, for a targeted delivery of higher drug concentrations, in specific cells. Novel biophotonic techniques for manipulation and characterization of liposomes have been developed; among which are optical tweezers. In our work, we demonstrate a novel use of line optical tweezers to manipulate and cause liposome deformations. Optical forces induce tension on liposomes, which are stretched along the line optical trap. The method of dielectrophoresis, combined with optical tweezers, was used to measure the exerted optical forces. As a consequence, in the case of reversible liposome deformations, the value of the shear and bending moduli of liposomes was calculated. We anticipate that the selective manipulation of liposomes will help us toward a better understanding of the cellular-liposome interactions. Studying the biomechanical properties of liposomes will provide an insight into the mechanical behavior of individual living cells, which have recently been implicated in many aspects of human physiology and patho-physiology. The biomechanical properties of cells (i.e. deformability, stiffness and elasticity) can be useful biomarkers for various disease processes and changes of the cell state.


    Directory of Open Access Journals (Sweden)

    Suraj R. Wasankar*, Syed M. Faizi and Abhisek D. Deshmuk


    Full Text Available Aim: The aims of this study were to develop liposome enriched Dexibuprofen liposomal hydrogels for topical delivery, perform in vitro release studies and in vivo permeation studies through mice/rat skin, and evaluate the efficacy of liposomal gels against inflammation induced rats. The purpose was to provide the delivery of the topical drug at a sustained rate across intact skin to improve bioavailability and inflammation control for longer period from liposomal gels.Method: Phosphatidylcholine, Cholesterol and Dexibuprofen were dissolved in chloroform/methanol (2:1, v/v mixture and subsequently transferred into a pear-shaped flask connected to a Rotavapor (Büchi- type. Rotary evaporation method was used for the formulation of liposomes.Result: liposome prepared was evaluated for particle size measurement, percent drug entrapment, diffusion study, skin permeation study and in vivo study. F-7 batch found to be optimized batch having particle size 5.40 µm, % drug entrapment 61.70, % CDR 75.35 %. Hence F-7 batch further evaluated for skin permeation study, skin deposition study, in vivo study and stability study.Conclusion: The present study has been a satisfactory attempt to formulate and evaluate liposome of Dexibuprofen and liposomal gel with a providing sustained delivery of drug. From skin permeation study and in vivo study it was concluded that the prepared liposome of Dexibuprofen may prove to be potential candidate for safe and effective sustained drug delivery over an extended period of time which can reduce dosing frequency.

  13. Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice

    Institute of Scientific and Technical Information of China (English)

    Zheng-hong WU; Qi-neng PING; Yi WEI; Jia-ming LAI


    AIM: To evaluate the hypoglycemic efficacy of insulin liposomes coated by chitosan with different molecular weights and concentrations after oral administration in mice. METHODS: Insulin-liposomes were prepared by reversed-phase evaporation. Chitosan coating was carried out by incubation of the liposomal suspensions with the chitosan solution. The hypoglycemic efficacies of chitosan-coated insulin liposomes were investigated by monitoring the blood glucose level using the glucose oxidase method after oral administration to healthy mice. RESULTS:In all the insulin liposomes, the insulin liposomes coated by 0.2 % chitosan (M. 1000 kDa) showed a better hypoglycemic efficacy as compared with the other liposomes coated by chitosan. The minimum blood glucose level was 15.1%±6.0 % of the initial (n=6). The hypoglycemic efficacy lasted for 4 h after oral administration to mice.CONCLUSION: Chitosan-coated liposomes could reduce tryptic digestion on insulin, and enhance enteral absorption of insulin. The molecular weights and concentrations of chitosan had significant effects on hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration to healthy mice.

  14. Chiral DNA packaging in DNA-cationic liposome assemblies. (United States)

    Zuidam, N J; Barenholz, Y; Minsky, A


    Recent studies have indicated that the structural features of DNA-lipid assemblies, dictated by the lipid composition and cationic lipid-to-DNA ratio, critically affect the efficiency of these complexes in acting as vehicles for cellular delivery of genetic material. Using circular dichroism we find that upon binding DNA, positively-charged liposomes induce a secondary conformational transition of the DNA molecules from the native B form to the C motif. Liposomes composed of positively-charged and neutral 'helper' lipids, found to be particularly effective as transfecting agents, induce - in addition to secondary conformational changes - DNA condensation into a left-handed cholesteric-like phase. A structural model is presented according to which two distinct, yet inter-related modes of DNA packaging coexist within such assemblies. The results underline the notion that subtle changes in the components of a supramolecular assembly may substantially modulate the interplay of interactions which dictate its structure and functional properties.

  15. Multifunctional liposomes for enhanced anti-cancer therapy (United States)

    Falcao, Claudio Borges


    Macromolecular drugs have great promises for cancer treatment, such as the pro-apoptotic peptide D-(KLAKLAK)2 and the bcl-2 antisense oligodeoxynucleotide G3139. However, these macromolecules require efficient drug carriers, like liposomes, to deliver them inside cells. Also, if these macromolecules can be combined in a single liposome, the cancer cell killing will be greater than using just one. With this possibility in mind, cationic liposomes (CLs) were elaborated to encapsulate both macromolecules and deliver them inside cells. Later, surface modification of CLs was investigated through the addition of polyethylene glycol (PEG) to obtain long-circulating liposomes. CLs were prepared through charge alternation among D-(KLAKLAK)2 , G3139 and DOTAP. These liposomes were characterized with particle size and zeta-potential measurements, antisense entrapment and peptide loading efficiency. The in vitro effects of CL formulations were tested with B16(F10) cells through viability studies, uptake assay and detection of apoptosis. CL formulations were also applied in vivo in B16(F10) tumor-bearing mice through intratumoral injections, and tumor growth inhibition and detection of apoptosis were evaluated. Next, the mechanism of action of the CL formulations was investigated by Western blotting. Later, PEG was incorporated at increasing amounts to the liposomes to determine which concentration can better prevent interactions between PEG-cationic liposomes (PCL) and B16(F10) cells. Next, pH-cleavable PEG was prepared and then added to the liposomes in the same amount that PEG in PCL could decrease interaction with cells. Finally, cell viability studies were performed with CL, PCL and pH-sensitive PCL (pH-PCL) formulations after pre-incubation at pH 7.4 or at pH 5.0. Positively charged CL particles were obtained after encapsulation of negatively charged D-(KLAKLAK)2/G3139 complexes. In vitro , CLs containing D-(KLAKLAK)2/G3139 complexes could reduce B16(F10) cell viability

  16. Alleviating Thoracotomy Pain With Intercostal Liposomal Bupivacaine: A Case Report. (United States)

    Saby, Adam; Swaminathan, Kavitha; Pangarkar, Sanjog; Tribuzio, Bianca


    Thoracotomy pain is common after chest surgery and may result from injury to the lung pleura, intercostal muscles, costovertebral joint, or intercostal nerves. Inappropriately controlled postoperative pain can hinder recovery and increase the risk of complications such as infection, atelectasis, blood clots, and development of post-thoracotomy pain syndrome. A number of treatment options for acute pain are available, most of which require systemic medications or indwelling catheters that may be contraindicated in patients on anticoagulants. We present the case of a patient with post-thoracotomy pain that effectively was treated with an ultrasound-guided nerve block with liposomal bupivacaine. The patient experienced pain relief without adverse event. Liposomal bupivacaine may be considered a potential treatment option for patients with severe acute post-thoracotomy pain in whom other modalities have not worked or are contraindicated. N/A. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  17. Development of Liposomal Ciprofloxacin to Treat Lung Infections

    Directory of Open Access Journals (Sweden)

    David Cipolla


    Full Text Available Except for management of Pseudomonas aeruginosa (PA in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively. Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin® and Pulmaquin® that are in development by Aradigm Corporation are described here.

  18. Lateral Tension-Induced Penetration of Particles into a Liposome

    Directory of Open Access Journals (Sweden)

    Kazuki Shigyou


    Full Text Available It is important that we understand the mechanism of the penetration of particles into a living cell to achieve advances in bionanotechnology, such as for treatment, visualization within a cell, and genetic modification. Although there have been many studies on the application of functional particles to cells, the basic mechanism of penetration across a biological membrane is still poorly understood. Here we used a model membrane system to demonstrate that lateral membrane tension drives particle penetration across a lipid bilayer. After the application of osmotic pressure, fully wrapped particles on a liposome surface were found to enter the liposome. We discuss the mechanism of the tension-induced penetration in terms of narrow constriction of the membrane at the neck part. The present findings are expected to provide insight into the application of particles to biological systems.

  19. Recurrent Candida albicans Ventriculitis Treated with Intraventricular Liposomal Amphotericin B

    Directory of Open Access Journals (Sweden)

    Demet Toprak


    Full Text Available Central nervous system (CNS infection with Candida is rare but significant because of its high morbidity and mortality. When present, it is commonly seen among immunocompromised and hospitalized patients. Herein, we describe a case of a four-year-old boy with acute lymphoblastic leukemia (ALL who experienced recurrent Candida albicans meningitis. The patient was treated successfully with intravenous liposomal amphotericin B at first attack, but 25 days after discharge he was readmitted to hospital with symptoms of meningitis. Candida albicans was grown in CFS culture again and cranial magnetic resonance imaging (MRI showed ventriculitis. We administered liposomal amphotericin B both intravenously and intraventricularly and favorable result was achieved without any adverse effects. Intraventricular amphotericin B may be considered for the treatment of recurrent CNS Candida infections in addition to intravenous administration.

  20. Liposomal amphotericin B as a treatment for human leishmaniasis


    Balasegaram, Manica; Ritmeijer, Koert; Lima, Maria Angeles; Burza, Sakib; Ortiz Genovese, Gemma; Milani, Barbara; Gaspani, Sara; Potet, Julien; Chappuis, François


    Abstract INTRODUCTION: Leishmaniasis is a parasitic disease transmitted by phlebotomine sandflies. Between 700,000 and 1.2 million cases of cutaneous leishmaniasis and between 200,000 and 400,000 cases of visceral leishmaniasis (VL), which is fatal if left untreated, occur annually worldwide. Liposomal amphotericin B (LAMB), alone or in combination with other drugs, has been extensively studied as VL treatment, but data on routine field use are limited, and several challenges to patients' acc...

  1. [Liposome phospholipid substitution and lung function in surfactant deprived rats]. (United States)

    Obladen, M


    In vivo activity of an artificial surfactant was studied in surfactant depleted rats. After tenfold alveolar lavage, PaO2, tidal volume, and compliance of the respiratory system fell to one third of initial value. Substitution of large unilamellar vesicles containing 90% Dipalmitoylphosphatidylcholine and 10% unsaturated phosphatidylglycerol largely restored oxygenation and lung mechanics in most animals. Complete normalization with weaning from the ventilator, however, was achieved neither with liposomes nor with natural surfactant concentrate.

  2. Tin compounds interaction with membranes of egg lecithin liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Man, D.; Podolak, M. [Opole Univ. (Poland). Inst. of Physics


    This work is a continuation of earlier research concerning the influence of tin compounds on the dynamic properties of liposome membranes produced with lecithin hen egg yolks (EYL). The experiments were carried out at room temperature (about 25 C). Four tin compounds were chosen, including three organic ones, (CH{sub 3}){sub 4}Sn, (C{sub 2}H{sub 5}){sub 4}Sn and (C{sub 3}H{sub 7}){sub 3}SnCl, and one inorganic, SnCl{sub 2}. The investigated compounds were admixed to water dispersions of liposomes. The content of the admixture changed within the range 0 mol-% to 11 mol-% in proportion to EYL. Two spin probes were used in the experiment: 2,2,6,6-tetramethylpiperidine- 1-oxyl (TEMPO) and 2-ethyl-2-(15-methoxy-15-oxopentadecyl)-4,4-dimethyl-3-oxazolidinyloxyl (16-DOXYL-stearic acid), which penetrated through different areas of the membrane. It was found that tin compounds containing chlorine were the most active in interaction with liposome membranes. In the case of (C{sub 3}H{sub 7}){sub 3}SnCl, after exceeding 4% admixture content, an additional line appeared in the spectrum of the TEMPO probe which can be a result of formation of domain structures in the membranes of the studied liposomes. Compounds containing chlorine are of ionized form in water solution. The obtained results can thus mean that the activity of admixtures can be seriously influenced by their ionic character. In case of an admixture of non-ionic compounds the compound with a longer hydrocarbon chain displayed a slightly stronger effect on the spectroscopic parameters of the probes. (orig.)

  3. Radiation sterilization of antibiotic liposome formulations: A case study (United States)

    Botelho, M. L.; Cabo Verde, S.; Alves, L.; Belchior, A.; Reymão, J.; Trabulo, S.; Gaspar, M. M.; Cruz, M. E. M.; Simões, S.


    New liposome formulations for antimycobacterial purpose are under development in Portugal. The drug must be submitted to a sterilization process. In order to find out if gamma radiation could be applied, microbiological and chemical studies were developed based on ISO standards. The bioburden was determined, the main critical points of line production were detected and the sterilization dose was determined based on a chart control for bioburden. A preliminary maximum acceptable dose for product was found out based on the main functional parameters.

  4. EPR study of spermine interaction with multilamellar phosphatidylcholine liposomes. (United States)

    Momo, F; Wisniewska, A; Stevanato, R


    The interaction of spermine with egg-yolk phosphatidylcholine liposomes was investigated. The EPR spin labeling technique evidenced that spermine induces modifications of some membrane functions of biological interest like water permeability and is a possible modulator of diffusion processes for charged and polar molecules. The association constant for a hypothesized complex between spermine and the phosphate group of phosphatidylcholine was evaluated by enzymatic methods.

  5. Liposomes Came First: The Early History of Liposomology. (United States)

    Weissig, Volkmar


    It has been a long journey from Pliny the Elder (23-79 AD) to the FDA approval of the first injectable Nanomedicine in 1997. It has been a journey powered by intellectual curiosity, which began with sprinkling olive oil on seawater and culminated in playing around with smears of egg lecithin on microscopic slides. This brief review highlights how a few pairs of gifted hands attached to highly motivated brains have launched Liposome Technology.

  6. The Preparation of Matrine Liposome and Its Antiglioma Activity Study

    Directory of Open Access Journals (Sweden)

    Shao-Rong Han


    Full Text Available The aim of the study was to study the preparation of matrine liposome and its activity for resisting cells, to study the preparation of matrine liposome by orthogonal design, and to observe the inhibiting effect of matrine on glioma through MTT method, Flow Cytometer, and electron microscope. The results showed that we take the encapsulation efficiency as the index; the optimal preparation of matrine liposome is 100 mg of lecithin, 40 mg of cholesterol, phosphate buffered saline (PBS with pH value 6.4, and 40 mg of matrine. The result of MTT testing is shown that the tested group with medium and high dosage (0.75, 1.0, 1.25 mg/L of matrine has significant inhibiting rate to the growth of BT 325 cells. The A value in tested group with medium and high dosage is up to 0.19±0.03. The methods of Flow Cytometer and electron microscope prove that matrine can inhibit the growth of BT 325 cells. Matrine is active in inhibiting brain glioma.

  7. Manipulation and stretching of bacteria and liposomes by Microfluidics (United States)

    Zussman, Eyal; Salalha, Wael


    Microfluidic technology can be useful in lab-on-a-chip applications of biological assays, environmental monitoring, detection of toxic materials, as well as for assembly of nano- and micro-scale objects into more complex systems. In this work we focused on the orientation of rod-shaped bacteria (Bacillus) by employing shear flow and a high rate elongation flow, and stretching of giant liposomes with diameter size of tens of microns, which can be used as a simplified model for cell behavior. This was achieved by flows of dilute rod-like bacteria and liposome suspensions within a micro-channel by means of a capillary-driven motion. Fluidic alignment situations were tested, firstly by Venturi-like flow which produces a sufficiently converging and diverging flow, and secondly by sink-like flow in a converging microchannel. In the first method we found that the converging part of the flow aligns rod-like bacteria, whereas the diverging part disaligns them, while in the second method the rod-like bacteria can perfectly align along the streamlines. In addition we used the same technology to test liposome deformation while they are flowing through a Venturi-like microchannel. The microfluidics devices were fabricated from poly(dimethylsiloxane) (PDMS) by soft lithographic techniques.

  8. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia. (United States)

    Raj, Trisha A Soosay; Smith, Amanda M; Moore, Andrew S


    Vincristine (VCR) is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL), a disease that accounts for approximately one-third of all childhood cancer diagnoses. VCR's full therapeutic potential has been limited by dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory-motor neuropathy. In the last decade, however, the discovery that liposomal encapsulation of chemotherapeutics can modulate the pharmacokinetic characteristics of a compound has stimulated much interest in liposomal VCR (vincristine sulfate liposomal injection [VSLI]) formulations for the treatment of ALL and other hematological malignancies. Promising data from recent clinical trials investigating VSLI in adults with ALL resulted in US Food and Drug Administration approval for use in patients with Philadelphia chromosome (t[9;22]/BCR-ABL1) (Ph)-negative (Ph-) disease. Additional clinical trials of VSLI in adults and children with both Ph-positive (Ph+) and Ph- ALL are ongoing. Here we review the preclinical and clinical experience to date with VSLI for ALL.

  9. Effect of lysophosphatidylcholine on behavior and structure of phosphatidylcholine liposomes

    Institute of Scientific and Technical Information of China (English)

    陆敬泽; 徐育敏; 陈建文; 黄芬


    Differential scanning calorimetry (DSC), fluorescence polarization and X-ray diffraction were per-formed to investigate the kinetics of the micellar to the lamellar phase transition of dipalmitoylphosphatidylcholine/1-palmitoylphosphatidylcholine (16:0 LPC/DPPC) liposomes at gel phase. With a 16:0 LPC concentration up to 27 mol% only the sharp main transition with relatively high enthalpy (△H) values of DPPC was observed. Increasing 16 : 0 LPC concentration, the phase transition was broadened and the transition enthalpy was decreased and finally totally disappeared. The fluorescence probes of 3AS, 9AS, 12AS, and 16AP were employed, respectively, to detect the mo-bility of various sites of carbon chains of DPPC or 16:0 LPC/DPPC liposomes. It was shown that DPPC liposomes formed in the absence of 16:0 LPC always had a fluidity gradient in both gel and liquid-crystalline phase, while in the presence of 14.1 mol% and 27.0 mol% 16:0 LPC in the mixtures, the fluidity gradient tended to disappear below 40℃:

  10. In vivo hypertensive arterial wall uptake of radiolabeled liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Hodis, H.N.; Amartey, J.K.; Crawford, D.W.; Wickham, E.; Blankenhorn, D.H. (Univ. of Southern California School of Medicine, Los Angeles (USA))


    Using five sham-operated and seven aortic coarctation-induced hypertensive New Zealand White rabbits intravenously injected with neutral small unilamellar vesicles loaded with (111In)nitrilotriacetic acid, we demonstrated in vivo that the normal aortic arterial wall participates in liposome uptake and that this uptake is increased in the hypertensive aortic wall by approximately threefold (p less than or equal to 0.0001). Among the three regions examined, aortic arch, thoracic aorta, and lower abdominal aorta, the difference in uptake between the normotensive and hypertensive arterial walls was significantly different, p less than or equal to 0.05, p less than or equal to 0.0001, and p less than 0.05, respectively. The uptake by the different regions of the hypertensive arterial wall is consistent with the pathological changes present in these areas. Furthermore, the extent of liposome uptake by the aortic wall is strongly correlated with the height of the blood pressure (r = 0.85, p = 0.001, n = 11). We conclude that neutral small unilamellar liposomes can be used to carry agents into the arterial wall in vivo in the study of hypertensive vascular disease and could be especially useful for the delivery of pharmacologically or biologically active agents that would otherwise be inactivated within the circulation or are impermeable to the arterial wall.

  11. A first step toward liposome-mediated intracellular bacteriophage therapy. (United States)

    Nieth, Anita; Verseux, Cyprien; Barnert, Sabine; Süss, Regine; Römer, Winfried


    The emergence of antibiotic-resistant bacteria presents a severe challenge to medicine and public health. While bacteriophage therapy is a promising alternative to traditional antibiotics, the general inability of bacteriophages to penetrate eukaryotic cells limits their use against resistant bacteria, causing intracellular diseases like tuberculosis. Bacterial vectors show some promise in carrying therapeutic bacteriophages into cells, but also bring a number of risks like an overload of bacterial antigens or the acquisition of virulence genes from the pathogen. As a first step in the development of a non-bacterial vector for bacteriophage delivery into pathogen-infected cells, we attempted to encapsulate bacteriophages into liposomes. Here we report effective encapsulation of the model bacteriophage λeyfp and the mycobacteriophage TM4 into giant liposomes. Furthermore, we show that liposome-associated bacteriophages are taken up into eukaryotic cells more efficiently than free bacteriophages. These are important milestones in the development of an intracellular bacteriophage therapy that might be useful in the fight against multi-drug-resistant intracellular pathogens like Mycobacterium tuberculosis.

  12. Deformable liposomes and ethosomes: mechanism of enhanced skin delivery. (United States)

    Elsayed, Mustafa M A; Abdallah, Ossama Y; Naggar, Viviane F; Khalafallah, Nawal M


    Despite intensive research, the mechanisms by which vesicular systems deliver drugs into intact skin are not yet fully understood. In the current study, possible mechanisms by which deformable liposomes and ethosomes improve skin delivery of ketotifen under non-occlusive conditions were investigated. In vitro permeation and skin deposition behavior of deformable liposomes and ethosomes, having ketotifen both inside and outside the vesicles (no separation of free ketotifen), having ketotifen only inside the vesicles (free ketotifen separated) and having ketotifen only outside the vesicles (ketotifen solution added to empty vesicles), was studied using rabbit pinna skin. Results suggested that both the penetration enhancing effect and the intact vesicle permeation into the stratum corneum might play a role in improving skin delivery of drugs by deformable liposomes, under non-occlusive conditions, and that the penetration enhancing effect was of greater importance in case of ketotifen. Regarding ethosomes, results indicated that ketotifen should be incorporated in ethosomal vesicles for optimum skin delivery. Ethosomes were not able to improve skin delivery of non-entrapped ketotifen.

  13. Liposome-Based Delivery Systems in Plant Polysaccharides

    Directory of Open Access Journals (Sweden)

    Meiwan Chen


    Full Text Available Plant polysaccharides consist of many monosaccharide by α- or β-glycosidic bond which can be extracted by the water, alcohol, lipophile liquid from a variety of plants including Cordyceps sinensis, astragalus, and mushrooms. Recently, many evidences illustrate that natural plant polysaccharides possess various biological activities including strengthening immunity, lowering blood sugar, regulating lipid metabolism, antioxidation, antiaging, and antitumour. Plant polysaccharides have been widely used in the medical field due to their special features and low toxicity. As an important drug delivery system, liposomes can not only encapsulate small-molecule compound but also big-molecule drug; therefore, they present great promise for the application of plant polysaccharides with unique physical and chemical properties and make remarkable successes. This paper summarized the current progress in plant polysaccharides liposomes, gave an overview on their experiment design method, preparation, and formulation, characterization and quality control, as well as in vivo and in vitro studies. Moreover, the potential application of plant polysaccharides liposomes was prospected as well.

  14. AmBisome (liposomal amphotericin B): a comparative review. (United States)

    Boswell, G W; Buell, D; Bekersky, I


    AmBisome (NeXstarPharmaceuticals, San Dimas, CA) is a unilamellar liposomal formulation of amphotericin B that was recently approved for use as empirical treatment for presumed fungal infections in febrile neutropenic patients and for aspergillosis, candidiasis, and cryptococcosis infections refractory to amphotericin B. It is a small closed microscopic sphere (AmBisome remains as an intact sphere in vitro and for prolonged periods of time in vivo during the processes of systemic transport and pharmacologic action. As a consequence of its size and in vivo stability, AmBisome has physiochemical properties and a pharmacokinetic profile that are considerably different from those of currently available lipid-complexed amphotericin B formulations, with greatly increased area under the plasma concentration-time curve and much lower clearance at equivalent doses. AmBisome liposomes can be seen to accumulate at sites of fungal infection. Disruption of AmBisome liposomes occurs after attachment to the fungal cell wall and results in amphotericin B binding to fungal cell membrane ergosterol with subsequent cell lysis. AmBisome has been shown to penetrate the cell wall of both extracellular and intracellular forms of susceptible fungi.

  15. The p10 FAST protein fusion peptide functions as a cystine noose to induce cholesterol-dependent liposome fusion without liposome tubulation. (United States)

    Key, Tim; Sarker, Muzaddid; de Antueno, Roberto; Rainey, Jan K; Duncan, Roy


    The reovirus p10 fusion-associated small transmembrane (FAST) proteins are the smallest known membrane fusion proteins, and evolved specifically to mediate cell-cell, rather than virus-cell, membrane fusion. The 36-40-residue ectodomains of avian reovirus (ARV) and Nelson Bay reovirus (NBV) p10 contain an essential intramolecular disulfide bond required for both cell-cell fusion and lipid mixing between liposomes. To more clearly define the functional, biochemical and biophysical features of this novel fusion peptide, synthetic peptides representing the p10 ectodomains of ARV and NBV were analyzed by solution-state NMR spectroscopy, circular dichroism spectroscopy, fluorescence spectroscopy-based hydrophobicity analysis, and liposome binding and fusion assays. Results indicate that disulfide bond formation promotes exposure of hydrophobic residues, as indicated by bis-ANS binding and time-dependent peptide aggregation under aqueous conditions, implying the disulfide bond creates a small, geometrically constrained, cystine noose. Noose formation is required for peptide partitioning into liposome membranes and liposome lipid mixing, and electron microscopy revealed that liposome-liposome fusion occurs in the absence of liposome tubulation. In addition, p10 fusion peptide activity, but not membrane partitioning, is dependent on membrane cholesterol.

  16. Enhanced bactericidal potency of nanoliposomes by modification of the fusion activity between liposomes and bacterium

    Directory of Open Access Journals (Sweden)

    Ma YF


    Full Text Available Yufan Ma,1 Zhao Wang,1,2 Wen Zhao,1 Tingli Lu,1 Rutao Wang,1,2 Qibing Mei,1 Tao Chen1–3 1Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China; 2Shaanxi Liposome Research Center, Xi'an, Shaanxi, People's Republic of China; 3Xi'an Libang Pharmaceuticals Co, Ltd, Xi'an, People's Republic of China Background: Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of Pseudomonas to conventional antibiotics made it imperative to develop new liposome formulations to overcome these mechanisms, and investigate the fusion between liposome and bacterium. Methods: The rigidity, stability and charge properties of phospholipid vesicles were modified by varying the cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE, and negatively charged lipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol sodium salt (DMPG, 1,2-dimyristoyl-sn-glycero-3-phopho-L-serine sodium salt (DMPS, 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA, nature phosphatidylserine sodium salt from brain and nature phosphatidylinositol sodium salt from soybean concentrations in liposomes. Liposomal fusion with intact bacteria was monitored using a lipid-mixing assay. Results: It was discovered that the fluid liposomes-bacterium fusion is not dependent on liposomal size and lamellarity. A similar degree of fusion was observed for liposomes with a particle size from 100 to 800 nm. The fluidity of liposomes is an essential pre-request for liposomes fusion with bacteria. Fusion was almost completely inhibited by incorporation of cholesterol into fluid liposomes. The increase in the

  17. Ciprofloxacin in polyethylene glycol-coated liposomes: efficacy in rat models of acute or chronic Pseudomonas aeruginosa infection

    NARCIS (Netherlands)

    I.A.J.M. Bakker-Woudenberg (Irma); M.T. ten Kate (Marian); L. Guo; P. Working; J.W. Mouton (Johan)


    textabstractIn a previous study in experimental Klebsiella pneumoniae pneumonia, the therapeutic potential of ciprofloxacin was significantly improved by encapsulation in polyethylene glycol-coated ("pegylated") long-circulating (STEALTH) liposomes. Pegylated liposomal

  18. Impact of atomization technique on the stability and transport efficiency of nebulized liposomes harboring different surface characteristics. (United States)

    Lehofer, Bernhard; Bloder, Florian; Jain, Pritesh P; Marsh, Leigh M; Leitinger, Gerd; Olschewski, Horst; Leber, Regina; Olschewski, Andrea; Prassl, Ruth


    The objective of this study was to evaluate the impact of nebulization on liposomes with specific surface characteristics by applying three commercially available inhaler systems (air-jet, ultrasonic and vibrating-mesh). Conventional liposome formulations composed of phosphatidylcholine and cholesterol were compared to sterically stabilized PEGylated liposomes and cationic polymer coated liposomes.Liposomes of similar size (between 140 and 165 nm in diameter with polydispersity indices atomization process, while polymer coated and especially positively charged liposomes showed enhanced leakage. The release rates for the hydrophilic model drug system were highest for the vibrating-mesh nebulizers regardless of the surface characteristics of the liposomes (increasing from 10% to 20% and 50% for the conventional, PEGylated and positively charged formulations, respectively). In view of surface modified liposomes our data suggest that drug delivery via nebulization necessitates the finding of a compromise between nebulizer efficiency, formulation stability and drug release profile to accomplish the development of tailored formulations suitable for advanced inhalation therapy.

  19. Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration

    DEFF Research Database (Denmark)

    Agrawal, Ashish Kumar; Harde, Harshad; Thanki, Kaushik;


    The present study reports the folic acid (FA) functionalized insulin loaded stable liposomes with improved bioavailability following oral administration. Liposomes were stabilized by alternating coating of negatively charged poly(acrylic acid) (PAA) and positively charged poly(allyl amine...

  20. Ciprofloxacin in polyethylene glycol-coated liposomes: efficacy in rat models of acute or chronic Pseudomonas aeruginosa infection

    NARCIS (Netherlands)

    I.A.J.M. Bakker-Woudenberg (Irma); M.T. ten Kate (Marian); L. Guo; P. Working; J.W. Mouton (Johan)


    textabstractIn a previous study in experimental Klebsiella pneumoniae pneumonia, the therapeutic potential of ciprofloxacin was significantly improved by encapsulation in polyethylene glycol-coated ("pegylated") long-circulating (STEALTH) liposomes. Pegylated liposomal ciprofloxaci

  1. Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation

    Directory of Open Access Journals (Sweden)

    Hong SS


    Full Text Available Soon-Seok Hong,1 Ju Yeon Choi,2 Jong Oh Kim,2 Mi-Kyung Lee,3 So Hee Kim,4 Soo-Jeong Lim1 1Department of Bioscience and Bioengineering, Sejong University, Seoul, 2College of Pharmacy, Yeungnam University, Gyeongsan, 3College of Pharmacy, Woosuk University, Wanju-gun, Jeollabuk-do, 4College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon, Republic of Korea Abstract: Studies have highlighted the challenge of developing injectable liposomes as a paclitaxel (PTX carrier, a challenge attributable to the limitations in liposomal stability caused by PTX loading. Poor stability of PTX-loaded liposomes is caused by PTX-triggered aggregation or fusion of liposomal membranes and is exacerbated in the presence of PEGylated lipid. In the present study, the effect of triglyceride incorporation on the stability of PTX-loaded/PEGylated liposomes was explored. Incorporation of a medium chain triglyceride Captex 300 into saturated phosphatidylcholine (PC-based liposomes (1,2-dimyristoyl-sn-glycero-3-phosphocholine [DMPC]:cholesterol [CHOL]:N-(Carbonyl-methoxypolyethyleneglycol 2000-1, 2-distearoyl-sn-glycero-3-phospho-ethanolamine [PE-PEG], produced a fine, homogeneous, and membrane-filterable PTX-loaded liposomes fulfilling the requirement of an injectable lipid formulation. Triglyceride incorporation also greatly inhibited the time-dependent leakage of PTX from saturated PC-based liposomes, which appears to be mediated by the inhibition of liposome fusion. In contrast, triglyceride incorporation induced the destabilization and PTX leakage of unsaturated PC-based liposomes, indicating the opposite effect of triglyceride depending on the fluidity status of PC constituting the liposomal membrane. PTX release profile and the in vitro and in vivo anticancer efficacy of triglyceride-incorporated DMPC:CHOL:PE-PEG liposomes were similar to Taxol® while the toxicity of liposomal PTX was significantly lower than that of

  2. Tumor burden talks in cancer treatment with PEGylated liposomal drugs.

    Directory of Open Access Journals (Sweden)

    Yi-Yu Lin

    Full Text Available PURPOSE: PEGylated liposomes are important drug carriers that can passively target tumor by enhanced permeability and retention (EPR effect in neoplasm lesions. This study demonstrated that tumor burden determines the tumor uptake, and also the tumor response, in cancer treatment with PEGylated liposomal drugs in a C26/tk-luc colon carcinoma-bearing mouse model. METHODS: Empty PEGylated liposomes (NanoX and those encapsulated with VNB (NanoVNB were labeled with In-111 to obtain InNanoX and InVNBL in high labeling yield and radiochemical purity (all >90%. BALB/c mice bearing either small (58.4±8.0 mm(3 or large (102.4±22.0 mm(3 C26/tk-luc tumors in the right dorsal flank were intravenously administered with NanoVNB, InNanoX, InVNBL, or NanoX as a control, every 7 days for 3 times. The therapeutic efficacy was evaluated by body weight loss, tumor growth inhibition (using calipers and bioluminescence imaging and survival fraction. The scintigraphic imaging of tumor mouse was performed during and after treatment. RESULTS: The biodistribution study of InVNBL revealed a clear inverse correlation (r (2 = 0.9336 between the tumor uptake and the tumor mass ranged from 27.6 to 623.9 mg. All three liposomal drugs showed better therapeutic efficacy in small-tumor mice than in large-tumor mice. Tumor-bearing mice treated with InVNBL (a combination drug showed the highest tumor growth inhibition rate and survival fraction compared to those treated with NanoVNB (chemodrug only and InNanoX (radionuclide only. Specific tumor targeting and significantly increased tumor uptake after periodical treatment with InVNBL were evidenced by scintigraphic imaging, especially in mice bearing small tumors. CONCLUSION: The significant differences in the outcomes of cancer treatment and molecular imaging between animals bearing small and large tumors revealed that tumor burden is a critical and discriminative factor in cancer therapy using PEGylated liposomal drugs.

  3. Liposomal drug delivery system from laboratory to clinic

    Directory of Open Access Journals (Sweden)

    Kshirsagar N


    Full Text Available The main objective of drug delivery systems is to deliver a drug effectively, specifically to the site of action and to achieve greater efficacy and minimise the toxic effects compared to conventional drugs. Amongst various carrier systems, liposomes have generated a great interest because of their versatility. Liposomes are vesicular concentric bilayered structures, which are biocompatible, biodegradable and nonimmumnogenic. They can control the delivery of drugs by targeting the drug to the site of action or by site avoidance drug delivery or by prolonged circulation of drugs. Amphotericin B (Amp B remains the drug of choice in most systemic mycoses and also as a second line treatment for Kala azar. However, its toxic effects often limit its use. Although the liposome delivery system has been tried for several drugs, only a few have been used in patients due to the slow development of necessary large-scale pharmaceutical procedures. This paper reviews the development of the technique for liposomal Amphotericin B (L-Amp-LRC-1, FungisomeTM drug delivery system in our laboratory in collaboration with the department of Biochemistry, Delhi University in India and proving the safety and efficacy of this preparation in clinical practice. It also attempts to compare the efficacy and benefits of our product for Indian patients with those of similar products and it includes facts from the publications that flowed from our work. As compared to conventional Amp B, Fungisome is infused over a much shorter period requiring a smaller volume and no premedication. It was found to be safe in patients who had developed serious unacceptable toxicity with conventional Amp B. In renal transplant patients, Fungisome did not produce any nephrotoxicity. Fungisome is effective in fungal infections resistant to fluconazole, conventional Amp B and in virgin and resistant cases of visceral leishmaniasis. The cost of any drug is of great significance, especially in India

  4. Pegylation of Cationic Liposomes Encapsulating Soluble Leishmania Antigens (SLA) Reduces the Adjuvant Efficacy of Liposomes in Murine Model. (United States)

    Naseri, Hadi; Eskandari, Faezeh; Jaafari, Mahmoud Reza; Khamesipour, Ali; Abbasi, Azam; Badiee, Ali


    Although there have been several attempts to develop a vaccine against leishmaniasis; no vaccine in human has been developed yet. Liposomes consisting of 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) encapsulating soluble Leishmania antigens (SLA) enhance protective immunity of SLA against L. major infection in mice. However, they immobilized at the injection site because of their positive charge. To overcome the problem, shielding the surface charge with polyethylene glycol (PEGylation) was chosen in this study. Liposomal SLA consisting different concentrations of PEG (1.9-15% mol) were prepared. BALB/c mice were immunized three times in three weeks intervals with different formulations. Lesion development and parasite burden in footpad and spleen were evaluated to specify the type of generated immune response and extent of protection. Th1/Th2 cytokine profiles and IgG isotypes were also analyzed. The maximum protection was observed in mice immunized with Lip-SLA or pLip-SLA (1.9%) due to smaller footpad swelling, reduction in parasite load, an increase in IgG2a and IFN-γ production. Our results showed that immunization of mice with high level of PEG (>7.5%) did not improve protective immunity of liposomal SLA. The presence of PEG, particularly more than 3.75%, is not recommended for protection against leishmaniasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Application of magnetic liposomes for magnetically guided transport of muscle relaxants and anti-cancer photodynamic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Kuznetsov, Anatoly A.; Filippov, Victor I.; Alyautdin, Renat N.; Torshina, N.L.; Kuznetsov, O.A. E-mail:


    Magnetic liposomes containing submicron-sized ferromagnetic particles were prepared encapsulating the muscle relaxant drugs, diadony or diperony, for local anesthesia. Alternatively, metal phthalocyanines (Photosense or Teraphthal), sensitizers for photodynamic or catalytic cancer therapy were loaded into the magnetic liposomes. Animal trials demonstrated successful magnetically guided transport of the drug-loaded liposomes.

  6. In Vitro Gene Delivery Mediated by Asialofetuin-Appended Cationic Liposomes Associated with γ-Cyclodextrin into Hepatocytes

    Directory of Open Access Journals (Sweden)

    Keiichi Motoyama


    Full Text Available The purpose of this study is to evaluate in vitro gene delivery mediated by asialofetuin-appended cationic liposomes (AF-liposomes associating cyclodextrins (CyD/AF-liposomes as a hepatocyte-selective nonviral vector. Of various CyDs, AF-liposomes associated with plasmid DNA (pDNA and γ-cyclodextrin (γ-CyD (pDNA/γ-CyD/AF-liposomes showed the highest gene transfer activity in HepG2 cells without any significant cytotoxicity. In addition, γ-CyD enhanced the encapsulation ratio of pDNA with AF-liposomes, and also increased gene transfer activity as the entrapment ratio of pDNA into AF-liposomes was increased. γ-CyD stabilized the liposomal membrane of AF-liposomes and inhibited the release of calcein from AF-liposomes. The stabilizing effect of γ-CyD may be, at least in part, involved in the enhancing gene transfer activity of pDNA/γ-CyD/AF-liposomes. Therefore, these results suggest the potential use of γ-CyD for an enhancer of transfection efficiency of AF-liposomes.

  7. Application of surface-linked liposomal antigens to the development of vaccines that induce both humoral and cellular immunity. (United States)

    Uchida, Tetsuya; Taneichi, Maiko


    The first characteristic identified in surface-linked liposomal antigens was the ability to induce antigen-specific, IgE-selective unresponsiveness. These results remained consistent even when different coupling procedures were employed for antigens with liposomes or for liposomes with different lipid components. The potential usefulness of surface-linked liposomal antigens for application to vaccine development was further investigated. During this investigation, a significant difference was observed in the recognition of liposomal antigens by antigen-presenting cells between liposomes with different lipid components, and this difference correlated closely with the adjuvant activity of liposomes. In addition to this "quantitative" difference between liposomes with differential lipid components, a "qualitative" difference (i.e., a differential ability to induce cross-presentation) was observed between liposomes with different lipid components. Therefore, by utilizing the ability to induce cross-presentation, surface-linked liposomal antigens might be used to develop virus vaccines that would induce cytotoxic T lymphocyte (CTL) responses. We have successfully developed a liposome vaccine that is capable of inducing CTL responses against internal antigens of influenza viruses and thus removing virus-infected cells in the host. This CTL-based liposomal vaccine might be applicable to the development of vaccines against influenza and other viruses that frequently undergo changes in their surface antigenic molecules.

  8. Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake (United States)

    Li, Xiuying; Chen, Dan; Le, Chaoyi; Zhu, Chunliu; Gan, Yong; Hovgaard, Lars; Yang, Mingshi


    Background The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127). Methods The two types of liposomes, ie, PF127-inlaid liposomes and PF127-adsorbed liposomes, were prepared by a thin-film hydration method followed by extrusion, in which coumarin 6 was loaded as a fluorescence marker. A modified Franz diffusion cell mounted with the intestinal mucus of rats was used to study the diffusion characteristics of the two types of PF127 liposomes. Cell uptake studies were conducted in Caco-2 cells and analyzed using confocal laser scanning microcopy as well as flow cytometry. Results The diffusion efficiency of the two types of PF127-modified liposomes through intestinal rat mucus was 5–7-fold higher than that of unmodified liposomes. Compared with unmodified liposomes, PF127-inlaid liposomes showed significantly higher cellular uptake of courmarin 6. PF127-adsorbed liposomes showed a lower cellular uptake. Moreover, and interestingly, the two types of PF127-modified liposomes showed different cellular uptake mechanisms in Caco-2 cells. Conclusion PF127-inlaid liposomes with improved intestinal mucus-penetrating ability and enhanced cellular uptake might be a potential carrier candidate for oral drug delivery. PMID:22163166

  9. Efficient intracellular drug-targeting of macrophages using stealth liposomes directed to the hemoglobin scavenger receptor CD163

    DEFF Research Database (Denmark)

    Etzerodt, Anders; Maniecki, Maciej Bogdan; Graversen, Jonas Heilskov;


    by hydrophobic linkage of CD163-binding monoclonal antibodies to polyethylene glycol-coated liposomes ('stealth liposomes'). Targeting to the endocytic CD163 protein greatly increased the uptake of liposomes in CD163 transfected cells and macrophages as visualized by confocal microscopy and flow cytometry...

  10. Liposomal encapsulation of dexamethasone modulates cytotoxicity, inflammatory cytokine response, and migratory properties of primary human macrophages

    NARCIS (Netherlands)

    Bartneck, M.; Peters, F.M.; Warzecha, K.T.; Bienert, M.; Bloois, van L.; Trautwein, C.; Lammers, T.G.G.M.; Tacke, F.


    The encapsulation of drugs into liposomes aims to enhance their efficacy and reduce their toxicity. Corticosteroid-loaded liposomes are currently being evaluated in patients suffering from rheumatoid arthritis, atherosclerosis, colitis, and cancer. Here, using several different fluorophore-labeled f

  11. Gold conjugate-based liposomes with hybrid cluster bomb structure for liver cancer therapy. (United States)

    Zhang, Ning; Chen, Huan; Liu, Ai-Yun; Shen, Jia-Jia; Shah, Vishva; Zhang, Can; Hong, Jin; Ding, Ya


    Hybrid drug delivery system containing both organic and inorganic nanocarriers is expected to achieve its complementary advantages for the aim of improving the performance of antineoplastic drugs in tumor therapy. Here we report the use of liposomes and gold nanoparticles to construct a liposome with a hybrid Cluster Bomb structure and discuss its unique multi-order drug release property for liver tumor treatment. A very simple method is used for the hybrid liposome preparation and involves mixing two solutions containing liposomes loaded with either non-covalent or covalent Paclitaxel (PTX, namely free PTX or PTX-conjugated GNPs, respectively) by different ratio of volume (25:75, 50:50, 25:75, v/v). Various mixed liposomes were tested to determine the optimal conditions for maximum drug delivery. The optimized liposome was then tested using xenograft Heps tumor-bearing mice and showed the best efficacy for chemotherapeutic inhibition of tumor at PTX liposome: PTX-conjugated GNP liposome of 25:75 ratio (v/v). This system allows for simple and easy preparation while providing a more accurate site- and time-release mode for tumor treatment using antitumor drugs.

  12. Nebulization of liposomal rh-Cu/Zn-SOD with a novel vibrating membrane nebulizer. (United States)

    Wagner, A; Vorauer-Uhl, K; Katinger, H


    Liposomes are potential drug carriers for pulmonary drug delivery: They can be prepared from phospholipids, which are endogenous to the respiratory tract as a component of pulmonary surfactant, and at an appropriate dose liposomes do not pose a toxicological risk to this organ. Among the various categories of drug that benefit from liposomal entrapment is the anti-inflammatory enzyme superoxide dismutase, thus prolonging its biological half-life. The delivery of liposomes by nebulization is hampered by stability problems, like physical and chemical changes that may lead to chemical degradation and leakage of the encapsulated drug. Here we present data of liposomes aerosolized with a novel electronic nebulizer based on a vibrating membrane technology (PARI eFlow), which amends drawbacks like liposomes degradation and product release. The data acquisition included aerosol properties such as aerodynamic particle size, nebulization efficiency, and liposome leakage upon nebulization. In conclusion, this study shows the ability of the PARI eFlow to nebulize high amounts of liposomal recombinant human superoxide dismutase with reduced vesicle disruption tested in an enclosing experimental protocol.

  13. Administration of liposomal agents and blood clearance capacity of the mononuclear phagocyte system

    NARCIS (Netherlands)

    E.W.M. van Etten (Els); M.T. ten Kate (Marian); S.V. Snijders (Susan); I.A.J.M. Bakker-Woudenberg (Irma)


    textabstractAs liposomes are cleared from the circulation to a substantial extent by the phagocytic cells of the mononuclear phagocyte system (MPS), there is a question whether administration of liposome-based therapeutic agents interferes with clearance of infectious o

  14. Lipid rafts-mediated endocytosis and physiology-based cell membrane traffic models of doxorubicin liposomes. (United States)

    Li, Yinghuan; Gao, Lei; Tan, Xi; Li, Feiyang; Zhao, Ming; Peng, Shiqi


    The clathrin-mediated endocytosis is likely a major mechanism of liposomes' internalization. A kinetic approach was used to assess the internalization mechanism of doxorubicin (Dox) loaded cationic liposomes and to establish physiology-based cell membrane traffic mathematic models. Lipid rafts-mediated endocytosis, including dynamin-dependent or -independent endocytosis of noncaveolar structure, was a dominant process. The mathematic models divided Dox loaded liposomes binding lipid rafts (B) into saturable binding (SB) and nonsaturable binding (NSB) followed by energy-driven endocytosis. The intracellular trafficking demonstrated early endosome-late endosome-lysosome or early/late endosome-cytoplasm-nucleus pathways. The three properties of liposome structures, i.e., cationic lipid, fusogenic lipid, and pegylation, were investigated to compare their contributions to cell membrane and intracellular traffic. The results revealed great contribution of cationic lipid DOTAP and fusogenic lipid DOPE to cell membrane binding and internalization. The valid Dox in the nuclei of HepG2 and A375 cells treated with cationic liposomes containing 40mol% of DOPE were 1.2-fold and 1.5-fold higher than that in the nuclei of HepG2 and A375 cells treated with liposomes containing 20mol% of DOPE, respectively, suggesting the dependence of cell type. This tendency was proportional to the increase of cell-associated total liposomal Dox. The mathematic models would be useful to predict intracellular trafficking of liposomal Dox.

  15. Novel mucus-penetrating liposomes as a potential oral drug delivery system

    DEFF Research Database (Denmark)

    Li, Xiuying; Chen, Dan; Le, Chaoyi


    The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127).......The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127)....

  16. On the interaction of fluorophore-encapsulating PEGylated lecithin liposomes with hamster and human platelets

    NARCIS (Netherlands)

    Heger, M.; Salles, I.I.; van Vuure, W.; Deckmyn, H.; Beek, J.F.


    Polyethylene glycol (PEG)-grafted phosphatidylcholine liposomes are used as drug carriers due to their low immunogenicity and prolonged circulation time. The interaction between sterically stabilized lecithin liposomes and platelets has not been investigated before, and deserves to be subjected to

  17. Selective partitioning of cholesterol and a model drug into liposomes of varying size

    DEFF Research Database (Denmark)

    Decker, Christiane; Fahr, Alfred; Kuntsche, Judith;


    The resistance of a lipid bilayer with respect to a bending deformation generally depends on the presence of membrane additives such as sterols, cosurfactants, peptides, and drugs. As a consequence, the partitioning of membrane additives into liposomes becomes selective with respect to liposome s...

  18. Efficacy and safety of liposomal anthracyclines in phase I/II clinical trials. (United States)

    Alberts, David S; Muggia, Franco M; Carmichael, James; Winer, Eric P; Jahanzeb, Mohammad; Venook, Alan P; Skubitz, Keith M; Rivera, Edgardo; Sparano, Joseph A; DiBella, Nicholas J; Stewart, Simon J; Kavanagh, John J; Gabizon, Alberto A


    Preclinical studies have established the pharmacologic advantages of liposomal anthracyclines, including pharmacokinetic profiles after bolus dosing that resemble continuous infusion of conventional anthracyclines, increased drug concentrations in tumor cells compared with the surrounding tissues, and reduced toxicity relative to conventional anthracycline treatment. Based on these studies, many phase I and phase II clinical trials were conducted to assess the safety and potential activity of liposomal anthracyclines in the management of both solid and hematologic tumors. These studies provided valuable insight into the safety of pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), nonpegylated liposomal doxorubicin (Myocet [NPLD]), and liposomal daunorubicin (DaunoXome [DNX]) over a range of doses, either as single-agent therapy or in combination with other cytotoxic agents. Other liposomal anthracyclines in development may be well tolerated but their activity remains to be elucidated by clinical trials. The available data also suggest that liposomal anthracyclines have activity not only against tumor types with known sensitivity to conventional anthracyclines, but also potentially for tumors that are typically anthracycline-resistant. Despite the availability of clinical data from a wide variety of tumor types and patient populations, further studies of liposomal anthracycline therapy are needed to fully establish their safety, efficacy, and dosing in the treatment of these patients.

  19. Relationship between the adjuvant and cytotoxic effects of the positive charges and polymerization in liposomes. (United States)

    Gasparri, Julieta; Speroni, Lucía; Chiaramoni, Nadia Silvia; del Valle Alonso, Silvia


    Vaccine development today encounters a main obstacle, which is the need for effective adjuvants suitable for clinical trials. Aluminum salts, discovered 70 years ago and, very recently, MF59, are the only types of adjuvants currently used in vaccines licensed by the U.S. Food and Drug Administration. Liposomes represent an alternative approach to vaccine adjuvants. In this article, we describe the inflammatory response and biological effect of polymerization and the addition of positive charges in liposome formulations. Nonpolymerized cationic (NP(+)) liposomes significantly reduce metabolism in Vero cells after 24 hours. Correspondingly, both NP(+) and polymerized cationic (P(+)) liposomes reduce cell viability following a 48-hour incubation. Similar results were obtained with cells from the peritoneal cavities of mice. Paradoxically, those liposomes that presented clearly cytostatic or cytotoxic effects in vitro stimulated metabolism and had a mitogenic effect in vivo. Finally, the adjuvant effect was tested by immunization in BALB/c mice. The major effect was obtained with NP(+) liposomes. Accordingly, we also demonstrated that NP(+) liposomes injected into the dermis produced an outstanding inflammatory reaction, showing the histopathological characteristics of an inoculation granuloma. Thus, positive charge would play an important role in the immunoadjuvant effect of liposomes by conferring them cytotoxic capacity.

  20. Use of a passive equilibration methodology to encapsulate cisplatin into preformed thermosensitive liposomes. (United States)

    Woo, Janet; Chiu, Gigi N C; Karlsson, Göran; Wasan, Ellen; Ickenstein, Ludger; Edwards, Katarina; Bally, Marcel B


    A conventional, cholesterol-containing liposome formulation of cisplatin has demonstrated insignificant activity in clinical trials, due in part, to insufficient release of encapsulated content following localization within solid tumors. For this reason, the development of a triggered release liposome formulation is desirable. In this report, cisplatin was encapsulated into lysolipid-containing thermosensitive liposomes (LTSL) using a novel technique, which relies on the equilibration of cisplatin across the liposomal membrane at temperatures above the gel-to-liquid crystalline phase transition temperature (TC) of the bulk phospholipid. Mild heating and drug loading into LTSL did not induce morphological changes of the liposomes. In vitro data demonstrated that >95% of encapsulated cisplatin was released from LTSL within 5 min following mild heating at 42 degrees C, while liposomes exhibited 70% release of cisplatin at 42 degrees C, and cholesterol-containing liposomes exhibited negligible drug release at 42 degrees C. The pharmacokinetic profiles of LTSL- and TSL-cisplatin indicated that these formulations were rapidly eliminated from circulation (terminal t(1/2) of 1.09 and 2.83 h, respectively). The therapeutic utility of LTSL-cisplatin formulation will be based on strategies where hyperthermia is applied prior to the administration of the liposomal drug-a strategy similar to that used in the clinical assessment of LTSL-doxorubicin formulation.

  1. Uptake characteristics of liposomes by rat alveolar macrophages: influence of particle size and surface mannose modification. (United States)

    Chono, Sumio; Tanino, Tomoharu; Seki, Toshinobu; Morimoto, Kazuhiro


    The influence of particle size and surface mannose modification on the uptake of liposomes by alveolar macrophages (AMs) was investigated in-vitro and in-vivo. Non-modified liposomes of five different particle sizes (100, 200, 400, 1000 and 2000 nm) and mannosylated liposomes with 4-aminophenyl-alpha-D-mannopyranoside (particle size 1000 nm) were prepared, and the uptake characteristics by rat AMs in-vitro and in-vivo were examined. The uptake of non-modified liposomes by rat AMs in-vitro increased with an increase in particle size over the range of 100-1000 nm, and became constant at over 1000 nm. The uptake of non-modified liposomes by AMs after pulmonary administration to rats in-vivo increased with an increase in particle size in the range 100-2000 nm. The uptake of mannosylated liposomes (particle size 1000 nm) by rat AMs both in-vitro and in-vivo was significantly greater than that of non-modified liposomes (particle size 1000 nm). The results indicate that the uptake of liposomes by rat AMs is dependent on particle size and is increased by surface mannose modification.

  2. Influence of particle size on the distributions of liposomes to atherosclerotic lesions in mice. (United States)

    Chono, Sumio; Tauchi, Yoshihiko; Morimoto, Kazuhiro


    In order to confirm the efficacy of liposomes as a drug carrier for atherosclerotic therapy, the influence of particle size on the distribution of liposomes to atherosclerotic lesions in mice was investigated. In brief, liposomes of three different particle sizes (500, 200, and 70 nm) were prepared, and the uptake of liposomes by the macrophages and foam cells in vitro and the biodistributions of liposomes administered intravenously to atherogenic mice in vivo were examined. The uptake by the macrophages and foam cells increased with the increase in particle size. Although the elimination rate from the blood circulation and the hepatic and splenic distribution increased with the increase in particle size in atherogenic mice, the aortic distribution was independent of the particle size. The aortic distribution of 200 nm liposomes was the highest in comparison with the other sizes. Surprisingly, the aortic distribution of liposomes in vivo did not correspond with the uptake by macrophages and foam cells in vitro. These results suggest that there is an optimal size for the distribution of liposomes to atherosclerotic lesions.

  3. Noninvasive control of the transport function of fluorescent coloured liposomal nanoparticles (United States)

    Stelmashchuk, O.; Zherebtsov, E.; Zherebtsova, A.; Kuznetsova, E.; Vinokurov, A.; Dunaev, A.; Mamoshin, A.; Snimshchikova, I.; Borsukov, A.; Bykov, A.; Meglinski, I.


    The use of liposomal nanoparticles with an incorporated active substance is an innovative and promising approach to diagnostics and therapy. The application of liposomal nanoparticle-based drugs allows for targeted localized delivery, overcomes the natural barriers within the body effectively, and minimizes possible side effects. Liposomes are able to contain a variety of ingredients with practically no limitations to their chemical composition, chemical properties, or size of constituent molecules. This study evaluated the ability to control the passage of fluorescent dye-filled liposomes through the intestinal mucosal barrier after oral administration. For this purpose, the increase in transcutaneous registered fluorescence from tetrabromofluorescein dye was recorded and analysed. Fluorescence intensity was measured at the proximal end of the tail of an animal model after oral administration of the liposomes. Measurements were taken at the excitation wavelengths of 365 and 450 nm. The fluorescence intensity in the group treated with the fluorescent contrast agent encapsulated in liposomal particles increased 140% of the initial level, but in the group treated with pure contrast agent, the increase in detected fluorescence intensity did not exceed 110%. Mice that received empty liposomes as well as the control group did not demonstrate statistically significant changes in fluorescence intensity. A potential application of our results is an express laser optical method of monitoring the transport of orally administered liposomal particles. The results can be used to help create new optical tools for use in the development of new drugs and in high-throughput screening used during their testing.

  4. Synthesis of phthalocyanine conjugates with gold nanoparticles and liposomes for photodynamic therapy

    CSIR Research Space (South Africa)

    Nombona, N


    Full Text Available gold nanoparticles or encapsulated in liposomes. Cell viability studies showed the optimum phototoxic effect on non-malignant cells to be 4.5 J cm-2. The PDT effect of the liposome bound phthalocyanine showed extensive damage of the breast cancer cells...

  5. On the interaction of fluorophore-encapsulating PEGylated lecithin liposomes with hamster and human platelets

    NARCIS (Netherlands)

    Heger, M.; Salles, I.I.; van Vuure, W.; Deckmyn, H.; Beek, J.F.


    Polyethylene glycol (PEG)-grafted phosphatidylcholine liposomes are used as drug carriers due to their low immunogenicity and prolonged circulation time. The interaction between sterically stabilized lecithin liposomes and platelets has not been investigated before, and deserves to be subjected to s

  6. Distribution of technetium-99m PEG-liposomes during oligofructose-induced laminitis development in horses

    NARCIS (Netherlands)

    Underwood, Claire; Pollitt, Christopher C.; Metselaar, Josbert M.; Laverman, Peter; van Bloois, Louis; van den Hoven, Jolanda M.; Storm, G; van Eps, Andrew W.


    Liposomes are phospholipid nanoparticles used for targeted drug delivery. This study aimed to determine whether intravenous liposomes accumulate in lamellar tissue during laminitis development in horses so as to assess their potential for targeted lamellar drug delivery. Polyethylene-glycol (PEG) co


    NARCIS (Netherlands)



    The therapeutic effect of a combination of liposomal muramyl dipeptide (MDP) and 5-fluorouracil (5FU) was studied in a murine tumor model of hepatic metastases of the tumor cell line C26, a colon adenocarcinoma. Liposomal MDP (250 mug/kg body wt) and a low, nontoxic, dose of 5FU (10 mg/kg body wt) w


    NARCIS (Netherlands)

    Elferink, Marieke G.L.; Wit, Janny G. de; Driessen, Arnold J.M.; Konings, Wil N.


    Liposomes composed of tetraether lipids originating from the thermoacidophilic archaeon Sulfolobus acidocaldarius were analyzed for their stability and proton permeability from 20 degrees C up to 80 degrees C. At room temperature, these liposomes are considerably more stable and have a much lower pr

  9. Surface functionalization of liposomes with proteins and carbohydrates for use in anti-cancer applications (United States)

    Platt, Virginia M.

    Liposomes can be used to exploit the altered biology of cancer thereby increasing delivery of liposome-associated anti-cancer drugs. In this dissertation, I explore methods that utilize the unique cancer expression of the polymeric glycosaminoglycan hyaluronan (HA) and the HA receptor CD44 to target liposomes to tumors, using liposomes functionalized with proteins or oligosaccharides on their surface. To make it easier to prepare protein-functionalized liposomes, a non-covalent protein/liposome association method based upon metal chelation/his 6 interaction was devised and characterized. I evaluated non-covalent attachment of the prodrug converting enzyme yeast cytosine deaminase, the far-red fluorescent protein mKate, two antigens ovalbumin and the membrane proximal region of an HIV GAG and hyaluronidase, a HA-degrading enzyme. In Chapter 2, I describe the synthesis of hyaluronan-oligosaccharide (HA-O) lipid conjugates and their incorporation into liposomes to target CD44-overexpressing cancer cells. HA-O ligands of defined-length, up to 10 monosaccharides, were attached to lipids via various linkers by reductive amination. The HA-lipids were easily incorporated into liposomes but did not mediate binding of liposomes to CD44 overexpressing cells. In Chapter 3, I evaluate the capacity of tris-NTA-Ni-lipids incorporated within a liposome bilayer to associate with his6-tagged proteins. Tris-NTA-lipids of differing structures and avidities were used to associate yeast cytosine deaminase and mKate to the surface of liposomes. Two tris-NTA-lipids and a mono-NTA lipid associated his-tagged proteins to a 1:1 molar ratio in solution. The proteins remained active while associated with the liposome surface. When challenged in vitro with fetal calf serum, tris-NTA-containing liposomes retained his-tagged proteins longer than mono-NTA. However, the tris-NTA/his6 interaction was found to be in a dynamic state; free yeast cytosine deaminase rapidly competed with pre-bound m

  10. Liposomes as a carrier for oral administration of insulin: effect of formulation factors. (United States)

    Choudhari, K B; Labhasetwar, V; Dorle, A K


    The present work was undertaken to study the effect of liposome formulation factors on its efficiency as a carrier for oral administration of insulin. The insulin-liposomes were prepared by two methods: solvent evaporation hydration and solvent spherule evaporation, with various variables such as concentration of insulin (I), lecithin (L), cholesterol (C), and Tween-80 (T). It was found that the insulin-liposomes when administered orally could produce hypoglycaemia. Variation in liposome composition was found to affect the efficiency of liposome as a carrier for oral administration of insulin. A liposome system containing L, 100 mg; C, 20 mg; I, 150 units; T, 1 per cent v/v, and prepared by the solvent spherule evaporation method was found to be most effective. The effect of insulin-liposome had prolonged action in diabetes-induced rabbits compared with that in normal rabbits. The results of the insulin-liposome system were comparable with the action of 1 unit of insulin/kg administered subcutaneously.

  11. Process optimization by use of design of experiments: Application for liposomalization of FK506. (United States)

    Toyota, Hiroyasu; Asai, Tomohiro; Oku, Naoto


    Design of experiments (DoE) can accelerate the optimization of drug formulations, especially complexed formulas such as those of drugs, using delivery systems. Administration of FK506 encapsulated in liposomes (FK506 liposomes) is an effective approach to treat acute stroke in animal studies. To provide FK506 liposomes as a brain protective agent, it is necessary to manufacture these liposomes with good reproducibility. The objective of this study was to confirm the usefulness of DoE for the process-optimization study of FK506 liposomes. The Box-Behnken design was used to evaluate the effect of the process parameters on the properties of FK506 liposomes. The results of multiple regression analysis showed that there was interaction between the hydration temperature and the freeze-thaw cycle on both the particle size and encapsulation efficiency. An increase in the PBS hydration volume resulted in an increase in encapsulation efficiency. Process parameters had no effect on the ζ-potential. The multiple regression equation showed good predictability of the particle size and the encapsulation efficiency. These results indicated that manufacturing conditions must be taken into consideration to prepare liposomes with desirable properties. DoE would thus be promising approach to optimize the conditions for the manufacturing of liposomes.

  12. Liposomal encapsulation of the natural flavonoid fisetin improves bioavailability and antitumor efficacy. (United States)

    Seguin, Johanne; Brullé, Laura; Boyer, Renaud; Lu, Yen Mei; Ramos Romano, Miriam; Touil, Yasmine S; Scherman, Daniel; Bessodes, Michel; Mignet, Nathalie; Chabot, Guy G


    The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has shown antiangiogenic and anticancer properties. Because of fisetin limited water solubility, we designed a liposomal formulation and evaluated its biological properties in vitro and in Lewis lung carcinoma (LLC) bearing mice. A liposomal formulation was developed with DOPC and DODA-PEG2000, possessing a diameter in the nanometer range (173.5±2.4nm), a high homogeneity (polydispersity index 0.181±0.016) and high fisetin encapsulation (58%). Liposomal fisetin incubated with LLC cells were internalized, induced a typical fisetin morphological effect and increased the sub-G1 cell distribution. In vivo, liposomal fisetin allowed a 47-fold increase in relative bioavailability compared to free fisetin. The effect of liposomal fisetin on LLC tumor growth in mice at low dose (21mg/kg) allowed a higher tumor growth delay (3.3 days) compared to free fisetin at the same dose (1.6 day). Optimization of liposomal fisetin therapy was attempted by co-treatment with cyclophosphamide which led to a significant improvement in tumor growth delay (7.2 days) compared to cyclophosphamide with control liposomes (4.2 days). In conclusion, fisetin liposomes markedly improved fisetin bioavailability and anticancer efficacy in mice and this formulation could facilitate the administration of this flavonoid in the clinical setting.

  13. Development of paclitaxel-loaded liposomal systems with anti-her2 ...

    African Journals Online (AJOL)

    Purpose: To develop liposome formulations containing monoclonal antibody ... Keywords: Cancer, Anti-her2 antibody, Liposome, Paclitaxel, Targeted therapy, Cell culture .... Experiments were carried out in triplicates. .... High-energy input such as elevated production .... Themed Section: Vector Design And Drug Delivery.

  14. Ethosomes and liposomes as topical vehicles for azelaic acid: a preformulation study. (United States)

    Esposito, Elisabetta; Menegatti, Enea; Cortesi, Rita


    The basic properties and the in vitro release rate kinetics of azelaic acid (AA), alternatively vehiculated in different phospholipid-based vesicles such as ethosomes or liposomes, were investigated. Ethosomes were produced by a simple method based on addition of an aqueous phase to an ethanol solution (comprised between 20\\% and 45%, v/v) of soy phosphatidyl choline (5%, w/w) and AA (0.2%, w/w) under mechanical stirring. Liposomes were obtained by the same composition in the absence of ethanol with the reverse-phase evaporation method. Vesicle size was measured by photon correlation spectroscopy (PCS), evidencing smaller mean diameters and narrower dimensional distributions in the case of ethosomes with respect to liposomes. In order to obtain homogeneously sized vesicles, both ethosomal and liposomal dispersions were extruded through polycarbonate membranes with pores of calibrated diameter (400 nm and 200 nm). Vesicle morphology was characterized by freeze-fracture scanning electron microscopy (SEM) showing the presence of unilamellar vesicles both in liposome- and in ethosome-based dispersions. Free energy measurements of the vesicle bilayers were conducted by differential scanning calorimetry (DSC). AA diffusion from ethosomal or liposomal dispersions and from ethosomes and liposomes incorporated in a viscous gel was investigated by a Franz cell assembled with synthetic membranes. The release rate was more rapid from ethosomal systems than from liposomal systems. In particular, ethosomes produced by the highest ethanol concentration released AA more rapidly, and the same trend was found using viscous forms.

  15. Inhibition of the Growth of Plasmodium falciparum in Culture by Stearylamine-Phosphatidylcholine Liposomes

    Directory of Open Access Journals (Sweden)

    Gulam Mustafa Hasan


    Full Text Available We have examined the effect of stearylamine (SA in liposomes on the viability of Plasmodium falciparum in culture by studying the inhibition of incorporation of [3H]-hypoxanthine in the nucleic acid of parasites. Stearylamine in liposomes significantly inhibits the growth of the parasites depending on the phospholipids composition. The maximum inhibition was observed when SA was delivered through Soya phosphatidylcholine (SPC liposomes. The chain length of alkyl group and density of SA in liposomes play a significant role in inhibiting the growth of the parasites. Incorporation of either cholesterol or Distearylphosphatidylethanolamine−Methoxy-Polyethylene glycol-2000 (DSPE-mPEG-2000 in Soya phosphatidylcholine-stearylamine (SPC-SA liposomes improves the efficacy. Intraerythrocytic entry of intact SPC-SA liposomes into infected erythrocytes was visualized using fluorescent microscopy. No hemolysis was observed in uninfected erythrocytes, and slight hemolysis was noted in infected erythrocytes at high concentrations of SPC-SA liposomes. Overall, our data suggested SA in SPC-liposomes might have potential application in malaria chemotherapy.

  16. FTIR Characterization of the Secondary Structure of Insulin Encapsulated within Liposome

    Institute of Scientific and Technical Information of China (English)

    ZHANGXuan; HUANGLi-xin; NIESong-qing; QIXian-rong; ZHANGQiang


    Aim:To determine the secondary structure of insulin encapsulated within liposome.Methods:The secondary structure of native insulin,mixture of insulin with liposome(sample I) and insulin encapsulated within liposome(sample Ⅱ) were determined by FTIR(Fourier Transform Infrared) spectroscopy.Results:The secondary structure of insulin encspsulated within liposome(Ⅱ) are similar with the secondary structure of native insulin.The difference existed in the amount of α-helices (from 36% of insulin to 31% of sample Ⅱ)and β-sheet(from 48% of insulin to 51% of sample Ⅱ).The content of α-helices and β-sheet of insulin in sample I was found to be very close to that of sample Ⅱ.The results revealed that the insulin encapsulated within liposome possibly spread on the surface of liposome,without inserting into the liposome membrane.Coclusion:The secondary structure of insulin encapsulated within liposome is similar with the native insulin.

  17. Observation of inhomogeneity in the lipid composition of individual nanoscale liposomes

    DEFF Research Database (Denmark)

    Larsen, Jannik; Hatzakis, Nikos; Stamou, Dimitrios


    Liposomes, or vesicles, have been studied extensively both as models of biological membranes and as drug delivery vehicles. Typically it is assumed that all liposomes within the same preparation are identical. Here by employing pairs of fluorescently labeled lipids we demonstrated an up to 10-fold...

  18. Investigation of liposomes as carriers of sodium ascorbyl phosphate for cutaneous photoprotection. (United States)

    Foco, Alma; Gasperlin, Mirjana; Kristl, Julijana


    Long-term exposure of the skin to UV-A and UV-B radiation causes degenerative effect which can be decreased by scavenging reactive photochemical intermediates with antioxidants. In this study sodium ascorbyl phosphate (SAP), a very effective oxygen species scavenger, was encapsulated into liposomes in order to improve its penetration through the stratum corneum into the deeper layers of the skin. Two types of multilamellar vesicles were prepared, one from non-hydrogenated and the other from hydrogenated soybean lecithin, together with cholesterol, by the thin films method. They were characterized for size, polydispersity index, and zeta potential. In vitro diffusion of SAP and ex vivo penetration experiments were performed on pig ear epidermis membrane in a Franz diffusion cell. The size and zeta potential of liposomes containing SAP are significantly greater than those of empty liposomes. The upper limit of SAP entrapment efficiency was 8-10% in both types of liposomes. The stability of SAP in liposome formulations is much more influenced by storage temperature than by liposome composition. SAP penetrated through epidermis membrane significantly better from liposome dispersions than from water solution. The amount penetrating is much more influenced by the concentration of SAP in the formulation than by the lipid composition of liposomes. The SAP that penetrates through the epidermis reflects the active compound available to prevent or slow down the complex process of photodamage in the skin.

  19. A Rigorous Theory of Remote Loading of Drugs into Liposomes: Transmembrane Potential and Induced pH-Gradient Loading and Leakage of Liposomes (United States)

    Ceh; Lasic


    Many drugs are successfully loaded into preformed liposomes by using various gradients and transmembrane potential. Several experimental breakthroughs, however, have not been paralleled by theoretical understanding of the processes. Recently, we have developed a rigorous treatment of loading of weak acids and bases into liposomes. The model is based on equilibration of chemical potentials of permeable neutral species. Charged molecules are not allowed to permeate the membrane. Although this assumption is quite reasonable and experimental data fit the theoretical predictions rather well, we have extended the model of liposome loading. In the expanded model, terms which allow leakage of protons, buildup of the transmembrane pH gradient, an antiport exchange of various cations with protons, and leakage of other molecules from or into liposomes are added to the basic model.

  20. Liposomal bupivacaine versus traditional periarticular injection for pain control after total knee arthroplasty. (United States)

    Bagsby, Deren T; Ireland, Phillip H; Meneghini, R Michael


    The purpose of this study was to compare a novel liposomal bupivacaine to traditional peri-articular injection (PAI) in a multi-modal pain protocol for total knee arthroplasty (TKA). A retrospective cohort study compared 85 consecutive patients undergoing TKA with a traditional PAI of ropivacaine, epinephrine and morphine to 65 patients with a liposomal bupivacaine PAI. After the initial 24h, inpatient self-reported pain scores were higher in the liposomal bupivacaine group compared to the traditional PAI group (P = 0.04) and a smaller percentage (16.9%) of patients in the liposomal bupivacaine group rated their pain as "mild" compared to the traditional group (47.6%). Liposomal bupivacaine PAI provided inferior pain control compared to the less expensive traditional PAI in a multi-modal pain control program in patients undergoing TKA.

  1. Thermoresponsive pegylated bubble liposome nanovectors for efficient siRNA delivery via endosomal escape

    KAUST Repository

    Alamoudi, Kholod


    Improving the delivery of siRNA into cancer cells via bubble liposomes. Designing a thermoresponsive pegylated liposome through the introduction of ammonium bicarbonate salt into liposomes so as to control their endosomal escape for gene therapy.A sub-200 nm nanovector was fully characterized and examined for cellular uptake, cytotoxicity, endosomal escape and gene silencing.The siRNA-liposomes were internalized into cancer cells within 5 min and then released siRNAs in the cytosol prior to lysosomal degradation upon external temperature elevation. This was confirmed by confocal bioimaging and gene silencing reaching up to 90% and further demonstrated by the protein inhibition of both target genes.The thermoresponsiveness of ammonium bicarbonate containing liposomes enabled the rapid endosomal escape of the particles and resulted in an efficient gene silencing.

  2. Effect of Liposome Size on Internal RNA Replication Coupled with Replicase Translation. (United States)

    Sunami, Takeshi; Ichihashi, Norikazu; Nishikawa, Takehiro; Kazuta, Yasuaki; Yomo, Tetsuya


    Cell membranes inhibit the diffusion of intracellular materials, and compartment size can strongly affect the intracellular biochemical reactions. To assess the effect of the size of microcompartments on intracellular reactions, we constructed a primitive cell model consisting of giant liposomes and a translation-coupled RNA replication (TcRR) system. The RNA was replicated by Qβ replicase, which was translated from the RNA in giant liposomes encapsulating the cell-free translation system. A reporter RNA encoding the antisense strand of β-glucuronidase was introduced into the system to yield a TcRR read-out (green fluorescence). We demonstrate that TcRR was hardly detectable in larger liposomes (230 fL) but was more effective in smaller (7.7 fL) liposomes. Our experimental and theoretical results show that smaller microcompartments considerably enhance TcRR because the synthesized molecules, such as RNA and replicases, are more concentrated in smaller liposomes.

  3. High-Throughput Continuous Flow Production of Nanoscale Liposomes by Microfluidic Vertical Flow Focusing. (United States)

    Hood, Renee R; DeVoe, Don L


    Liposomes represent a leading class of nanoparticles for drug delivery. While a variety of techniques for liposome synthesis have been reported that take advantage of microfluidic flow elements to achieve precise control over the size and polydispersity of nanoscale liposomes, with important implications for nanomedicine applications, these methods suffer from extremely limited throughput, making them impractical for large-scale nanoparticle synthesis. High aspect ratio microfluidic vertical flow focusing is investigated here as a new approach to overcoming the throughput limits of established microfluidic nanoparticle synthesis techniques. Here the vertical flow focusing technique is utilized to generate populations of small, unilamellar, and nearly monodisperse liposomal nanoparticles with exceptionally high production rates and remarkable sample homogeneity. By leveraging this platform, liposomes with modal diameters ranging from 80 to 200 nm are prepared at production rates as high as 1.6 mg min(-1) in a simple flow-through process.

  4. Targeting of liposomes to HIV-1-infected cells by peptides derived from the CD4 receptor. (United States)

    Slepushkin, V A; Salem, I I; Andreev, S M; Dazin, P; Düzgüneş, N


    Liposomes can be targeted to HIV-infected cells by either reconstituting transmembrane CD4 in the membrane or covalently coupling soluble CD4 to modified lipids. We investigated whether synthetic peptides could be used as ligands for targeting liposomes. A synthetic peptide from the complementarity determining region 2 (CDR-2)-like domain of CD4 could bind specifically to HIV-infected cells and mediate the binding of peptide-coupled liposomes to these cells. A peptide from the CDR-3-like domain of CD4 inhibited HIV-induced syncytia formation, but failed to target liposomes to infected cells. This apparent discrepancy may be due to the requirement for a conformational change in the CD4 receptor for the CDR-3 region to interact with the HIV envelope protein. Our results demonstrate the feasibility of using synthetic peptides to target liposomes containing antiviral drugs to HIV-infected cells.

  5. Interactions between DMPC liposomes and the serum blood proteins HSA and IgG. (United States)

    Sabín, Juan; Prieto, Gerardo; Ruso, Juan M; Messina, Paula V; Salgado, Francisco J; Nogueira, Montserrat; Costas, Miguel; Sarmiento, Félix


    The interaction between two serum blood proteins, namely human serum albumin (HSA) and human immunoglobulin G (IgG), with 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) liposomes has been studied in detail using dynamic light scattering, flow cytometry, enzyme-linked immunosorbent assay (ELISA), electrophoretic mobility, differential scanning calorimetry (DSC), and surface tension measurements. HSA and IgG interact with liposomes forming molecular aggregates that remain stable at protein concentrations beyond those of total liposome coverage. Both HSA and IgG penetrate into the liposome bilayer. An ELISA assay indicates that the Fc region of IgG is the one that is immersed in the DMPC membrane. The liposome-protein interaction is mainly of electrostatic nature, but an important hydrophobic contribution is also present.

  6. Cancer Immunotherapy Utilized Bubble Liposomes and Ultrasound as Antigen Delivery System (United States)

    Oda, Yusuke; Otake, Shota; Suzuki, Ryo; Otake, Shota; Nishiie, Norihito; Hirata, Keiichi; Taira, Yuichiro; Utoguchi, Naoki; Maruyama, Kazuo


    In dendritic cells (DCs)-based cancer immunotherapy, it is important to present the epitope peptide derived from tumor associated antigens (TAAs) on MHC class I in order to induce tumor specific cytotoxic T lymphocytes (CTLs). However, MHC class I molecules generally present the epitope peptides derived from endogenous antigens for DCs but not exogenous ones such as TAAs. Recently, we developed the novel liposomal bubbles (Bubble liposomes) encapsulating perfluoropropane nanobubbles. In this study, we attempted to establish the novel antigen delivery system to induce MHC class I presentation using the combination of ultrasound and Bubble liposomes. Using ovalbumin (OVA) as model antigen, the combination of Bubble liposomes and ultrasound exposure for the DC could induce MHC class I presentation. In addition, the viability of DCs was more than 80%. These results suggest that Bubble liposomes might be a novel ultrasound enhanced antigen delivery tool in DC-based cancer immunotherapy.

  7. Preparation approaches of the coated capillaries with liposomes in capillary electrophoresis. (United States)

    Mei, Jie; Tian, Yan-Ping; He, Wen; Xiao, Yu-Xiu; Wei, Juan; Feng, Yu-Qi


    The use of liposomes as coating materials in capillary electrophoresis has recently emerged as an important and popular research area. There are three preparation methods that are commonly used for coating capillaries with liposomes, namely physical adsorption, avidin-biotin binding and covalent coupling. Herein, the three different coating methods were compared, and the liposome-coated capillaries prepared by these methods were evaluated by studying systematically their EOF characterization and performance (repeatability, reproducibility and lifetime). The amount of immobilized phospholipids and the interactions between liposome or phospholipid membrane and neutral compounds for the liposome-coated capillaries prepared by these methods were also investigated in detail. Finally, the merits and disadvantages for each coating method were reviewed.

  8. Aptamer-Modified Temperature-Sensitive Liposomal Contrast Agent for Magnetic Resonance Imaging. (United States)

    Zhang, Kunchi; Liu, Min; Tong, Xiaoyan; Sun, Na; Zhou, Lu; Cao, Yi; Wang, Jine; Zhang, Hailu; Pei, Renjun


    A novel aptamer modified thermosensitive liposome was designed as an efficient magnetic resonance imaging probe. In this paper, Gd-DTPA was encapsulated into an optimized thermosensitive liposome (TSL) formulation, followed by conjugation with AS1411 for specific targeting against tumor cells that overexpress nucleolin receptors. The resulting liposomes were extensively characterized in vitro as a contrast agent. As-prepared TSLs-AS1411 had a diameter about 136.1 nm. No obvious cytotoxicity was observed from MTT assay, which illustrated that the liposomes exhibited excellent biocompatibility. Compared to the control incubation at 37 °C, the liposomes modified with AS1411 exhibited much higher T1 relaxivity in MCF-7 cells incubated at 42 °C. These data indicate that the Gd-encapsulated TSLs-AS1411 may be a promising tool in early cancer diagnosis.

  9. Imaging phospholipid conformational disorder and packing in giant multilamellar liposome by confocal Raman microspectroscopy. (United States)

    Noothalapati, Hemanth; Iwasaki, Keita; Yoshimoto, Chikako; Yoshikiyo, Keisuke; Nishikawa, Tomoe; Ando, Masahiro; Hamaguchi, Hiro-O; Yamamoto, Tatsuyuki


    Liposomes are closed phospholipid bilayer systems that have profound applications in fundamental cell biology, pharmaceutics and medicine. Depending on the composition (pure or mixture of phospholipids, presence of cholesterol) and preparation protocol, intra- and inter-chain molecular interactions vary leading to changes in the quality (order and packing) of liposomes. So far it is not possible to image conformational disorders and packing densities within a liposome in a straightforward manner. In this study, we utilized confocal Raman microspectroscopy to visualize structural disorders and packing efficiency within a giant multilamellar liposome model by focusing mainly on three regions in the vibrational spectrum (CC stretching, CH deformation and CH stretching). We estimated properties such as trans/gauche isomers and lateral packing probability. Interestingly, our Raman imaging studies revealed gel phase rich domains and heterogeneous lateral packing within the giant multilamellar liposome. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Preparation and property analysis of a hepatocyte targeting pH-sensitive liposome

    Institute of Scientific and Technical Information of China (English)

    Si-Yuan Wen; Xiao-Hong Wang; Li Lin; Wei Guan; Sheng-Qi Wang


    AIM: To develop a hepatocyte targeting pH-sensitive liposome for drug delivery based on active targeting technology mediated by asialoglycoprotein receptors.METHODS: Four types of targeting molecules with galactose residue were synthesized and mixed with pH-sensitive lipids DC-chol/DOPE to prepare liposome with integrated property of hepatocyte specificity and pH sensitivity. Liposome 18-gal was selected with the best transfection activity through cellular uptake experiment. Property analysis was made through experiments of competitive inhibition of receptors,red blood cell hemolysis,in vitro cytotoxicity test by MTS assay and mediation of inhibitory effects of antisense phosphorothioate ODN on gene expression, etc.RESULTS: Liposome L8-gal had the desired properties of hepatocyte specificity, pH sensitivity, low cytotoxicity, and high transfection efficiency.CONCLUSION: Liposome 18-gal can be further developed as a potential hepatocyte- targeting delivery system.

  11. Role of liposome in treatment of overactive bladder and interstitial cystitis

    Directory of Open Access Journals (Sweden)

    Shih-Ya Hung


    Full Text Available Intravesical (local therapy of agents has been effective in delaying or preventing recurrence of superficial bladder cancer. This route of drug administration has also shown tremendous promise in the treatment of interstitial cystitis/painful bladder syndrome (IC/PBS and overactive bladder without systemic side effects. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core. They can incorporate drug molecules, both hydrophilic and hydrophobic, and show greater uptake into cells via endocytosis. Intravesical liposomes have therapeutic effects on IC/PBS patients, mainly because of their ability to form a protective lipid film on the urothelial surface. Recent studies have shown the sustained efficacy and safety of intravesical instillation of botulinum toxin formulated with liposomes (lipo-BoNT for the treatment of refractory overactive bladder This review considers the current status of intravesical liposomes or liposomal mediated drug delivery for the treatment of IC/PBS and overactive bladder.

  12. Liposomal bortezomib nanoparticles via boronic ester prodrug formulation for improved therapeutic efficacy in vivo. (United States)

    Ashley, Jonathan D; Stefanick, Jared F; Schroeder, Valerie A; Suckow, Mark A; Kiziltepe, Tanyel; Bilgicer, Basar


    In this study, we describe the development of liposomal bortezomib nanoparticles, which was accomplished by synthesizing bortezomib prodrugs with reversible boronic ester bonds and then incorporating the resulting prodrugs into the nanoparticles via surface conjugation. Initially, several prodrug candidates were screened based upon boronic ester stability using isobutylboronic acid as a model boronic acid compound. The two most stable candidates were then selected to create surface conjugated bortezomib prodrugs on the liposomes. Our strategy yielded stable liposomal bortezomib nanoparticles with a narrow size range of 100 nm and with high reproducibility. These liposomal bortezomib nanoparticles demonstrated significant proteasome inhibition and cytotoxicity against multiple myeloma cell lines in vitro and remarkable tumor growth inhibition with reduced systemic toxicity compared to free bortezomib in vivo. Taken together, this study demonstrates the incorporation of bortezomib into liposomal nanoparticles via reversible boronic ester bond formation to enhance the therapeutic index for improved patient outcome.

  13. A simplified method to attach antibodies on liposomes by biotin-streptavidin affinity for rapid and economical screening of targeted liposomes. (United States)

    Papadia, Konstantina; Markoutsa, Eleni; Antimisiaris, Sophia G


    The biotin-Streptavidin (STREP) technique for attachment of monoclonal antibodies (mAbs) (or other ligand types) on liposome surface offers high attachment yield, however it is time consuming and expensive due to the number of steps used and the consumption of large quantities of STREP. Herein, a simplified, fast and economic technique, by incubating pre-mixed biotin-mAb/STREP with biotin-liposomes, at a 3:1:1 biotin-mAb/STREP/biotin-LIP ratio (mol/mol/mol) was evaluated. The physichochemical properties, final mAb attachment yield and targeting potential of liposomes decorated with an anti-transferrin receptor mAb (TfR-mAb), prepared by the simple method (SM) and the conventional method (CM), were compared. The vesicle uptake by hCMEC/D3 cells (known to overexpress TfR) were considered as a measure of liposome targeting capability. Results show that both targeted liposome types (SM and CM) have small size (mean diameters around 150 nm), low poly-dispersity (approx. 0.20) and similar mAb attachment yield (between 64-88%). However, the uptake of the SM-liposomes is slightly lower compared to CM-LIP (24-30% decrease), suggesting that the modulated conformation of mAbs on the liposome surface (triplets attached to one single STREP molecule) results in decreased targeting capability. Nevertheless, the simpler and faster one-step preparation procedure which has very high lipid recovery (> 95%) compared to the CM (50-60%) and 15-30 times lower consumption of STREP, may be a good alternative for initial screening of various mAbs as ligands for targeted liposomal or other nanotechnologies, during pre-clinical development.

  14. Effective mucoadhesive liposomal delivery system for risedronate: preparation and in vitro/in vivo characterization

    Directory of Open Access Journals (Sweden)

    Jung IW


    Full Text Available Il-Woo Jung, Hyo-Kyung HanCollege of Pharmacy, Dongguk University-Seoul, Ilsan-Donggu, Goyang, Republic of KoreaAbstract: In this work, we aimed to develop chitosan-coated mucoadhesive liposomes ­containing risedronate to improve intestinal drug absorption. Liposomes containing risedronate were prepared with 1,2-distearoryl-sn-glycero-3-phosphocholine and distearoryl-sn-glycero-3-[phospho-rac-(1-glycerol] using the freeze-drying method, with subsequent coating of the anionic surfaces of the liposomes with chitosan. The in vitro characteristics of the chitosan-coated liposomes were investigated, including their stability, mucoadhesiveness, and Caco-2 cell permeability. This formulation was stable in simulated gastric and intestinal fluids, with the percentage of drug remaining in the liposomes being more than 90% after 24 hours of incubation. Chitosan-coated liposomes also showed strong mucoadhesive properties, implying potential electrostatic interaction with the mucous layer in the gastrointestinal tract. Compared with the untreated drug, chitosan-coated liposomes significantly enhanced the cellular uptake of risedronate, resulting in an approximately 2.1–2.6-fold increase in Caco-2 cells. Further, the chitosan-coated liposomes increased the oral exposure of risedronate by three-fold in rats. Taken together, the results of this study suggest that chitosan-coated liposomes containing risedronate should be effective for improving the bioavailability of risedronate.Keywords: cellular uptake, bioavailability, mucoadhesiveness, liposome, chitosan

  15. Mechanosensitive liposomes as artificial chaperones for shear-driven acceleration of enzyme-catalyzed reaction. (United States)

    Natsume, Tomotaka; Yoshimoto, Makoto


    Mechanosensitive liposomes were prepared and applied to continuously accelerate the glucose oxidase (GO) reaction in shear flow. The liposome membrane was composed of a ternary lipid mixture containing 20 mol % negatively charged lipid and 30 mol % cholesterol. The liposomes encapsulating GO and catalase were passed through microtubes with inner diameter of 190 or 380 μm at 25 °C to induce the catalytic oxidation of 10 mM glucose with simultaneous decomposition of H2O2 produced. The liposomal GO showed significantly low reactivity in the static liquid system because of the permeation resistance of lipid membranes to glucose. On the other hand, the enzyme activity of liposomal GO observed at the average shear rate of 7.8 × 10(3) s(-1) was significantly larger than its intrinsic activity free of mass transfer effect in the static liquid system. The structure of liposomes was highly shear-sensitive as elucidated on the basis of shear rate-dependent physical stability of liposomes and membrane permeability to 5(6)-carboxyfluorescein as well as to GO. Thus, the above shear-driven acceleration of GO reaction was indicated to be caused by the free GO molecules released from the structurally altered liposomes at high shear rates. Moreover, the shear-induced denaturation of free GO was completely depressed by the interaction with the sheared liposomes with the chaperone-like function. The shear-sensitive liposomal GO system can be a unique catalyst that continuously accelerates and also decelerates the oxidation reaction depending on the applied shear rate.

  16. Preparation, characterization, and in vivo evaluation of intranasally administered liposomal formulation of donepezil

    Directory of Open Access Journals (Sweden)

    Al Asmari AK


    Full Text Available Abdulrahman K Al Asmari,1 Zabih Ullah,1 Mohammad Tariq,1 Amal Fatani21Department of Research, Prince Sultan, Military Medical City, 2Department of Pharmacy, King Saud University, Riyadh, Saudi ArabiaAbstract: The adequate amount of drug delivery to the brain in neurological patients is a major problem faced by the physicians. Recent studies suggested that intranasal administration of liposomal formulation may improve the drug delivery to the brain. In the present study, an attempt was made to study the brain bioavailability of commonly used anti-Alzheimer drug donepezil (DNP liposomal formulation by intranasal route in rats. We adopted the thin layer hydration technique for the preparation of liposomes by using cholesterol, polyethylene glycol, and 1,2-distearyl-sn-glycero-3-phosphocholine (DSPC. The prepared liposomes were characterized by determining particle size, shape, surface morphology, zeta potential, encapsulation efficiency, and in vitro release of DNP. The pharmacokinetic parameters of liposomal DNP in plasma and brain of rats were determined following oral and nasal administration. The results of this study showed that the DNP liposomal formulation was stable with a consistent size (102±3.3 nm and shape. The prepared liposomes showed high encapsulation efficiency (84.91%±3.31% and sustained-release behavior. The bioavailability of DNP in plasma and brain increased significantly (P<0.05 after administration of liposomal formulation by the intranasal route. Histopathological examination showed that the formulation was safe and free from toxicity. It can be concluded that the nasal administration of liposomal preparation may provide an efficient and reliable mode of drug delivery to the central nervous system.Keywords: donepezil, intranasal, liposomes, bioavailability, blood–brain barrier

  17. Prolonged hypoglycemic effect in diabetic dogs due to subcutaneous administration of insulin in liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Stevenson, R.W.; Patel, H.M.; Parsons, J.A.; Ryman, B.E.


    The biologic action of insulin entrapped in liposomes (phospholipid vesicles) has been investigated following subcutaneous injection to dogs made diabetic with a combination of alloxan and streptozotocin. The fate of the liposomally entrapped material was determined by injecting rats subcutaneously with either /sup 125/I-insulin or the labeled polysaccharide /sup 14/C-inulin, incorporated in liposomes labeled with /sup 3/H-cholesterol. Injection of liposome insulin (0.75 U/kg) to five diabetic dogs resulted in a mean (+/- SEM) blood glucose fall from 16.4 +/- 0.8 to 2.9 +/- 0.4 mmol/L. The glucose level had still not returned to baseline after 24 h and, correspondingly, immunoreactive insulin (IRI) could still be detected in frozen and thawed plasma 24 h after injection. In contrast, the hypoglycemic effect of the same dose of free insulin with or without empty liposomes virtually ended within 8 h and IRI levels returned to baseline by 3 h after injection. In experiments on rats with liposomally entrapped /sup 125/I-insulin or /sup 14/C-inulin the proportion of the injected dose of tracer recoverable by excision of the injection site remained constant after about 1 h and 70% of the dose was still fixed in subcutaneous tissue for at least 5 h thereafter. When the plasma collected 3 h after subcutaneous injection of labeled liposomes containing /sup 125/I-insulin was passed through a column of Sepharose 6B, 50-75% of the /sup 125/I-activity was found in the fractions associated with intact liposomes. One possibility for the persistence of the hypoglycemic effect and of measurable IRI following injection of liposome insulin could be the presence of intact liposomes in the circulation for many hours after adsorption had ceased.

  18. Optimization of formulation variables of benzocaine liposomes using experimental design. (United States)

    Mura, Paola; Capasso, Gaetano; Maestrelli, Francesca; Furlanetto, Sandra


    This study aimed to optimize, by means of an experimental design multivariate strategy, a liposomal formulation for topical delivery of the local anaesthetic agent benzocaine. The formulation variables for the vesicle lipid phase uses potassium glycyrrhizinate (KG) as an alternative to cholesterol and the addition of a cationic (stearylamine) or anionic (dicethylphosphate) surfactant (qualitative factors); the percents of ethanol and the total volume of the hydration phase (quantitative factors) were the variables for the hydrophilic phase. The combined influence of these factors on the considered responses (encapsulation efficiency (EE%) and percent drug permeated at 180 min (P%)) was evaluated by means of a D-optimal design strategy. Graphic analysis of the effects indicated that maximization of the selected responses requested opposite levels of the considered factors: For example, KG and stearylamine were better for increasing EE%, and cholesterol and dicethylphosphate for increasing P%. In the second step, the Doehlert design, applied for the response-surface study of the quantitative factors, pointed out a negative interaction between percent ethanol and volume of the hydration phase and allowed prediction of the best formulation for maximizing drug permeation rate. Experimental P% data of the optimized formulation were inside the confidence interval (P < 0.05) calculated around the predicted value of the response. This proved the suitability of the proposed approach for optimizing the composition of liposomal formulations and predicting the effects of formulation variables on the considered experimental response. Moreover, the optimized formulation enabled a significant improvement (P < 0.05) of the drug anaesthetic effect with respect to the starting reference liposomal formulation, thus demonstrating its actually better therapeutic effectiveness.

  19. Chitosan coated vancomycin hydrochloride liposomes: Characterizations and evaluation. (United States)

    Yang, Zhenlei; Liu, Junli; Gao, Jinhua; Chen, Shilei; Huang, Guihua


    The present work evaluated the feasibility of chitosan coated liposomes (c-Lips) for the intravenous delivery of vancomycin hydrochloride (VANH), a water-soluble antibiotic for the treatment of gram-positive bacterial infections like osteomyelitis, arthritis, endocarditis, pneumonia, etc. The objective of this research was to develop a suitable drug delivery system in vivo which could improve therapeutic efficacy and decrease side effects especially nephrotoxicity. Firstly, the vancomycin hydrochloride liposomes (VANH-Lips) were prepared by modified reverse phase evaporation method, then the chitosan wrapped vancomycin hydrochloride liposomes (c-VANH-Lips) nanosuspension was formulated by the method of electrostatic deposition. Based on the optimized results of single-factor screening experiment, the c-VANH-Lips were found to be relatively uniform in size (220.40 ± 3.56 nm) with a narrow polydispersity index (PI) (0.21 ± 0.03) and a positive zeta potential (25.7 ± 1.12 mV). The average drug entrapment efficiency (EE) and drug loading (DL) were 32.65 ± 0.59% and 2.18 ± 0.04%, respectively. The in vitro release profile of c-VANH-Lips possessed a sustained release Characterization and the release behavior was in accordance with the Weibull equation. Hemolysis experiments showed that its intravenous injection had preliminary safety. In vivo, after intravenous injection to mice, c-VANH-Lips showed a longer retention time and higher AUC values compared with the VANH injection (VANH-Inj) and VANH-Lips. In addition, biodistribution results clearly demonstrated that c-VANH-Lips preferentially decreased the drug distribution in kidney of mice after intravenous injection. These results revealed that injectable c-VANH-Lips may serve as a promising carrier for VANH to increase therapeutic efficacy on gram-positive bacterial infections and reduce nephrotoxicity, which provides significantly clinical value for long-term use of VANH.

  20. Liposome-coated lipoplex-based carrier for antisense oligonucleotides. (United States)

    Wyrozumska, Paulina; Meissner, Justyna; Toporkiewicz, Monika; Szarawarska, Marta; Kuliczkowski, Kazimierz; Ugorski, Maciej; Walasek, Marta A; Sikorski, Aleksander F


    The chemical nature of genetic drugs (e.g. antisense oligonucleotides, siRNA, vectors) requires a suitable carrier system to protect them from enzymatic degradation without changing their properties and enable efficient delivery into target cells. Lipid vectors for nucleic acid delivery that have been widely investigated for years can be very effective. As the majority of attempts made in the field of cancer gene therapy have focused on solid tumors, while blood cancer cells have attracted less attention, the latter became the subject of our investigation. The lipid carrier proposed here is based on liposomes constructed by others but the lipid composition is original. A liposome-coated lipoplex (L-cL) consists of a core arising from complexation of positively charged lipid and negatively charged oligodeoxynucleotide (ODN) or plasmid DNA coated by a neutral or anionic lipid bilayer. Moreover, our lipid vector demonstrates size stability and is able to retain a high content of enclosed plasmid DNA or antisense oligodeoxynucleotides (asODNs). Observed transfection efficacies of the tested preparation using a plasmid coding for fluorescent protein were up to 60-85% of examined leukemia cells (Jurkat T and HL-60 lines) in the absence or the presence of serum. When BCL‑2 asODN was encapsulated in the L-cL, specific silencing of this gene product at both the mRNA and protein level and also a markedly decreased cell survival rate were observed in vitro. Moreover, biodistribution analysis in mice indicates prolonged circulation characteristic for PEG-modified liposomal carriers. Experiments on tumor-engrafted animals indicate substantial inhibition of tumor growth.

  1. Preparation of liposomal brucine and its pharmaceutical/pharmacodynamic characterization

    Institute of Scientific and Technical Information of China (English)

    Xiang-qi QIN; Yuan YUAN; Chang-sheng LIU; Qiu-yun WANG; Xi SHEN; Bai-can YANG


    Aim:To prepare a novel transdermal preparation of liposomal brucine (LB) and investigate its pharmaceutical/pharmacodynamic characterization. Methods:LB was prepared by a modified ethanol-dripping method. Its drug encapsulation efficiency (EE),particle size,in vitro release,and skin permeation were studied.Furthermore,a safety evaluation and pharmacodynamic analysis of LB,including acute dermal toxicity,skin irritation,and analgesic and anti-inflammatory effects were investigated. Results:the EE of LB was 72% and the mean particle size of the liposomes was 55.4 nm. The in vitro release profile indicated that less than 68% of the encapsulated brucine was released in 10 h. A skin permeation study showed that compared with the free brucine,LB exhibited higher cumulative drug permeation through the skin and lower drug accumulation in skin tissue,indicative of an obvious promotion of skin permeation with liposomal encapsulation.The acute dermal LDs0 of LB was greater than 100 mg/kg (brucine content) and skin irritation tests revealed that LB had no irritation to both integrity and broken skin. A pharmacodynamic evaluation of LB was performed by xylene-induced mouse ear edema test and acetic acid-induced writhing test at the dosage of 1.5,3,and 6 mg/kg,respectively. The results showed that anti-inflammatory activities and analgesic effects of brucine encapsulated were significantly higher than that of the free brucine (P<0.01). Moreover,LB maintained a remarkably longer antiinflammatory and analgesic duration. Conclusion:It can be proposed that LB prepared here could represent a safe,effective and promising transdermal formulation for analgesic and anti-inflammatory effects.

  2. Hyaluronan synthase mediates dye translocation across liposomal membranes

    Directory of Open Access Journals (Sweden)

    Medina Andria P


    Full Text Available Abstract Background Hyaluronan (HA is made at the plasma membrane and secreted into the extracellular medium or matrix by phospolipid-dependent hyaluronan synthase (HAS, which is active as a monomer. Since the mechanism by which HA is translocated across membranes is still unresolved, we assessed the presence of an intraprotein pore within HAS by adding purified Streptococcus equisimilis HAS (SeHAS to liposomes preloaded with the fluorophore Cascade Blue (CB. Results CB translocation (efflux was not observed with mock-purified material from empty vector control E. coli membranes, but was induced by SeHAS, purified from membranes, in a time- and dose-dependent manner. CB efflux was eliminated or greatly reduced when purified SeHAS was first treated under conditions that inhibit enzyme activity: heating, oxidization or cysteine modification with N-ethylmaleimide. Reduced CB efflux also occurred with SeHAS K48E or K48F mutants, in which alteration of K48 within membrane domain 2 causes decreased activity and HA product size. The above results used liposomes containing bovine cardiolipin (BCL. An earlier study testing many synthetic lipids found that the best activating lipid for SeHAS is tetraoleoyl cardiolipin (TO-CL and that, in contrast, tetramyristoyl cardiolipin (TM-CL is an inactivating lipid (Weigel et al, J. Biol. Chem. 281, 36542, 2006. Consistent with the effects of these CL species on SeHAS activity, CB efflux was more than 2-fold greater in liposomes made with TO-CL compared to TM-CL. Conclusions The results indicate the presence of an intraprotein pore in HAS and support a model in which HA is translocated to the exterior by HAS itself.

  3. Phosphatidylserine liposomes can be tethered by caldesmon to actin filaments. (United States)

    Makuch, R; Zasada, A; Mabuchi, K; Krauze, K; Wang, C L; Dabrowska, R


    Rotary shadowing electron microscopy revealed that attachment of caldesmon to phosphatidylserine (PS) liposomes was mainly through its C-terminal end. To determine the PS-binding sites of caldesmon, we have made use of synthetic peptides covering the two C-terminal calmodulin binding sites and a recombinant fragment corresponding to the N-terminal end of the C-terminal domain that contains an amphipathic helix. Interactions of these peptides with the PS liposomes were studied by nondenaturing gel electrophoresis and fluorescence spectroscopy. The results showed that both calmodulin-binding sites of caldesmon were able to interact with PS. The affinity (Kd) of PS for these sites was in the range of 1.8-14.3 x 10(-5) M, compared to 0.69 x 10(-5) M for the whole caldesmon molecule. Fragments located outside of calmodulin-binding sites bound PS weakly (3.85 x 10(-4) M) and thus may contain a second class of lipid-binding sites. Binding of PS induced conformational changes in regions other than the C-terminal PS-binding sites, as evidenced by the changes in the susceptibility to proteolytic cleavages. Most significantly, the presence of caldesmon greatly increased binding of PS to F-actin, suggesting that caldesmon may tether PS liposomes to actin filaments. These results raise the possibility that caldesmon-lipid interactions could play a functionally important role in the assembly of contractile filaments near the membranes. Images FIGURE 2 FIGURE 4 FIGURE 6 PMID:9284327

  4. Liposome-based Formulation for Intracellular Delivery of Functional Proteins

    Directory of Open Access Journals (Sweden)

    Benoît Chatin


    Full Text Available The intracellular delivery of biologically active protein represents an important emerging strategy for both fundamental and therapeutic applications. Here, we optimized in vitro delivery of two functional proteins, the β-galactosidase (β-gal enzyme and the anti-cytokeratin8 (K8 antibody, using liposome-based formulation. The guanidinium-cholesterol cationic lipid bis (guanidinium-tren-cholesterol (BGTC (bis (guanidinium-tren-cholesterol combined to the colipid dioleoyl phosphatidylethanolamine (DOPE (dioleoyl phosphatidylethanolamine was shown to efficiently deliver the β-gal intracellularly without compromising its activity. The lipid/protein molar ratio, protein amount, and culture medium were demonstrated to be key parameters affecting delivery efficiency. The protein itself is an essential factor requiring selection of the appropriate cationic lipid as illustrated by low K8 binding activity of the anti-K8 antibody using guanidinium-based liposome. Optimization of various lipids led to the identification of the aminoglycoside lipid dioleyl succinyl paromomycin (DOSP associated with the imidazole-based helper lipid MM27 as a potent delivery system for K8 antibody, achieving delivery in 67% of HeLa cells. Cryo-transmission electron microscopy showed that the structure of supramolecular assemblies BGTC:DOPE/β-gal and DOSP:MM27/K8 were different depending on liposome types and lipid/protein molar ratio. Finally, we observed that K8 treatment with DOSP:MM27/K8 rescues the cyclic adenosine monophosphate (cAMP-dependent chloride efflux in F508del-CFTR expressing cells, providing a new tool for the study of channelopathies.

  5. Mechanics of Biomimetic Liposomes Encapsulating an Actin Shell. (United States)

    Guevorkian, Karine; Manzi, John; Pontani, Léa-Lætitia; Brochard-Wyart, Françoise; Sykes, Cécile


    Cell-shape changes are insured by a thin, dynamic, cortical layer of cytoskeleton underneath the plasma membrane. How this thin cortical structure impacts the mechanical properties of the whole cell is not fully understood. Here, we study the mechanics of liposomes or giant unilamellar vesicles, when a biomimetic actin cortex is grown at the inner layer of the lipid membrane via actin-nucleation-promoting factors. Using a hydrodynamic tube-pulling technique, we show that tube dynamics is clearly affected by the presence of an actin shell anchored to the lipid bilayer. The same force pulls much shorter tubes in the presence of the actin shell compared to bare membranes. However, in both cases, we observe that the dynamics of tube extrusion has two distinct features characteristic of viscoelastic materials: rapid elastic elongation, followed by a slower elongation phase at a constant rate. We interpret the initial elastic regime by an increase of membrane tension due to the loss of lipids into the tube. Tube length is considerably shorter for cortex liposomes at comparable pulling forces, resulting in a higher spring constant. The presence of the actin shell seems to restrict lipid mobility, as is observed in the corral effect in cells. The viscous regime for bare liposomes corresponds to a leakout of the internal liquid at constant membrane tension. The presence of the actin shell leads to a larger friction coefficient. As the tube is pulled from a patchy surface, membrane tension increases locally, leading to a Marangoni flow of lipids. As a conclusion, the presence of an actin shell is revealed by its action that alters membrane mechanics.

  6. Self-assembled liposome-loaded microbubbles: The missing link for safe and efficient ultrasound triggered drug-delivery. (United States)

    Geers, Bart; Lentacker, Ine; Sanders, Niek N; Demeester, Joseph; Meairs, Stephen; De Smedt, Stefaan C


    Liposome-loaded microbubbles have been recently introduced as a promising drug delivery platform for ultrasound guided drug delivery. In this paper we design liposome-loaded (lipid-shelled) microbubbles through the simple self-assembly of the involved compounds in a single step process. We thoroughly characterized the liposome-loading of the microbubbles and evaluated the cell killing efficiency of this material using doxorubicin (DOX) as a model drug. Importantly, we observed that the DOX liposome-loaded microbubbles allowed killing of melanoma cells even at very low doses of DOX. These findings clearly prove the potential of liposome-loaded microbubbles for ultrasound targeted drug delivery to cancer tissues.

  7. Use of enzyme label for quantitative evaluation of liposome adhesion on cell surface: studies with J774 macrophage monolayers. (United States)

    Trubetskoy, V S; Dormeneva, E V; Tsibulsky, V P; Repin, V S; Torchilin, V P


    A method for quantitation of cell surface-bound liposomes utilizing J774 macrophage monolayers is developed. Surface-bound biotinyl-containing and 125I-labeled liposomes were quantified with avidin-peroxidase in an ELISA-like assay. Peroxidase substrate absorbance values were recalculated into the absolute amount of liposomal lipid using a special calibration plot. Total liposome uptake by macrophages was determined following the binding of 125I radioactivity. The approach suggested allows quantitative evaluation of the changes in the content of surface-adhered liposomes during their interaction with cells in vitro.

  8. Directional Self-assembly in Archaerhodopsin-Reconstituted Phospholipid Liposomes

    Institute of Scientific and Technical Information of China (English)

    吴佳; 黄力; 刘坚; 明明; 李庆国; 丁建东


    This paper reports, for the first time, that Archaerhodopsin-4 (AR4) could be reconstituted into phospholipid liposomes by self-assembly. AR4 is a new membrane protein isolated from halobacteria H.sp. xz515 in a salt lake of Tibet, China. This is a bacteriorhodopsin (bR) like protein, function as a light-driven proton pump. Experimental measurements verified that similar to bR, AR not only remains its biological activity in pmteoliposome, but also keeps a preferred orientation in self-assembly.

  9. Aerosol Performance and Stability of Liposomes Containing Ciprofloxacin Nanocrystals. (United States)

    Cipolla, David; Wu, Huiying; Gonda, Igor; Chan, Hak-Kim


    Previously we showed that the release properties of a liposomal ciprofloxacin (CFI) formulation could be attenuated by incorporation of drug nanocrystals within the vesicles. Rather than forming these drug nanocrystals during drug loading, they were created post manufacture simply by freezing and thawing the formulation. The addition of surfactant to CFI, either polysorbate 20 or Brij 30, provided an additional means to modify the release profile or incorporate an immediate-release or 'burst' component as well. The goal of this study was to develop a CFI formulation that retained its nanocrystalline morphology and attenuated release profile after delivery as an inhaled aerosol. Preparations of 12.5 mg/mL CFI containing 90 mg/mL sucrose and 0.1% polysorbate 20 were formulated between pH 4.6 to 5.9, stored frozen, and thawed prior to use. These thawed formulations, before and after mesh nebulization, and after subsequent refrigerated storage for up to 6 weeks, were characterized in terms of liposome structure by cryogenic transmission electron microscopy (cryo-TEM) imaging, vesicle size by dynamic light scattering, pH, drug encapsulation by centrifugation-filtration, and in vitro release (IVR) performance. Within the narrower pH range of 4.9 to 5.3, these 12.5 mg/mL liposomal ciprofloxacin formulations containing 90 mg/mL sucrose and 0.1% polysorbate 20 retained their physicochemical stability for an additional 3 months refrigerated storage post freeze-thaw, were robust to mesh nebulization maintaining their vesicular form containing nanocrystalline drug and an associated slower release profile, and formed respirable aerosols with a mass median aerodynamic diameter (MMAD) of ∼3.9 μm and a geometric standard deviation (GSD) of ∼1.5. This study demonstrates that an attenuated release liposomal ciprofloxacin formulation can be created through incorporation of drug nanocrystals in response to freeze-thaw, and the formulation retains its physicochemical

  10. A Content Incontinent: Report of Liposomal Bupivacaine Induced Fecal Incontinence

    Directory of Open Access Journals (Sweden)

    Emanuel A. Shapera


    Full Text Available Proper surgical management of anal fistula demands sound clinical judgment and extraordinary care to prevent incontinence and adequate postoperative pain control and provide satisfactory resolution to optimize quality of life. Fecal incontinence can be a devastating complication of procedures performed for fistula in ano. We report a unique case in which temporary incontinence (for less than 4 days followed injection of liposomal bupivacaine for postoperative pain control after draining seton placement for fistula in ano. Patients and physicians should be aware as it may be mistaken for a more serious anatomical and permanent cause of fecal incontinence.

  11. Liposomes as Safe Carriers of Drugs and Vaccines, (United States)


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  12. Effective transcutaneous immunization by antigen-loaded flexible liposome in vivo

    Directory of Open Access Journals (Sweden)

    Li N


    Full Text Available Ni Li1, Li-Hua Peng1, Xi Chen1, Shinsaku Nakagawa2, Jian-Qing Gao11Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China; 2Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, JapanBackground: Transcutaneous vaccines have received wide attention due to their easy-to-use, needle-free, noninvasive delivery. However, the novel barrier function of stratum corneum hinders the transport of antigen and adjuvant in transcutaneous immunization. Novel nanoscale delivery systems employing, for example, liposomes and nanoparticles, have been widely investigated to overcome the penetration barrier of stratum corneum for effective transcutaneous immunization.Objective: The objective of this study was to prepare two types of flexible liposomes and determine their efficacies for the transcutaneous delivery of antigen and the subsequent immune response induced in vivo.Methods: Ovalbumin (OVA liposome-based transcutaneous vaccines were prepared using reverse-phase evaporation and film-dispersion methods. Particle sizes and antigen encapsulating efficiency were then evaluated. After application to bare mouse skin, topical sites were examined for the presence of fluorescence-labeled liposome. The efficacy of the transcutaneously delivered OVA-loaded flexible liposome in activating the immune responses was investigated by detecting serum immunoglobulin G levels. The influence of an adjuvant, imiquimod, in the transcutaneous immunization was also tested.Results: Two flexible liposomes with well-encapsulated OVA were successfully prepared by film-dispersion or reverse-phase evaporation methods. The sizes of the prepared flexible liposomes ranged from 200 to 400 nm. In vivo, the fluorescence-labeled liposome was detected in hair-follicle ducts, indicating that the flexible liposome can penetrate the skin barrier through the hair

  13. Encapsulation of a Lactic Acid Bacteria Cell-Free Extract in Liposomes and Use in Cheddar Cheese Ripening

    Directory of Open Access Journals (Sweden)

    Alice Beebyaanda Nongonierma


    Full Text Available A concentrated form of cell free extract (CFE derived from attenuated Lactococcus lactis supsb. lactis 303 CFE was encapsulated in liposomes prepared from two different proliposome preparations (Prolipo Duo and Prolipo S using microfluidization. Entrapment efficiencies of 19.7 % (Prolipo S and 14.0 % (Prolipo Duo were achieved and the preparations mixed in the ratio 4 (Prolipo Duo:1 (Prolipo S. Cheddar cheese trials were undertaken evaluating the performance of CFE entrapped in liposomes, empty liposomes and free CFE in comparison to a control cheese without any CFE or liposomes. Identical volumes of liposome and amounts of CFE were used in triplicate trials. The inclusion of liposomes did not adversely impact on cheese composition water activity, or microbiology. Entrapment of CFE in liposomes reduced loss of CFE to the whey. No significant differences were evident in proteolysis or expressed PepX activity during ripening in comparison to the cheeses containing free CFE, empty liposomes or the control, as the liposomes did not degrade during ripening. This result highlights the potential of liposomes to minimize losses of encapsulated enzymes into the whey during cheese production but also highlights the need to optimize the hydrophobicity, zeta potential, size and composition of the liposomes to maximize their use as vectors for enzyme addition in cheese to augment ripening.

  14. Encapsulation of a Lactic Acid Bacteria Cell-Free Extract in Liposomes and Use in Cheddar Cheese Ripening. (United States)

    Nongonierma, Alice Beebyaanda; Abrlova, Magdalena; Kilcawley, Kieran Noel


    A concentrated form of cell free extract (CFE) derived from attenuated Lactococcus lactis supsb. lactis 303 CFE was encapsulated in liposomes prepared from two different proliposome preparations (Prolipo Duo and Prolipo S) using microfluidization. Entrapment efficiencies of 19.7 % (Prolipo S) and 14.0 % (Prolipo Duo) were achieved and the preparations mixed in the ratio 4 (Prolipo Duo):1 (Prolipo S). Cheddar cheese trials were undertaken evaluating the performance of CFE entrapped in liposomes, empty liposomes and free CFE in comparison to a control cheese without any CFE or liposomes. Identical volumes of liposome and amounts of CFE were used in triplicate trials. The inclusion of liposomes did not adversely impact on cheese composition water activity, or microbiology. Entrapment of CFE in liposomes reduced loss of CFE to the whey. No significant differences were evident in proteolysis or expressed PepX activity during ripening in comparison to the cheeses containing free CFE, empty liposomes or the control, as the liposomes did not degrade during ripening. This result highlights the potential of liposomes to minimize losses of encapsulated enzymes into the whey during cheese production but also highlights the need to optimize the hydrophobicity, zeta potential, size and composition of the liposomes to maximize their use as vectors for enzyme addition in cheese to augment ripening.

  15. Interaction of local and general anaesthetics with liposomal membrane models: a QCM-D and DSC study. (United States)

    Paiva, José Gabriel; Paradiso, Patrizia; Serro, Ana Paula; Fernandes, Anabela; Saramago, Benilde


    The behaviour of four local anaesthetics (lidocaine, levobupivacaine, ropivacaine and tetracaine) and one general anaesthetic (propofol) is compared when interacting with two types of model membranes: supported layers of liposomes and liposomes in solution. Several liposomal compositions were tested: dimyristoylphosphatidylcholine (DMPC), binary mixtures of DMPC with cholesterol (CHOL), and ternary mixtures of dipalmitoylphosphatidylcholine (DPPC), DMPC, and CHOL. A quartz crystal microbalance with dissipation, QCM-D, was used to assess changes in the properties of supported layers of liposomes. The effect of the anaesthetics on the phase behaviour of the liposomes in suspension was determined by differential scanning calorimetry. Both techniques show that all anaesthetics have a fluidizing effect on the model membranes but, apparently, the solid supported liposomes are less affected by the anaesthetics than the liposomes in solution. Although the different anaesthetics were compared at different concentrations, tetracaine and propofol seem to induce the strongest perturbation on the liposome membrane. The resistance of the liposomes to the anaesthetic action was found to increase with the presence of cholesterol, while adding DPPC to the binary mixture DMPC+CHOL does not change its behaviour. The novelty of the present work resides upon three points: (1) the use of supported layers of liposomes as model membranes to study interactions with anaesthetics; (2) application of QCM-D to assess changes of the adsorbed liposomes; (3) a comparison of the effect of local and general anaesthetics interacting with various model membranes in similar experimental conditions.

  16. Targeted and ultrasound-triggered cancer cell injury using perfluorocarbon emulsion-loaded liposomes endowed with cancer cell-targeting and fusogenic capabilities. (United States)

    Ninomiya, Kazuaki; Yamashita, Takahiro; Tanabe, Yamato; Imai, Miki; Takahashi, Kenji; Shimizu, Nobuaki


    This study investigated the targeting and ultrasound-triggered injury of cancer cells using anticancer drug-free liposomes that contained an emulsion of perfluoropentane (ePFC5) and were co-modified with avidin as a targeting ligand for cancer cells and the hemagglutinating virus of Japan (HVJ) envelope to promote liposome fusion with the cells. These liposomes are designated as ePFC5-loaded avidin/HVJ liposomes. ePFC5-loaded liposomes were sensitized to ultrasound irradiation. Liposomes modified with avidin alone (avidin liposomes) showed binding to MCF-7 human breast cancer cells, and liposomes modified with HVJ envelope alone (HVJ liposomes) were found to fuse with MCF-7 cells. The irradiation of MCF-7 cells with 1 MHz ultrasound (30s, 1.2 W/cm(2), duty ratio 30%) combined with ePFC5-loaded avidin/HVJ liposomes resulted in a decrease in cell viability at 1h after irradiation to 43% of that of controls without ultrasound irradiation or liposomes. The cell viability was lower than that of cells treated with ultrasound irradiation with ePFC5-loaded avidin liposomes or ePFC5-loaded HVJ liposomes. This indicates that co-modification of liposome with avidin and HVJ envelope could enhance ultrasound-induced cell injury in the presence of ePFC5-loaded liposomes.

  17. Enhanced Ehrlich tumor inhibition using DOX-NP™ and gold nanoparticles loaded liposomes (United States)

    Mady, M. M.; Al-Shaikh, F. H.; Al-Farhan, F. F.; Aly, A. A.; Al-Mohanna, M. A.; Ghannam, M. M.


    Treatment with doxorubicin (DOX) is a common regime in treating various types of cancer. DOX-NP™ is one of a well established marketed liposomal formulation for DOX. It offers distinct advantages over conventional DOX in reducing the cardiac toxicity and increasing the tolerability and efficacy. Gold nanoparticles (GNPs), a typical biocompatible nanomaterial, have been widely used in biomedical engineering and bioanalytical applications such as biomedical imaging and biosensors. Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with saline, free doxorubicin (DOX) in solution, gold nanoparticles loaded liposomes and commercial liposomal encapsulated doxorubicin (DOX-NP™). The results showed that GNPs loaded liposomes could enhance the antitumor activity of commercial liposomal formulation (DOX-NP™) and displayed significantly decreased systemic toxicity compared with free DOX and commercial liposomal formulation (DOX-NP™) at the equivalent dose. So the combination of GNPs and liposomes is expected to significantly increase the likelihood of cell killing and make it a promising new approach to cancer therapy.

  18. Antimicrobial peptide-modified liposomes for bacteria targeted delivery of temoporfin in photodynamic antimicrobial chemotherapy. (United States)

    Yang, Kewei; Gitter, Burkhard; Rüger, Ronny; Wieland, Gerhard D; Chen, Ming; Liu, Xiangli; Albrecht, Volker; Fahr, Alfred


    Photodynamic antimicrobial chemotherapy (PACT) and antimicrobial peptides (AMPs) are two promising strategies to combat the increasing prevalence of antibiotic-resistant bacteria. To take advantage of these two strategies, we integrated a novel antimicrobial peptide (WLBU2) and a potent generation II photosensitizer (temoporfin) into liposomes by preparing WLBU2-modified liposomes, aiming at bacteria targeted delivery of temoporfin for PACT. WLBU2 was successfully coupled to temoporfin-loaded liposomes using a functional phospholipid. The delivery of temoporfin to bacteria was confirmed by fluorescence microscopy and flow cytometry, thus demonstrating that more temoporfin was delivered to bacteria by WLBU2-modified liposomes than by unmodified liposomes. Consequently, the WLBU2-modified liposomes eradicated all methicillin-resistant Staphylococcus aureus (MRSA) and induced a 3.3 log(10) reduction of Pseudomonas aeruginosa in the in vitro photodynamic inactivation test. These findings demonstrate that the use of AMP-modified liposomes is promising for bacteria-targeted delivery of photosensitizers and for improving the PACT efficiency against both gram-positive and gram-negative bacteria in the local infections.

  19. Mode of formation and structural features of DNA-cationic liposome complexes used for transfection. (United States)

    Gershon, H; Ghirlando, R; Guttman, S B; Minsky, A


    Complexes formed between cationic liposomes and nucleic acids represent a highly efficient vehicle for delivery of DNA and RNA molecules into a large variety of eukaryotic cells. By using fluorescence, gel electrophoresis, and metal-shadowing electron microscopy techniques, the factors that affect the, yet unclear, interactions between DNA and cationic liposomes as well as the structural features of the resulting complexes have been elucidated. A model is suggested according to which cationic liposomes bind initially to DNA molecules to form clusters of aggregated vesicles along the nucleic acids. At a critical liposome density, two processes occur, namely, DNA-induced membrane fusion, indicated by lipid mixing studies, and liposome-induced DNA collapse, pointed out by the marked cooperativity of the encapsulation processes, by their modulations by DNA-condensing agents, and also by their conspicuous independence upon DNA length. The DNA collapse leads to the formation of condensed structures which can be completely encapsulated within the fused lipid bilayers in a fast, highly cooperative process since their exposed surface is substantially smaller than that of extended DNA molecules. The formation of the transfecting DNA-liposome complexes in which the nucleic acids are fully encapsulated within a positively-charged lipid bilayer is proposed, consequently, to be dominated by mutual effects exerted by the DNA and the cationic liposomes, leading to interrelated lipid fusion and DNA collapse.

  20. Topical liposome targeting of dyes, melanins, genes, and proteins selectively to hair follicles. (United States)

    Hoffman, R M


    For therapeutic and cosmetic modification of hair, we have developed a hair-follicle-selective macromolecule and small molecule targeting system with topical application of phosphatidylcholine-based liposomes. Liposome-entrapped melanins, proteins, genes, and small-molecules have been selectively targeted to the hair follicle and hair shafts of mice. Liposomal delivery of these molecules is time dependent. Negligible amounts of delivered molecules enter the dermis, epidermis, or bloodstream thereby demonstrating selective follicle delivery. Naked molecules are trapped in the stratum corneum and are unable to enter the follicle. The potential of the hair-follicle liposome delivery system for therapeutic use for hair disease as well as for cosmesis has been demonstrated in 3-dimensional histoculture of hair-growing skin and mouse in vivo models. Topical liposome selective delivery to hair follicles has demonstrated the ability to color hair with melanin, the delivery of the active lac-Z gene to hair matrix cells and delivery of proteins as well. Liposome-targeting of molecules to hair follicles has also been achieved in human scalp in histoculture. Liposomes thus have high potential in selective hair follicle targeting of large and small molecules, including genes, opening the field of gene therapy and other molecular therapy of the hair process to restore hair growth, physiologically restore or alter hair pigment, and to prevent or accelerate hair loss.

  1. Acoustically-active microbubbles conjugated to liposomes: characterization of a proposed drug delivery vehicle. (United States)

    Kheirolomoom, Azadeh; Dayton, Paul A; Lum, Aaron F H; Little, Erika; Paoli, Eric E; Zheng, Hairong; Ferrara, Katherine W


    A new acoustically-active delivery vehicle was developed by conjugating liposomes and microbubbles, using the high affinity interaction between avidin and biotin. Binding between microbubbles and liposomes, each containing 5% DSPE-PEG2kBiotin, was highly dependent on avidin concentration and observed above an avidin concentration of 10 nM. With an optimized avidin and liposome concentration, we measured and calculated as high as 1000 to 10,000 liposomes with average diameters of 200 and 100 nm, respectively, attached to each microbubble. Replacing avidin with neutravidin resulted in 3-fold higher binding, approaching the calculated saturation level. High-speed photography of this new drug delivery vehicle demonstrated that the liposome-bearing microbubbles oscillate in response to an acoustic pulse in a manner similar to microbubble contrast agents. Additionally, microbubbles carrying liposomes could be spatially concentrated on a monolayer of PC-3 cells at the focal point of ultrasound beam. As a result of cell-vehicle contact, the liposomes fused with the cells and internalization of NBD-cholesterol occurred shortly after incubation at 37 degrees C, with internalization of NBD-cholesterol substantially enhanced in the acoustic focus.

  2. The potential of liposome-encapsulated ciprofloxacin as a tularemia therapy. (United States)

    Hamblin, Karleigh A; Wong, Jonathan P; Blanchard, James D; Atkins, Helen S


    Liposome-encapsulation has been suggested as method to improve the efficacy of ciprofloxacin against the intracellular pathogen, Francisella tularensis. Early work with a prototype formulation, evaluated for use against the F. tularensis live vaccine strain, showed that a single dose of liposomal ciprofloxacin given by the intranasal or inhalational route could provide protection in a mouse model of pneumonic tularemia. Liposomal ciprofloxacin offered better protection than ciprofloxacin given by the same routes. Liposomal ciprofloxacin has been further developed by Aradigm Corporation for Pseudomonas aeruginosa infections in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis. This advanced development formulation is safe, effective and well tolerated in human clinical trials. Further evaluation of the advanced liposomal ciprofloxacin formulation against the highly virulent F. tularensis Schu S4 strain has shown that aerosolized CFI (Ciprofloxacin encapsulated in liposomes for inhalation) provides significantly better protection than oral ciprofloxacin. Thus, liposomal ciprofloxacin is a promising treatment for tularemia and further research with the aim of enabling licensure under the animal rule is warranted.

  3. The use of liposomal anthracycline analogues for childhood malignancies: A systematic review. (United States)

    Sieswerda, E; Kremer, L C M; Caron, H N; van Dalen, E C


    In an effort to prevent or reduce anthracycline-induced cardiotoxicity, liposomal anthracyclines have been developed. The objective of this systematic review was to summarise all available evidence on the benefits and risks of liposomal anthracyclines in children with cancer. We searched databases (MEDLINE (1966-September 2009), EMBASE (1980-September 2009) and CENTRAL (The Cochrane Library, issue 3 2009)), reference lists of relevant articles and ongoing trial databases for relevant studies. Two reviewers independently performed study selection, data extraction and quality assessment of included studies. No randomised controlled trials (RCTs) or controlled clinical trials (CCTs) were found. Fifteen observational studies described the use of liposomal anthracyclines in children with cancer. Most patients had been treated extensively in the past. Some patients developed cardiotoxicity, serious allergic reactions, mucositis, infections, hematotoxicities and/or hepatotoxicity after single agent treatment. However, due to the low quality of the currently available research, it is unclear what the exact risks are. In conclusion, there is no evidence available from RCTs or CCTs about the benefits and risks of liposomal anthracyclines in children with cancer. Limited data from observational studies suggest that children treated with liposomal anthracyclines are at risk for developing cardiotoxicity and other serious toxicities. There is an urgent need for results of well-designed studies which accurately evaluate the benefits and risks of liposomal anthracyclines in children with cancer. Until high quality evidence is available, we recommend monitoring of cardiac function in childhood cancer patients treated with a liposomal anthracycline and awareness of other serious toxicities.


    Directory of Open Access Journals (Sweden)

    M. Hemanth kumar


    Full Text Available Liposomal Encapsulation Technology (LET is the newest delivery method used by medical researchers to transfer drugs that act as healing promoters to the definite body organs. This form of delivery system offers targeted delivery of vital compounds to the body. It has been in existence since the early 70’s. Liposomal Encapsulation Technology is a state of the art method of producing sub-microscopic bubbles called liposomes, which encapsulate various substances. These phospholipids or “liposomes” form a barrier around their contents that is resistant to enzymes in the mouth and stomach, digestive juices, alkaline solutions, bile salts, and intestinal flora, found in the human body as well as free radicals. The contents of the liposomes are therefore shielded from degradation and oxidation. This protective phospholipid shield or barrier remains unharmed until the contents of the liposome are delivered right to the target organ, gland, or system where the contents will be utilized. Natural extracts are generally degraded because of oxidation and other chemical reactions before they delivered to the target site. Our research has shown liposomal encapsulated ayurvedic preparations have shown more stability and also more efficiency when compared to traditional preparations. Size of liposomes were measured around 85-200 nm.

  5. Recent Progress in Liposome Production, Relevance to Drug Delivery and Nanomedicine. (United States)

    Koynova, Rumiana; Tenchov, Boris


    From their discovery half a century ago and the subsequent appreciation of their clinical utility, liposomes currently hold a recognized position in the mainstream of drug delivery systems. Conventional techniques for liposome preparation and size reduction are simple to implement and do not require sophisticated equipment. However, most of them are not easy to scale-up for industrial liposome production. With several liposomal formulations already on the market, and more in final clinical trials, the industrial scale production of liposomes has become reality, and so the range of liposome preparation methods has been extended by a number of techniques which are increasingly attractive, such as microfluidic hydrodynamic focusing, supercritical fluid processing, freeze-drying and spray-drying. Some of these new techniques generally represent advancements of the conventional methods allowing for scale-up, better reproducibility and process control. This review summarizes patents in the last decade offering new techniques for production of liposomes as related to their application in drug delivery.

  6. Plasmon resonant gold-coated liposomes for spectrally coded content release (United States)

    Leung, Sarah J.; Troutman, Timothy S.; Romanowski, Marek


    We have recently introduced liposome-supported plasmon resonant gold nanoshells (Troutman et al., Adv. Mater. 2008, 20, 2604-2608). These plasmon resonant gold-coated liposomes are degradable into components of a size compatible with renal clearance, potentially enabling their use as multifunctional agents in applications in nanomedicine, including imaging, diagnostics, therapy, and drug delivery. The present research demonstrates that laser illumination at the wavelength matching the plasmon resonance band of a gold-coated liposome leads to the rapid release of encapsulated substances, which can include therapeutic and diagnostic agents. Leakage of encapsulated contents is monitored through the release of self-quenched fluorescein, which provides an increase in fluorescence emission upon release. Moreover, the resonant peak of these gold-coated liposomes is spectrally tunable in the near infrared range by varying the concentration of gold deposited on the surface of liposomes. Varying the plasmon resonant wavelengths of gold-coated liposomes can provide a method for spectrally-coding their light-mediated content release, so that the release event is initiated by the specific wavelength of light used to illuminate the liposomes. The development of spectrally-coded release can find applications in controlled delivery of multiple agents to support complex diagnostic tests and therapeutic interventions.

  7. An EPR spin probe study of liposomes from sunflower and soybean phospholipids. (United States)

    Melnyk, Andrii K; Sukhoveev, Olexandr V; Kononets, Lyudmyla A; Khilchevsky, Olexandr M; Shulga, Serhiy M; Kukhar, Valery P; Vovk, Andriy I


    Comparative properties of lecithin-based liposomes prepared from the mixed phospholipids of sunflower seeds, soybean and egg yolk were investigated by electron paramagnetic resonance (EPR) spectroscopy. For these investigations, stable nitroxide radicals, 1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl 5,7-dimethyladamantane-1-carboxylate (DMAC-TEMPO), 5-doxylstearic acid (5-DSA) and 16-doxylstearic acid (16-DSA) were used as spin probes. Binding of the spin probes to the liposome membranes resulted in a substantial increase of the apparent rotational diffusion correlation times. The EPR spectra of the incorporated nitroxides underwent temperature-dependent changes. For every spin probe, values of apparent enthalpy and entropy of activation were calculated from the temperature dependence of rotational diffusion correlation times via Arrhenius equation. In case of DMAC-TEMPO, the data point to differences between the phospholipid bilayer of liposomes derived from sunflower and soy lecithin, and some similarity between the sunflower and egg yolk liposomes. Anisotropic hyperfine interaction constants of DMAC-TEMPO and 16-DSA included in the liposomes have been analyzed and attributed to different micropolarity of the surroundings of the spin probes. The kinetics of EPR signal decay of DMAC-TEMPO in the presence of 2,2'-azobis(2-amidinopropane) suggest the better stability of the sunflower liposomes to lipid peroxidation as compared to the liposomes prepared from soy lecithin.

  8. Coupling of drug containing liposomes to microbubbles improves ultrasound triggered drug delivery in mice. (United States)

    Cool, Steven K; Geers, Bart; Roels, Stefan; Stremersch, Stephan; Vanderperren, Katrien; Saunders, Jimmy H; De Smedt, Stefaan C; Demeester, Joseph; Sanders, Niek N


    Local extravasation and triggered drug delivery by use of ultrasound and microbubbles is a promising strategy to target drugs to their sites of action. In the past we have developed drug loaded microbubbles by coupling drug containing liposomes to the surface of microbubbles. Until now the advantages of this drug loading strategy have only been demonstrated in vitro. Therefore, in this paper, microbubbles with indocyanine green (ICG) containing liposomes at their surface or a mixture of ICG-liposomes and microbubbles was injected intravenously in mice. Immediately after injection the left hind leg was exposed to 1 MHz ultrasound and the ICG deposition was monitored 1, 4 and 7 days post-treatment by in vivo fluorescence imaging. In mice that received the ICG-liposome loaded microbubbles the local ICG deposition was, at each time point, about 2-fold higher than in mice that received ICG-liposomes mixed with microbubbles. We also showed that the perforations in the blood vessels allow the passage of ICG-liposomes up to 5h after microbubble and ultrasound treatment. An increase in tissue temperature to 41°C was observed in all ultrasound treated mice. However, ultrasound tissue heating was excluded to cause the local ICG deposition. We concluded that coupling of drug containing liposomes to microbubbles may increase ultrasound mediated drug delivery in vivo.

  9. Intra-tumor distribution of PEGylated liposome upon repeated injection: No possession by prior dose. (United States)

    Nakamura, Hiroyuki; Abu Lila, Amr S; Nishio, Miho; Tanaka, Masao; Ando, Hidenori; Kiwada, Hiroshi; Ishida, Tatsuhiro


    Liposomes have proven to be a viable means for the delivery of chemotherapeutic agents to solid tumors. However, significant variability has been detected in their intra-tumor accumulation and distribution, resulting in compromised therapeutic outcomes. We recently examined the intra-tumor accumulation and distribution of weekly sequentially administered oxaliplatin (l-OHP)-containing PEGylated liposomes. In that study, the first and second doses of l-OHP-containing PEGylated liposomes were distributed diversely and broadly within tumor tissues, resulting in a potent anti-tumor efficacy. However, little is known about the mechanism underlying such a diverse and broad liposome distribution. Therefore, in the present study, we investigated the influence of dosage interval on the intra-tumor accumulation and distribution of "empty" PEGylated liposomes. Intra-tumor distribution of sequentially administered "empty" PEGylated liposomes was altered in a dosing interval-dependent manner. In addition, the intra-tumor distribution pattern was closely related to the chronological alteration of tumor blood flow as well as vascular permeability in the growing tumor tissue. These results suggest that the sequential administrations of PEGylated liposomes in well-spaced intervals might allow the distribution to different areas and enhance the total bulk accumulation within tumor tissue, resulting in better therapeutic efficacy of the encapsulated payload. This study may provide useful information for a better design of therapeutic regimens involving multiple administrations of nanocarrier drug delivery systems.

  10. Enzymatic degradation of polymer covered SOPC-liposomes in relation to drug delivery

    DEFF Research Database (Denmark)

    Davidsen, Jesper; Vermehren, C.; Frøkjær, S.


    Polyethylenoxide (PEG) covered liposomes are used as lipid-based drug-delivery systems. In comparison to conventional liposomes the polymer-covered liposomes display a long circulation half-life in the blood stream. We investigate the influence of polyethyleneoxide-distearoylphosphatidylethanolam......Polyethylenoxide (PEG) covered liposomes are used as lipid-based drug-delivery systems. In comparison to conventional liposomes the polymer-covered liposomes display a long circulation half-life in the blood stream. We investigate the influence of polyethyleneoxide......-distearoylphosphatidylethanolamine (DSPE-PEG$-750$/) lipopolymer concentration on phospholipase A$-2$/ (PLA$-2$/) catalyzed hydrolysis of liposomes composed of stearoyloleoylphosphatidylcholine (SOPC). The characteristic PLA$-2$/ lag-time was determined by fluorescence and the degree of lipid hydrolysis was followed by HPLC analysis....... Particle size and zeta-potential were measured as a function of DSPE-PEG$-750$/ lipopolymer concentration. A significant decrease in the lag-time, and hence an increase in enzyme activity, was observed with increasing concentrations of the anionic DSPE-PEG$-750$/ lipopolymer lipids. The observed decrease...

  11. Determination of Liposomal Cisplatin by High-Performance Liquid Chromatography and Its Application in Pharmacokinetic Studies (United States)

    Toro-Córdova, Alfonso; Ledezma-Gallegos, Fabricio; Mondragon-Fuentes, Laura; Jurado, Rafael; Medina, Luis A.; Pérez-Rojas, Jazmin M.; Garcia-Lopez, Patricia


    Liposomes have been employed as carriers for antineoplastic drugs to improve delivery. We describe an HPLC–UV method for determining cisplatin levels in liposomal and biological samples, which represents an attractive alternative to the widely used flame atomic absorption spectroscopy. Liposomal cisplatin was extracted from liposomes, plasma and tissue samples by using acetonitrile and separated on a Symmetry C18 column. The mobile phase was a mixture of water, methanol and acetonitrile, and detection was performed at 254 nm. The method was linear in the range of 0.5–10 µg/mL. Using this method, cisplatin concentration was measured in plasma, kidney, liver and tumor at different times post-administration of liposomal cisplatin. This method is proved suitable for measuring the levels of cisplatin encapsulated in a liposomal system, in plasma or tissue samples of experimental animals, after intravenous administration of liposomal cisplatin. Owing to the small plasma volume employed, a complete pharmacokinetic study can be done with a single animal. PMID:27013666

  12. N-trimethyl chitosan-modified liposomes as carriers for oral delivery of salmon calcitonin. (United States)

    Huang, Aiwen; Makhlof, Abdallah; Ping, Qineng; Tozuka, Yuichi; Takeuchi, Hirofumi


    Therapeutic peptide and protein drugs have high specificity and activity in their functions but present challenges in their administration route, requiring development of new delivery systems to improve their bioavailability. The aim of this work was to investigate the role of N-trimethyl chitosan- (TMC-) coated liposomes in the oral administration of calcitonin. TMC with a degree of quaternization around 78% was synthesized and its mucoadhesive properties were examined in vitro using the mucin-particle method, which confirmed that TMC showed mucoadhesion comparable to that of chitosan. TMC-coated liposomes containing calcitonin were prepared and characterized as having a particle size of 262 nm, zeta potential of 35.8 mV and high entrapment efficiency (89.1%). The in vivo evaluation of mucoadhesion was carried out using confocal laser microscopy to observe the residence time and permeation extent after intragastric administration. The results showed that TMC-coated liposomes prolonged the residence time and increased the penetration effect of the liposomal system compared to non-coated liposomes. The study of pharmacological effects confirmed that TMC-coated liposomes increased the area above the blood calcium concentration-time curves (AAC) from 3.13 ± 20.50 to 448.84 ± 103.56 compared to the calcitonin solution. These results support the feasibility of TMC-coated liposomes as a new oral delivery system for peptide and protein drugs.

  13. Cationic Lipid Content in Liposome-Encapsulated Nisin Improves Sustainable Bactericidal Activity against Streptococcus mutans (United States)

    Yamakami, Kazuo; Tsumori, Hideaki; Shimizu, Yoshitaka; Sakurai, Yutaka; Nagatoshi, Kohei; Sonomoto, Kenji


    An oral infectious disease, dental caries, is caused by the cariogenic streptococci Streptococcus mutans. The expected preventive efficiency for prophylactics against dental caries is not yet completely observed. Nisin, a bacteriocin, has been demonstrated to be microbicidal against S. mutans, and liposome-encapsulated nisin improves preventive features that may be exploited for human oral health. Here we examined the bactericidal effect of charged lipids on nisin-loaded liposomes against S. mutans and inhibitory efficiency for insoluble glucan synthesis by the streptococci for prevention of dental caries. Cationic liposome, nisin-loaded dipalmitoylphosphatidylcholine/phytosphingosine, exhibited higher bactericidal activities than those of electroneutral liposome and anionic liposome. Bactericidal efficiency of the cationic liposome revealed that the vesicles exhibited sustained inhibition of glucan synthesis and the lowest rate of release of nisin from the vesicles. The optimizing ability of cationic liposome-encapsulated nisin that exploit the sustained preventive features of an anti-streptococcal strategy may improve prevention of dental caries. PMID:27583045

  14. Preparation and characterization of cosmeceutical liposomes loaded with avobenzone and arbutin. (United States)

    Liu, Jun-Jen; Nazzal, Sami; Chang, Tzu-Shan; Tsai, Tsuimin


    The objective of this study was to develop and characterize a liposome delivery system coencapsulating two cosmeceutical ingredients, avobenzone (AVO) and arbutin (AR). Two different liposome preparation methods, that is, thin film hydration and reverse-phase evaporation, were evaluated. To obtain the optimal formulation, various ratios of lipid to AVO or AR were tested. The effects of liposome formulation and preparation method on particle size, entrapment efficiency (EE), and skin permeation rate were studied. The mean particle size of the liposome formulations obtained by the thin film hydration method was smaller than that obtained by the reverse-phase evaporation method. The EE of AR and AVO in liposomes prepared by the thin film method, however, was lower than that prepared by the reverse-phase evaporation method. No differences in membrane permeation were observed between the two preparation methods. A large portion of AR permeated through the membrane into the receptor chamber. On the other hand, AVO remained in the donor chamber or accumulated in the membrane. The results of this study revealed that liposomes are a promising delivery system for coencapsulated AR and AVO. Liposomes may aid in retaining the sunscreen (AVO) at the surface of the skin for sun protection meanwhile facilitating the penetration of the whitening agent (AR) into the deeper layers of the skin for whitening effect.

  15. RGD-targeted paramagnetic liposomes for early detection of tumor: In vitro and in vivo studies

    Energy Technology Data Exchange (ETDEWEB)

    Li Wei; Su Bo; Meng Shuyan; Ju Lixia; Yan Linghua; Ding Yongmei; Song Yin; Zhou Wei; Li Heyan; Tang Liang; Zhao Yinmin [Research Institute of Oncology, Tongji University Medical School, 507 Zhenmin Road, Shanghai 200433 (China); Zhou Caicun, E-mail: [Research Institute of Oncology, Tongji University Medical School, 507 Zhenmin Road, Shanghai 200433 (China)


    Magnetic resonance molecular imaging has emerged as a potential approach for tumor diagnosis in the last few decades. This approach consists of the delivery of MR contrast agents to the tumor by specific targeted carriers. For this purpose, a lipopeptide was constructed by using a cyclic RGD peptide headgroup coupled to palmitic acid anchors via a KGG tripeptide spacer. Targeted paramagnetic liposomes were then prepared by the incorporation of RGD-coupled-lipopeptides into lipid bilayers for specific bounding to tumor. In vitro, study demonstrated that RGD-targeted liposomes exhibited a better binding affinity to targeted cells than non-targeted liposomes. MR imaging of mice bearing A549 tumors with the RGD-targeted paramagnetic liposomes also resulted in a greater signal enhancement of tumor compared to non-targeted liposomes and pure contrast agents groups. In addition, biodistribution study also showed specific tumor targeting of RGD-targeted paramagnetic liposomes in vivo. Therefore, RGD-targeted paramagnetic liposomes prepared in the present study may be a more promising method for early tumor diagnosis.

  16. The effect of monosialylganglioside mix modifying the PEGylated liposomal epirubicin on the accelerated blood clearance phenomenon

    Directory of Open Access Journals (Sweden)

    Ting Zhang


    Full Text Available PEGylated liposomes are potential candidates to improve the pharmacokinetic characteristics of encapsulated drugs, to extend their circulation half-life and facilitate their passive accumulation at tumour sites. However, PEG-modified liposomes can induce accelerated blood clearance (ABC upon repeated administration, and the extent of ABC phenomenon on the cytotoxic drugs-containing PEGylated liposomes is related to the dose of the cytotoxic drugs. In this study, EPI served as a model cytotoxic drug, a hydrophilic surfactant molecule, monosialylganglioside (GM1 was chosen and modified on the liposomes together with PEG. It was shown that upon mixed modification, when GM1 contents reached 10% or 15% mol, the ABC phenomenon of the PEGylated liposomal EPI significantly reduced. We also found that GM1 played an important role in abrogating the ABC phenomenon in both the induction phase and the effectuation phase. The results suggested that GM1 incorporation unfortunately did not avoid occurrence of ABC phenomenon completely, but GM1 modification on PEGylated liposomes may provide a significant improvement in clinical practice of PEGylated liposomes. Further study must be necessary.

  17. Current Status of Ethosomes and Elastic Liposomes in Dermal and Transdermal Drug Delivery. (United States)

    Ita, Kevin


    It is still not clear whether intact lipid vesicles can cross the human skin. Some reports in the literature indicate that transfersomes® can cross the skin. Other reports suggest that intact liposomes cannot cross the skin. Of course, the composition of the various formulations has to be taken into consideration before making such assertions. The present review examines the use of vesicles- elastic liposomes and ethosomes- for transdermal drug delivery. Liposomes are micro- or nano-structures formed from a bilayer of lipid surrounding an aqueous core. Elastic liposomes differ from conventional liposomes because they contain edge activators (surfactants) which impart elasticity and deformability. Ethosomes are efficient in facilitating percutaneous drug penetration. They are structurally similar to conventional liposomes in the sense that they are prepared from phospholipids but different because they contain a high concentration of ethanol. Both elastic liposomes and ethosomes are increasingly being used for delivering low and high molecular weight drugs. In this review, several reports are presented showing the usefulness of these vesicles and mechanistic insight sought as to why they may be effective in certain cases.

  18. Massage-induced release of subcutaneously injected liposome-encapsulated drugs to the blood. (United States)

    Trubetskoy, V S; Whiteman, K R; Torchilin, V P; Wolf, G L


    Liposome-based, externally regulated drug delivery system is described in which liposome-encapsulated bioactive molecules can be delivered into the blood in response to simple mechanical action. Without any mechanical stimulation, subcutaneously injected 200 mm liposomes are usually trapped in the interstitial for prolonged time. However, upon lymphotropic stimulation (such as manual massage of the injection site), the liposomes can be mobilized into the blood via lymphatic pathway. Up to 40% of the injection dose can be delivered to the blood via lymphatic pathway from the injection site at the rabbit's front paw dorsum during 5 min manual massage cycle. Using vasoconstricting hormone angiotensin II as liposome-encapsulated pharmacological marker, we demonstrated that physiological response to encapsulated drug (average blood pressure increase) can also induced and modulated by massage. Massage itself was found to have no effect on the blood pressure. Modification of liposome surface with polyethylene glycol was found to increase blood localization of the liposome-encapsulated drug presumably due to decreasing the uptake of the drug carrier by lymph node macrophages. Pressure-dependent gaps between lymphatic capillary endothelial cells are thought to play the role of the size discrimination device allowing larger particulates into the lymphatics and, eventually into the blood after increase of interstitial pressure caused by injection site massage.

  19. Real-time imaging and quantification of brain delivery of liposomes. (United States)

    Krauze, Michal T; Forsayeth, John; Park, John W; Bankiewicz, Krystof S


    The surgical delivery of therapeutic agents into the parenchyma of the brain is problematic because it has been virtually impossible to know with any certainty where infused material is going, and how much to infuse. We have started to use liposomes loaded with Gadoteridol (GDL) as a tracer that allows us to follow infusions in real-time on magnetic resonance imaging (MRI). MRI allows precise tracking and measurement of liposomes loaded with markers and therapeutics. This review provides an overview of real-time delivery of liposomes to the central nervous system (CNS), and discusses the technical aspects of delivery, liposomes as colloidal systems of delivery, real-time distribution of liposomes in CNS, and quantification of liposome distribution. Our data suggests that real-time monitoring of liposomal drug infusion is likely to improve outcomes of clinical trials where convection-enhanced delivery (CED) is being used to target drugs to specific brain structures through limitation of systemic toxicity and reduction of side effects. This review is a summary of work done by our group over the past four years.

  20. Development of a DNA-liposome complex for gene delivery applications. (United States)

    Rasoulianboroujeni, M; Kupgan, G; Moghadam, F; Tahriri, M; Boughdachi, A; Khoshkenar, P; Ambrose, J J; Kiaie, N; Vashaee, D; Ramsey, J D; Tayebi, L


    The association structures formed by cationic liposomes and DNA (Deoxyribonucleic acid)-liposome have been effectively utilized as gene carriers in transfection assays. In this research study, cationic liposomes were prepared using a modified lipid film hydration method consisting of a lyophilization step for gene delivery applications. The obtained results demonstrated that the mean particle size had no significant change while the polydispersity (PDI) increased after lyophilization. The mean particle size slightly reduced after lyophilization (520±12nm to 464±25nm) while the PDI increased after lyophilization (0.094±0.017 to 0.220±0.004). In addition. The mean particle size of vesicles increases when DNA is incorporated to the liposomes (673±27nm). According to the Scanning Electron Microscopy (SEM) and transmission electron microscopy (TEM) images, the spherical shape of liposomes confirmed their successful preservation and reconstitution from the powder. It was found that liposomal formulation has enhanced transfection considerably compared to the naked DNA as negative control. Finally, liposomal formulation in this research had a better function than Lipofectamine® 2000 as a commercialized product because the cellular activity (cellular protein) was higher in the prepared lipoplex than Lipofectamine® 2000. Copyright © 2017 Elsevier B.V. All rights reserved.