Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis.

Science.gov (United States)

Huang, Cuiyuan; Zhang, Hong; Bai, Ruidan

2017-07-01

Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble-mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis

Directory of Open Access Journals (Sweden)

Cuiyuan Huang

2017-07-01

Full Text Available Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble–mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

Transdermal deferoxamine prevents pressure-induced diabetic ulcers

Science.gov (United States)

Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W.; Maan, Zeshaan N.; Rennert, Robert C.; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V.; Whitmore, Arnetha J.; Galvez, Michael G.; Whittam, Alexander J.; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C.

2015-01-01

There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation. PMID:25535360

Microneedle-mediated transdermal delivery of nanostructured lipid carriers for alkaloids from Aconitum sinomontanum.

Science.gov (United States)

Guo, Teng; Zhang, Yongtai; Li, Zhe; Zhao, Jihui; Feng, Nianping

2017-09-12

A combination method using microneedle (MN) pretreatment and nanostructured lipid carriers (NLCs) was developed to improve the transdermal delivery of therapeutics. The MN treatment of the skin and co-administration of NLCs loaded with total alkaloids isolated from Aconitum sinomontanum (AAS-NLCs) significantly increased the skin permeation of the drugs. Fluorescence imaging confirmed that MNs could provide microchannels penetrating the stratum corneum, and delivery of NLCs through the channels led to their deeper permeation. In vivo studies showed that combination of AAS-NLCs with MNs (AAS-NLCs-MN) in transdermal delivery could improve the bioavailability and maintain stable drug concentrations in the blood. Moreover, AAS-NLCs-MN showed benefits in eliminating paw swelling, decreasing inflammation and pain, and regulating immune function in adjuvant arthritis rats. After administration of AAS-NLCs-MN, no skin irritation was observed in rabbits, and electrocardiograms of rats showed improved arrhythmia. These results indicated that the dual approach combining MN insertion and NLCs has the potential to provide safe transdermal delivery and to improve the therapeutic efficacy through sustained release of AAS.

Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs

Science.gov (United States)

Schoellhammer, Carl M.; Srinivasan, Sharanya; Barman, Ross; Mo, Stacy H.; Polat, Baris E.; Langer, Robert; Blankschtein, Daniel

2016-01-01

Low-frequency ultrasound presents an attractive method for transdermal drug delivery. The controlled, yet nonspecific nature of enhancement broadens the range of therapeutics that can be delivered, while minimizing necessary reformulation efforts for differing compounds. Long and inconsistent treatment times, however, have partially limited the attractiveness of this method. Building on recent advances made in this area, the simultaneous use of low- and high-frequency ultrasound is explored in a physiologically relevant experimental setup to enable the translation of this treatment to testing in vivo. Dual-frequency ultrasound, utilizing 20 kHz and 1 MHz wavelengths simultaneously, was found to significantly enhance the size of localized transport regions (LTRs) in both in vitro and in vivo models while decreasing the necessary treatment time compared to 20 kHz alone. Additionally, LTRs generated by treatment with 20 kHz + 1 MHz were found to be more permeable than those generated with 20 kHz alone. This was further corroborated with pore-size estimates utilizing hindered-transport theory, in which the pores in skin treated with 20 kHz + 1 MHz were calculated to be significantly larger than the pores in skin treated with 20 kHz alone. This demonstrates for the first time that LTRs generated with 20 kHz + 1 MHz are also more permeable than those generated with 20 kHz alone, which could broaden the range of therapeutics and doses administered transdermally. With regard to safety, treatment with 20 kHz + 1 MHz both in vitro and in vivo appeared to result in no greater skin disruption than that observed in skin treated with 20 kHz alone, an FDA-approved modality. This study demonstrates that dual-frequency ultrasound is more efficient and effective than single-frequency ultrasound and is well-tolerated in vivo. PMID:25662228

Granisetron Transdermal Patch

Science.gov (United States)

Granisetron transdermal patches are used to prevent nausea and vomiting caused by chemotherapy. Granisetron is in a class of medications called 5HT3 ... Granisetron transdermal comes as a patch to apply to the skin. It is usually applied 24 to ...

TRANSDERMAL DRUG DELIVERY SYSTEM: REVIEW

OpenAIRE

Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma

2012-01-01

Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...

In vivo real-time monitoring system of electroporation mediated control of transdermal and topical drug delivery.

Science.gov (United States)

Blagus, Tanja; Markelc, Bostjan; Cemazar, Maja; Kosjek, Tina; Preat, Veronique; Miklavcic, Damijan; Sersa, Gregor

2013-12-28

Electroporation (EP) is a physical method for the delivery of molecules into cells and tissues, including the skin. In this study, in order to control the degree of transdermal and topical drug delivery, EP at different amplitudes of electric pulses was evaluated. A new in vivo real-time monitoring system based on fluorescently labeled molecules was developed, for the quantification of transdermal and topical drug delivery. EP of the mouse skin was performed with new non-invasive multi-array electrodes, delivering different amplitudes of electric pulses ranging from 70 to 570 V, between the electrode pin pairs. Patches, soaked with 4 kDa fluorescein-isothiocyanate labeled dextran (FD), doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after EP. The new monitoring system was developed based on the delivery of FD to and through the skin. FD relative quantity was determined with fluorescence microscopy imaging, in the treated region of the skin for topical delivery and in a segment of the mouse tail for transdermal delivery. The application of electric pulses for FD delivery resulted in enhanced transdermal delivery. Depending on the amplitude of electric pulses, it increased up to the amplitude of 360 V, and decreased at higher amplitudes (460 and 570 V). Topical delivery steadily enhanced with increasing the amplitude of the delivered electric pulses, being even higher than after tape stripping used as a positive control. The non-invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug, qualitatively and quantitatively confirmed the effects of EP at 360 and 570 V pulse amplitudes on topical and transdermal drug delivery. Delivery of FEN at 360 and 570 V pulse amplitudes verified the observed effects as obtained with FD and DOX, by the measured physiological responses of the mice as well as FEN plasma concentration. This study demonstrates that with the newly developed non-invasive multi-array electrodes and with the

Ultrasound-mediated vascular gene transfection by cavitation of endothelial-targeted cationic microbubbles.

Science.gov (United States)

Xie, Aris; Belcik, Todd; Qi, Yue; Morgan, Terry K; Champaneri, Shivam A; Taylor, Sarah; Davidson, Brian P; Zhao, Yan; Klibanov, Alexander L; Kuliszewski, Michael A; Leong-Poi, Howard; Ammi, Azzdine; Lindner, Jonathan R

2012-12-01

Ultrasound-mediated gene delivery can be amplified by acoustic disruption of microbubble carriers that undergo cavitation. We hypothesized that endothelial targeting of microbubbles bearing cDNA is feasible and, through optimizing proximity to the vessel wall, increases the efficacy of gene transfection. Contrast ultrasound-mediated gene delivery is a promising approach for site-specific gene therapy, although there are concerns with the reproducibility of this technique and the safety when using high-power ultrasound. Cationic lipid-shelled decafluorobutane microbubbles bearing a targeting moiety were prepared and compared with nontargeted microbubbles. Microbubble targeting efficiency to endothelial adhesion molecules (P-selectin or intercellular adhesion molecule [ICAM]-1) was tested using in vitro flow chamber studies, intravital microscopy of tumor necrosis factor-alpha (TNF-α)-stimulated murine cremaster muscle, and targeted contrast ultrasound imaging of P-selectin in a model of murine limb ischemia. Ultrasound-mediated transfection of luciferase reporter plasmid charge coupled to microbubbles in the post-ischemic hindlimb muscle was assessed by in vivo optical imaging. Charge coupling of cDNA to the microbubble surface was not influenced by the presence of targeting ligand, and did not alter the cavitation properties of cationic microbubbles. In flow chamber studies, surface conjugation of cDNA did not affect attachment of targeted microbubbles at microvascular shear stresses (0.6 and 1.5 dyne/cm(2)). Attachment in vivo was also not affected by cDNA according to intravital microscopy observations of venular adhesion of ICAM-1-targeted microbubbles and by ultrasound molecular imaging of P-selectin-targeted microbubbles in the post-ischemic hindlimb in mice. Transfection at the site of high acoustic pressures (1.0 and 1.8 MPa) was similar for control and P-selectin-targeted microbubbles but was associated with vascular rupture and hemorrhage. At 0.6 MPa

Ultrasound-mediated drug delivery using liposomes modified with a thermosensitive polymer.

Science.gov (United States)

Ninomiya, Kazuaki; Kawabata, Shinya; Tashita, Hiroyuki; Shimizu, Nobuaki

2014-01-01

Ultrasound-mediated drug delivery was established using liposomes that were modified with the thermosensitive polymer (TSP) poly(NIPMAM-co-NIPAM), which sensitized the liposomes to high temperatures. TSP-modified liposomes (TSP liposomes) released encapsulated calcein under 1 MHz ultrasound irradiation at 0.5 W/cm(2) for 120 s as well as the case under incubation at 42 °C for 15 min. In addition, uptake of the drug released from TSP liposomes by cancer cells was enhanced by ultrasound irradiation. In a cell injury assay using doxorubicin (DOX)-loaded TSP liposomes and ultrasound irradiation, cell viability of HepG2 cells at 6 h after ultrasound irradiation (1 MHz, 0.5 W/cm(2) for 30 s) with DOX-loaded TSP liposomes (TSP/lipid ratio=1) was 60%, which was significantly lower than that of the control conditions such as DOX-loaded TSP liposomes alone and DOX-loaded intact liposomes under ultrasound irradiation. Copyright © 2013 Elsevier B.V. All rights reserved.

PLGA Nanoparticles for Ultrasound-Mediated Gene Delivery to Solid Tumors

Directory of Open Access Journals (Sweden)

Marxa Figueiredo

2012-01-01

Full Text Available This paper focuses on novel approaches in the field of nanotechnology-based carriers utilizing ultrasound stimuli as a means to spatially target gene delivery in vivo, using nanoparticles made with either poly(lactic-co-glycolic acid (PLGA or other polymers. We specifically discuss the potential for gene delivery by particles that are echogenic (amenable to destruction by ultrasound composed either of polymers (PLGA, polystyrene or other contrast agent materials (Optison, SonoVue microbubbles. The use of ultrasound is an efficient tool to further enhance gene delivery by PLGA or other echogenic particles in vivo. Echogenic PLGA nanoparticles are an attractive strategy for ultrasound-mediated gene delivery since this polymer is currently approved by the US Food and Drug Administration for drug delivery and diagnostics in cancer, cardiovascular disease, and also other applications such as vaccines and tissue engineering. This paper will review recent successes and the potential of applying PLGA nanoparticles for gene delivery, which include (a echogenic PLGA used with ultrasound to enhance local gene delivery in tumors or muscle and (b PLGA nanoparticles currently under development, which could benefit in the future from ultrasound-enhanced tumor targeted gene delivery.

Ultrasound-microbubble mediated cavitation of plant cells: effects on morphology and viability.

Science.gov (United States)

Qin, Peng; Xu, Lin; Zhong, Wenjing; Yu, Alfred C H

2012-06-01

The interaction between ultrasound pulses and microbubbles is known to generate acoustic cavitation that may puncture biological cells. This work presents new experimental findings on the bioeffects of ultrasound-microbubble mediated cavitation in plant cells with emphasis on direct observations of morphological impact and analysis of viability trends in tobacco BY-2 cells that are widely studied in higher plant physiology. The tobacco cell suspensions were exposed to 1 MHz ultrasound pulses in the presence of 1% v/v microbubbles (10% duty cycle; 1 kHz pulse repetition frequency; 70 mm between probe and cells; 1-min exposure time). Few bioeffects were observed at low peak negative pressures (cavitation presumably occurred. In contrast, at 0.9 MPa peak negative pressure (with more inertial cavitation activities according to our passive cavitation detection results), random pores were found on tobacco cell wall (observed via scanning electron microscopy) and enhanced exogenous uptake into the cytoplasm was evident (noted in our fluorescein isothiocyanate dextran uptake analysis). Also, instant lysis was observed in 23.4% of cells (found using trypan blue staining) and programmed cell death was seen in 23.3% of population after 12 h (determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling [TUNEL]). These bioeffects generally correspond in trend with those for mammalian cells. This raises the possibility of developing ultrasound-microbubble mediated cavitation into a targeted gene transfection paradigm for plant cells and, conversely, adopting plant cells as experimental test-beds for sonoporation-based gene therapy in mammalian cells. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Transdermal granisetron.

Science.gov (United States)

Duggan, Sean T; Curran, Monique P

2009-01-01

Granisetron is a highly selective serotonin 5-HT(3) receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. The transdermal granisetron system delivers continuous granisetron (3.1 mg/day) into the systemic circulation (via passive diffusion) for up to 7 days. In a large phase III trial in cancer patients receiving multi-day (3-5 days) moderately or highly emetogenic chemotherapy, transdermal granisetron applied 24-48 hours prior to chemotherapy and remaining in place for 7 days was noninferior to oral granisetron 2 mg once daily administered for 3-5 days 1 hour prior to chemotherapy. Efficacy was assessed according to the proportion of patients achieving complete response (no vomiting and/or retching, no more than mild nausea, no rescue medication) from the first day, until 24 hours after the start of the last day, of administration of the chemotherapy regimen. In a phase II trial in patients with cancer receiving single-day, moderately-emetogenic chemotherapy, transdermal granisetron applied at least 24 hours prior to chemotherapy and removed after 5 days was as effective as a single oral dose of granisetron 2 mg in achieving total control (no nausea, no vomiting/retching, no use of rescue medication and no study withdrawal) during the delayed (24-120 hours; primary endpoint) period after chemotherapy. Transdermal granisetron was generally well tolerated in clinical trials, with few adverse events being treatment related.

Challenges and opportunities in dermal/transdermal delivery

Science.gov (United States)

Paudel, Kalpana S; Milewski, Mikolaj; Swadley, Courtney L; Brogden, Nicole K; Ghosh, Priyanka; Stinchcomb, Audra L

2010-01-01

Transdermal drug delivery is an exciting and challenging area. There are numerous transdermal delivery systems currently available on the market. However, the transdermal market still remains limited to a narrow range of drugs. Further advances in transdermal delivery depend on the ability to overcome the challenges faced regarding the permeation and skin irritation of the drug molecules. Emergence of novel techniques for skin permeation enhancement and development of methods to lessen skin irritation would widen the transdermal market for hydrophilic compounds, macromolecules and conventional drugs for new therapeutic indications. As evident from the ongoing clinical trials of a wide variety of drugs for various clinical conditions, there is a great future for transdermal delivery of drugs. PMID:21132122

Myth or Reality-Transdermal Magnesium?

Science.gov (United States)

Gröber, Uwe; Werner, Tanja; Vormann, Jürgen; Kisters, Klaus

2017-07-28

In the following review, we evaluated the current literature and evidence-based data on transdermal magnesium application and show that the propagation of transdermal magnesium is scientifically unsupported. The importance of magnesium and the positive effects of magnesium supplementation are extensively documented in magnesium deficiency, e.g., cardiovascular disease and diabetes mellitus. The effectiveness of oral magnesium supplementation for the treatment of magnesium deficiency has been studied in detail. However, the proven and well-documented oral magnesium supplementation has become questioned in the recent years through intensive marketing for its transdermal application (e.g., magnesium-containing sprays, magnesium flakes, and magnesium salt baths). In both, specialist and lay press as well as on the internet, there are increasing numbers of articles claiming the effectiveness and superiority of transdermal magnesium over an oral application. It is claimed that the transdermal absorption of magnesium in comparison to oral application is more effective due to better absorption and fewer side effects as it bypasses the gastrointestinal tract.

Alghedon Fentanyl Transdermal System.

Science.gov (United States)

Romualdi, Patrizia; Santi, Patrizia; Candeletti, Sanzio

2017-04-01

The efficacy of transdermal fentanyl for cancer pain and chronic non-cancer pain (chronic lower back pain, rheumatoid arthritis, osteoarthritis, neuropathic pain) is well established. Several formulations of fentanyl transdermal systems have been developed to improve the drug delivery and prevent misuse of the active principle. The addition of a rate controlling membrane to the matrix system represented an important advance. The design and functional features of Alghedon patch are compared with other approved generic fentanyl transdermal systems, emphasizing the distinctiveness of Alghedon patch. Alghedon patch has no liquid component in the finished product, therefore no leakage of active ingredient from the system can occur. A rate-controlling membrane provides controlled release of the active substance from the matrix reservoir, ensuring that fentanyl delivery and entry into the microcirculation is not solely controlled by the skin's permeability to this active substance. Alghedon patch contains part of the drug (approximately 15%) in the skin-contact adhesive: this innovative solution allows to overcome a typical drawback of transdermal patches, i.e. the long lag-time before the drug appears in plasma after the first administration, and provides rapid analgesia during the first hours of administration. Alghedon Fentanyl Transdermal System employs materials commonly used in other transdermal applications and having established safety profiles. For each strength level, the fentanyl content - and, thus, the resulting residual fentanyl remaining in the patch after use - is at the lowest end of the range used in commercially available fentanyl patches, minimizing the potential for abuse and misuse.

Transdermal patches: history, development and pharmacology

Science.gov (United States)

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-01-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. PMID:25560046

Challenges and opportunities in dermal/transdermal delivery

OpenAIRE

Paudel, Kalpana S; Milewski, Mikolaj; Swadley, Courtney L; Brogden, Nicole K; Ghosh, Priyanka; Stinchcomb, Audra L

2010-01-01

Transdermal drug delivery is an exciting and challenging area. There are numerous transdermal delivery systems currently available on the market. However, the transdermal market still remains limited to a narrow range of drugs. Further advances in transdermal delivery depend on the ability to overcome the challenges faced regarding the permeation and skin irritation of the drug molecules. Emergence of novel techniques for skin permeation enhancement and development of methods to lessen skin i...

Effects of ultrasound and sodium lauryl sulfate on the transdermal delivery of hydrophilic permeants: Comparative in vitro studies with full-thickness and split-thickness pig and human skin.

Science.gov (United States)

Seto, Jennifer E; Polat, Baris E; Lopez, Renata F V; Blankschtein, Daniel; Langer, Robert

2010-07-01

The simultaneous application of ultrasound and the surfactant sodium lauryl sulfate (referred to as US/SLS) to skin enhances transdermal drug delivery (TDD) in a synergistic mechanical and chemical manner. Since full-thickness skin (FTS) and split-thickness skin (STS) differ in mechanical strength, US/SLS treatment may have different effects on their transdermal transport pathways. Therefore, we evaluated STS as an alternative to the well-established US/SLS-treated FTS model for TDD studies of hydrophilic permeants. We utilized the aqueous porous pathway model to compare the effects of US/SLS treatment on the skin permeability and the pore radius of pig and human FTS and STS over a range of skin electrical resistivity values. Our findings indicate that the US/SLS-treated pig skin models exhibit similar permeabilities and pore radii, but the human skin models do not. Furthermore, the US/SLS-enhanced delivery of gold nanoparticles and quantum dots (two model hydrophilic macromolecules) is greater through pig STS than through pig FTS, due to the presence of less dermis that acts as an artificial barrier to macromolecules. In spite of greater variability in correlations between STS permeability and resistivity, our findings strongly suggest the use of 700microm-thick pig STS to investigate the in vitro US/SLS-enhanced delivery of hydrophilic macromolecules. 2010 Elsevier B.V. All rights reserved.

Spray-on transdermal drug delivery systems.

Science.gov (United States)

Ibrahim, Sarah A

2015-02-01

Transdermal drug delivery possesses superior advantages over other routes of administration, particularly minimizing first-pass metabolism. Transdermal drug delivery is challenged by the barrier nature of skin. Numerous technologies have been developed to overcome the relatively low skin permeability, including spray-on transdermal systems. A transdermal spray-on system (TSS) usually consists of a solution containing the drug, a volatile solvent and in many cases a chemical penetration enhancer. TSS promotes drug delivery via the complex interplay between solvent evaporation and drug-solvent drag into skin. The volatile solvent carries the drug into the upper layers of the stratum corneum, and as the volatile solvent evaporates, an increase in the thermodynamic activity of the drug occurs resulting in an increased drug loading in skin. TSS is easily applied, delivering flexible drug dosage and associated with lower incidence of skin irritation. TSS provides a fast-drying product where the volatile solvent enables uniform drug distribution with minimal vehicle deposition on skin. TSS ensures precise dose administration that is aesthetically appealing and eliminates concerns of residual drug associated with transdermal patches. Furthermore, it provides a better alternative to traditional transdermal products due to ease of product development and manufacturing.

Iontophoretic and Microneedle Mediated Transdermal Delivery of Glycopyrrolate

Directory of Open Access Journals (Sweden)

Meera Gujjar

2014-12-01

Full Text Available Purpose: The objective of this study was to investigate the use of iontophoresis, soluble microneedles and their combination for the transdermal delivery of glycopyrrolate. Methods: In vitro permeation was tested using full thickness porcine ear skin mounted onto Franz diffusion cells. Iontophoresis (0.5 mA/cm2 was done for 4 h using Ag/AgCl electrodes. For microneedles, three line array (27 needles/line of maltose microneedles were used to microporate the skin prior to mounting. Pore uniformity was determined by taking fluorescent images of distribution of calcein into pores and processing the images using an image analysis tool, which measured the fluorescent intensity in and around each pore to provide a pore permeability index (PPI. The donor chamber contained 500 µL of a 1 mg/mL solution of glycopyrrolate, and the receptor chamber contained 5 mL of 50 mM NaCl in deionized water. Samples were collected at predetermined time points over a period of 24 h and analyzed by HPLC. Skin irritation testing was performed with a 3D cell culture kit of human skin. MTT assay determined cell viability; viability less than 50% was considered irritant. Results: A control experiment which investigated passive permeation of glycopyrrolate delivered an average cumulative amount of 24.92 ± 1.77 µg/cm2 at 24 h, while microneedle pretreatment increased permeability to 46.54 ± 6.9 µg/cm2. Both iontophoresis (158.53 ± 17.50 µg/cm2 and a combination of iontophoresis and microneedles (182.43 ± 20.06 µg/ cm2 significantly increased delivery compared to passive and microneedles alone. Glycopyrrolate solution was found to be nonirritant with cell viability of 70.4% ± 5.03%. Conclusion: Iontophoresis and a combination of iontophoresis with microneedle pretreatment can be effectively used to enhance the transdermal delivery of glycopyrrolate. Glycopyrrolate was found to be non-irritant to skin.

Microbubble-Mediated Ultrasound Enhances the Lethal Effect of Gentamicin on Planktonic Escherichia coli

Directory of Open Access Journals (Sweden)

Han-Xiao Zhu

2014-01-01

Full Text Available Previous research has found that low-intensity ultrasound enhanced the lethal effect of gentamicin on planktonic E. coli. We aimed to further investigate whether microbubble-mediated low-intensity ultrasound could further enhance the antimicrobial efficacy of gentamicin. The planktonic E. coli (ATCC 25922 was distributed to four different interventions: control (GCON, microbubble only (GMB, ultrasound only (GUS, and microbubble-mediated ultrasound (GMUS. Ultrasound was applied with 100 mW/cm2 (average intensity and 46.5 KHz, which presented no bactericidal activity. After 12 h, plate counting was used to estimate the number of bacteria, and bacterial micromorphology was observed with transmission electron microscope. The results showed that the viable counts of E. coli in GMUS were decreased by 1.01 to 1.42 log10 CFU/mL compared with GUS (P<0.01. The minimal inhibitory concentration (MIC of gentamicin against E. coli was 1 μg/mL in the GMUS and GUS groups, lower than that in the GCON and GMB groups (2 μg/mL. Transmission electron microscopy (TEM images exhibited more destruction and higher thickness of bacterial cell membranes in the GMUS than those in other groups. The reason might be the increased permeability of cell membranes for gentamicin caused by acoustic cavitation.

Ultrasound-mediated drug delivery by gas bubbles generated from a chemical reaction.

Science.gov (United States)

Lee, Sungmun; Al-Kaabi, Leena; Mawart, Aurélie; Khandoker, Ahsan; Alsafar, Habiba; Jelinek, Herbert F; Khalaf, Kinda; Park, Ji-Ho; Kim, Yeu-Chun

2018-02-01

Highly echogenic and ultrasound-responsive microbubbles such as nitrogen and perfluorocarbons have been exploited as ultrasound-mediated drug carriers. Here, we propose an innovative method for drug delivery using microbubbles generated from a chemical reaction. In a novel drug delivery system, luminol encapsulated in folate-conjugated bovine serum albumin nanoparticles (Fol-BSAN) can generate nitrogen gas (N 2 ) by chemical reaction when it reacts with hydrogen peroxide (H 2 O 2 ), one of reactive oxygen species (ROS). ROS plays an important role in the initiation and progression of cancer and elevated ROS have been observed in cancer cells both in vitro and in vivo. High-intensity focussed ultrasound (HIFU) is used to burst the N 2 microbubbles, causing site-specific delivery of anticancer drugs such as methotrexate. In this research, the drug delivery system was optimised by using water-soluble luminol and Mobil Composition of Matter-41 (MCM-41), a mesoporous material, so that the delivery system was sensitive to micromolar concentrations of H 2 O 2 . HIFU increased the drug release from Fol-BSAN by 52.9 ± 2.9% in 10 minutes. The cytotoxicity of methotrexate was enhanced when methotrexate is delivered to MDA-MB-231, a metastatic human breast cancer cell line, using Fol-BSAN with HIFU. We anticipate numerous applications of chemically generated microbubbles for ultrasound-mediated drug delivery.

A multimodal instrument for real-time in situ study of ultrasound and cavitation mediated drug delivery.

Science.gov (United States)

Bian, Shuning; Seth, Anjali; Daly, Dan; Carlisle, Robert; Stride, Eleanor

2017-03-01

The development of a multimodal instrument capable of real-time in situ measurements of cavitation activity and effect in tissue mimicking phantoms during ultrasound and cavitation mediated drug delivery experiments is described here. The instrument features an acoustic arm that can expose phantoms to high-intensity focused-ultrasound while measuring cavitation activity and an optical arm that monitors cavitation effect using confocal microscopy. This combination of modalities allows real-time in situ characterisation of drug delivery in tissue and tissue mimicking phantoms during ultrasound and cavitation mediated drug delivery experiments. A representative result, obtained with a tissue mimicking phantom and acoustically activated droplets, is presented here as a demonstration of the instrument's capabilities and potential applications.

Perspectives on Transdermal Electroporation

Science.gov (United States)

Ita, Kevin

2016-01-01

Transdermal drug delivery offers several advantages, including avoidance of erratic absorption, absence of gastric irritation, painlessness, noninvasiveness, as well as improvement in patient compliance. With this mode of drug administration, there is no pre-systemic metabolism and it is possible to increase drug bioavailability and half-life. However, only a few molecules can be delivered across the skin in therapeutic quantities. This is because of the hindrance provided by the stratum corneum. Several techniques have been developed and used over the last few decades for transdermal drug delivery enhancement. These include sonophoresis, iontophoresis, microneedles, and electroporation. Electroporation, which refers to the temporary perturbation of the skin following the application of high voltage electric pulses, has been used to increase transcutaneous flux values by several research groups. In this review, transdermal electroporation is discussed and the use of the technique for percutaneous transport of low and high molecular weight compounds described. This review also examines our current knowledge regarding the mechanisms of electroporation and safety concerns arising from the use of this transdermal drug delivery technique. Safety considerations are especially important because electroporation utilizes high voltage pulses which may have deleterious effects in some cases. PMID:26999191

Encapsulated Curcumin for Transdermal Administration

African Journals Online (AJOL)

Purpose: To develop a proniosomal carrier system of curcumin for transdermal delivery. Methods: Proniosomes of curcumin were prepared by encapsulation of the drug in a mixture of Span 80, cholesterol and diethyl ether by ether injection method, and then investigated as a transdermal drug delivery system (TDDS).

Ablation of benign prostatic hyperplasia using microbubble-mediated ultrasound cavitation.

Science.gov (United States)

Li, Tao; Liu, Zheng

2010-04-01

Benign prostatic hyperplasia (BPH) is a world-wide common disease in elderly male patients. A number of invasive physiotherapies have been used to replace prostatectomy. In this article we report our hypothesis of using microbubbles-mediated ultrasound cavitation effects to ablate prostatic tissues. Microbubble ultrasound contrast agent is widely used contrast media in ultrasonography, yet it is also found to act as cavitation nuclei or enhancer. Once excited by a high peak pressure ultrasound pulse, the mechanical effects, like shock wave and microstream, released from cavitation could produce a series of bioeffects, contributing to sonoporation, microvascular rupture and hematoma. BPH is known to have hyperplastic neovasculature and this make it possible to be disrupted by the physical effects of cavitation under existing microbubbles in circulation. Mechanical ablation of prostatic capillary or small vessels could result in pathological alterations such as thrombosis, micro-circulation blockage, prostatic necrosis and atrophia. Thereupon it could effectively treat BPH by nontraumatic ways. (c) 2009 Elsevier Ltd. All rights reserved.

Transdermal hyoscine induced unilateral mydriasis.

LENUS (Irish Health Repository)

Hannon, Breffni

2012-03-20

The authors present a case of unilateral mydriasis in a teenager prescribed transdermal hyoscine hydrobromide (scopolamine) for chemotherapy induced nausea and vomiting. The authors discuss the ocular side-effects associated with this particular drug and delivery system and the potential use of transdermal hyoscine as an antiemetic agent in this group.

Dissolving polymeric microneedle arrays for electrically assisted transdermal drug delivery.

Science.gov (United States)

Garland, Martin J; Caffarel-Salvador, Ester; Migalska, Katarzyna; Woolfson, A David; Donnelly, Ryan F

2012-04-10

It has recently been proposed that the combination of skin barrier impairment using microneedles (MNs) coupled with iontophoresis (ITP) may broaden the range of drugs suitable for transdermal delivery, as well as enabling the rate of delivery to be achieved with precise electronic control. However, no reports exist on the combination of ITP with in situ drug loaded polymeric MN delivery systems. Furthermore, although a number of studies have highlighted the importance of MN design for transdermal drug delivery enhancement, to date, there has been no systematic investigation of the influence of MN geometry on the performance of polymeric MN arrays which are designed to remain in contact with the skin during the period of drug delivery. As such, for the first time, this study reports on the effect of MN heigth and MN density upon the transdermal delivery of small hydrophilic compounds (theophylline, methylene blue, and fluorescein sodium) across neonatal porcine skin in vitro, with the optimised MN array design evaluated for its potential in the electrically faciliatated delivery of peptide (bovine insulin) and protein (fluorescein isothiocyanate-labelled bovine serum albumin (FTIC-BSA)) macromolecules. The results of the in vitro drug release investigations revealed that the extent of transdermal delivery was dependent upon the design of the MN array employed, whereby an increase in MN height and an increase in MN density led to an increase in the extent of transdermal drug delivery achieved 6h after MN application. Overall, the in vitro permeation studies revealed that the MN design containing 361 MNs/cm(2) of 600 μm height resulted in the greatest extent of transdermal drug delivery. As such, this design was evaluated for its potential in the MN mediated iontophoretic transdermal delivery. Whilst the combination of MN and ITP did not further enhance the extent of small molecular weight solute delivery, the extent of peptide/protein release was significantly

Ultrasound-Mediated Local Drug and Gene Delivery Using Nanocarriers

Science.gov (United States)

Zhou, Qiu-Lan; Chen, Zhi-Yi; Yang, Feng

2014-01-01

With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers. PMID:25202710

Ultrasound-Mediated Local Drug and Gene Delivery Using Nanocarriers

Directory of Open Access Journals (Sweden)

Qiu-Lan Zhou

2014-01-01

Full Text Available With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo, including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers.

Some Recent Advances in Transdermal Drug Delivery Systems ...

African Journals Online (AJOL)

Some Recent Advances in Transdermal Drug Delivery Systems. ... Advances in Transdermal Drug Delivery Systems. EC Ibezim, B Kabele-Toge, CO Anie, C Njoku. Abstract. Transdermal delivery systems are forms of drug delivery involving the dermis, as distinct from topical, oral or other forms of parenteral dosage forms.

Ultrasound-Mediated Drug/Gene Delivery in Solid Tumor Treatment

Directory of Open Access Journals (Sweden)

Yufeng Zhou

2013-01-01

Full Text Available Ultrasound is an emerging modality for drug delivery in chemotherapy. This paper reviews this novel technology by first introducing the designs and characteristics of three classes of drug/gene vehicles, microbubble (including nanoemulsion, liposomes, and micelles. In comparison to conventional free drug, the targeted drug-release and delivery through vessel wall and interstitial space to cancerous cells can be activated and enhanced under certain sonication conditions. In the acoustic field, there are several reactions of these drug vehicles, including hyperthermia, bubble cavitation, sonoporation, and sonodynamics, whose physical properties are illustrated for better understanding of this approach. In vitro and in vivo results are summarized, and future directions are discussed. Altogether, ultrasound-mediated drug/gene delivery under imaging guidance provides a promising option in cancer treatment with enhanced agent release and site specificity and reduced toxicity.

Permeation enhancer strategies in transdermal drug delivery.

Science.gov (United States)

Marwah, Harneet; Garg, Tarun; Goyal, Amit K; Rath, Goutam

2016-01-01

Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.

Synthesis of conjugated chitosan and its effect on drug permeation from transdermal patches.

Science.gov (United States)

Satheeshababu, B K; Shivakumar, K L

2013-03-01

The aim of this study was to synthesis the conjugated chitosan by covalent attachment of thiol moieties to the cationic polymer, mediated by a carbodiimide to improve permeation properties of chitosan. Thioglycolic acid was covalently attached to chitosan by the formation of amide bonds between the primary amino groups of the polymer and the carboxylic acid groups of thioglycolic acid. Hence, these polymers are called as thiomers or thiolated polymers. Conjugation of chitosan was confirmed by Fourier transform-infrared and differential scanning calorimetric analysis. Matrix type transdermal patches of carvedilol were prepared using the different proportions of chitosan and chitosan-thioglycolic acid conjugates (2:0, 1.7:0.3, 1.4:0.6, 1:1, 0.6:1.4 and 0.3:1.7) by solvent casting technique. Prepared matrix type patches were evaluated for their physicochemical characterization followed by in vitro evaluation. Selected formulations were subjected for their ex vivo studies on Wistar albino rat skin and human cadaver skin using the modified Franz diffusion cell. As the proportion of conjugated chitosan increased, the transdermal patches showed increased drug permeation. The mechanism of drug release was found to be nonFickian profiles. The present study concludes that the transdermal patches of carvedilol using conjugated chitosan with different proportions of chitosan were successfully developed to provide improved drug permeation. The transdermal patches can be a good approach to improve drug bioavailability by bypassing the extensive hepatic first-pass metabolism of the drug.

A Transdermal Measurement Platform Based on Microfluidics

Directory of Open Access Journals (Sweden)

Wen-Ying Huang

2017-01-01

Full Text Available The Franz diffusion cell is one of the most widely used devices to evaluate transdermal drug delivery. However, this static and nonflowing system has some limitations, such as a relatively large solution volume and skin area and the development of gas bubbles during sampling. To overcome these disadvantages, this study provides a proof of concept for miniaturizing models of transdermal delivery by using a microfluidic chip combined with a diffusion cell. The proposed diffusion microchip system requires only 80 μL of sample solution and provides flow circulation. Two model compounds, Coomassie Brilliant Blue G-250 and potassium ferricyanide, were successfully tested for transdermal delivery experiments. The diffusion rate is high for a high sample concentration or a large membrane pore size. The developed diffusion microchip system, which is feasible, can be applied for transdermal measurement in the future.

A Comprehensive Review on: Transdermal drug delivery systems.

OpenAIRE

Kharat, Rekha; Bathe, Ritesh Suresh

2016-01-01

Transdermal drug delivery system was introduced to overcome the difficulties of drug delivery through oral route. Despite their relatively higher costs, transdermal delivery systems have proved advantageous for delivery of selected drugs, such as estrogens, testosterone, clonidine and nitro-glycerine. Transdermal delivery provides a leading edge over injectable and oral routes by increasing patient compliance and avoiding first pass metabolism respectively. Topical  administration  of  therap...

Augmentation of Muscle Blood Flow by Ultrasound Cavitation Is Mediated by ATP and Purinergic Signaling.

Science.gov (United States)

Belcik, J Todd; Davidson, Brian P; Xie, Aris; Wu, Melinda D; Yadava, Mrinal; Qi, Yue; Liang, Sherry; Chon, Chae Ryung; Ammi, Azzdine Y; Field, Joshua; Harmann, Leanne; Chilian, William M; Linden, Joel; Lindner, Jonathan R

2017-03-28

Augmentation of tissue blood flow by therapeutic ultrasound is thought to rely on convective shear. Microbubble contrast agents that undergo ultrasound-mediated cavitation markedly amplify these effects. We hypothesized that purinergic signaling is responsible for shear-dependent increases in muscle perfusion during therapeutic cavitation. Unilateral exposure of the proximal hindlimb of mice (with or without ischemia produced by iliac ligation) to therapeutic ultrasound (1.3 MHz, mechanical index 1.3) was performed for 10 minutes after intravenous injection of 2×10 8 lipid microbubbles. Microvascular perfusion was evaluated by low-power contrast ultrasound perfusion imaging. In vivo muscle ATP release and in vitro ATP release from endothelial cells or erythrocytes were assessed by a luciferin-luciferase assay. Purinergic signaling pathways were assessed by studying interventions that (1) accelerated ATP degradation; (2) inhibited P2Y receptors, adenosine receptors, or K ATP channels; or (3) inhibited downstream signaling pathways involving endothelial nitric oxide synthase or prostanoid production (indomethacin). Augmentation in muscle perfusion by ultrasound cavitation was assessed in a proof-of-concept clinical trial in 12 subjects with stable sickle cell disease. Therapeutic ultrasound cavitation increased muscle perfusion by 7-fold in normal mice, reversed tissue ischemia for up to 24 hours in the murine model of peripheral artery disease, and doubled muscle perfusion in patients with sickle cell disease. Augmentation in flow extended well beyond the region of ultrasound exposure. Ultrasound cavitation produced an ≈40-fold focal and sustained increase in ATP, the source of which included both endothelial cells and erythrocytes. Inhibitory studies indicated that ATP was a critical mediator of flow augmentation that acts primarily through either P2Y receptors or adenosine produced by ectonucleotidase activity. Combined indomethacin and inhibition of

Chemical Penetration Enhancers for Transdermal Drug Delivery ...

African Journals Online (AJOL)

for transdermal administration. The permeation of drug through skin can be enhanced by both chemical penetration enhancement and physical methods. In this review, we have discussed the chemical penetration enhancement technology for transdermal drug delivery as well as the probable mechanisms of action.

Effect of modulated ultrasound parameters on ultrasound-induced thrombolysis

International Nuclear Information System (INIS)

Soltani, Azita; Volz, Kim R; Hansmann, Doulas R

2008-01-01

The potential of ultrasound to enhance enzyme-mediated thrombolysis by application of constant operating parameters (COP) has been widely demonstrated. In this study, the effect of ultrasound with modulated operating parameters (MOP) on enzyme-mediated thrombolysis was investigated. The MOP protocol was applied to an in vitro model of thrombolysis. The results were compared to a COP with the equivalent soft tissue thermal index (TIS) over the duration of ultrasound exposure of 30 min (p -2 ± 0.01 μm and 1.99 x 10 -2 ± 0.004 μm, respectively (p < 0.74). No signatures of inertial or stable cavitation were observed for either acoustic protocol. In conclusion, due to mechanisms other than cavitation, application of ultrasound with modulated operating parameters has the potential to significantly enhance the relative lysis enhancement compared to application of ultrasound with constant operating parameters.

A commentary on transdermal drug delivery systems in clinical trials.

Science.gov (United States)

Watkinson, Adam C

2013-09-01

The number of drugs available as marketed transdermal products is limited to those that exhibit the correct physicochemical and pharmacokinetic properties that enable their effective delivery across the skin. In this respect, there are less than 20 drugs that are currently marketed in the US and EU as products that deliver systemic levels of their active ingredients. An analysis of clinical trials conducted in the transdermal sector shows a similar picture with only nine drugs accounting for approximately 80% of all transdermal clinical trials listed on ClinicalTrials.gov. Those drugs for which there are very few transdermal trials listed consist mostly of molecules that are inherently unsuitable for transdermal delivery and serve as a clear warning to drug developers that the science that governs transdermal drug delivery is well reflected by the successes and failures of drugs in development as well as those that make it to the market. Copyright © 2013 Wiley Periodicals, Inc.

A multimodal instrument for real-time in situ study of ultrasound and cavitation mediated drug delivery

OpenAIRE

Bian, S; Seth, A; Daly, D; Carlisle, R; Stride, E

2017-01-01

The development of a multimodal instrument capable of real-time in situ measurements of cavitation activity and effect in tissue mimicking phantoms during ultrasound and cavitation mediated drug delivery experiments is described here. The instrument features an acoustic arm that can expose phantoms to high-intensity focused-ultrasound while measuring cavitation activity and an optical arm that monitors cavitation effect using confocal microscopy. This combination of modalities allows real-tim...

Estradiol Transdermal Patch

Science.gov (United States)

... menopause (change of life; the end of monthly menstrual periods). Transdermal estradiol is also used to prevent ... patch. Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Ultrasound mediated nanoparticle drug delivery

Science.gov (United States)

Mullin, Lee B.

Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems

Ultrasound Mediated Microbubbles Destruction Augmented Sonolysis: An In Vitro and In Vivo Study.

Science.gov (United States)

Cui, Hai; Zhu, Qiong; Gao, Yunhua; Xia, Hongmei; Tan, Kaibin; He, Ying; Liu, Zheng; Xu, Yali

2017-01-01

This study was aimed at exploring ultrasound mediated microbubbles destruction (UMMD) assisted sonolysis in both the in vitro and in vivo clots. Therapeutic ultrasound (TUS) and lipid microbubbles (MBs) were used in whole blood clots and divided into the control, TUS group, and TUS + MB group. Thrombolytic rates and microscopy were performed. Color Doppler flow imaging (CDFI) and angiography were performed to evaluate the recanalization rates and flow scores in femoral arterial thrombus (FAT) in rabbits. FAT were dyed with H&E. The average thrombolytic ratios of TUS + MB group were significantly higher than those of TUS group and the control group (both P cavitation via UMMD.

Ultrasound-mediated gene delivery of naked plasmid DNA in skeletal muscles: a case for bolus injections.

Science.gov (United States)

Sanches, Pedro Gomes; Mühlmeister, Mareike; Seip, Ralf; Kaijzel, Eric; Löwik, Clemens; Böhmer, Marcel; Tiemann, Klaus; Grüll, Holger

2014-12-10

Localized gene delivery has many potential clinical applications. However, the nucleic acids (e.g. pDNA and siRNA) are incapable of passively crossing the endothelium, cell membranes and other biological barriers which must be crossed to reach their intracellular targets. A possible solution is the use of ultrasound to burst circulating microbubbles inducing transient permeabilization of surrounding tissues which mediates nucleic acid extravasation and cellular uptake. In this study we report on an optimization of the ultrasound gene delivery technique. Naked pDNA (200 μg) encoding luciferase and SonoVue® microbubbles were co-injected intravenously in mice. The hindlimb skeletal muscles were exposed to ultrasound from a non-focused transducer (1 MHz, 1.25 MPa, PRI 30s) and injection protocols and total amounts as well as ultrasound parameters were systemically varied. Gene expression was quantified relative to a control using a bioluminescence camera system at day 7 after sonication. Bioluminescence ratios in sonicated/control muscles of up to 101× were obtained. In conclusion, we were able to specifically deliver genetic material to the selected skeletal muscles and overall, the use of bolus injections and high microbubble numbers resulted in increased gene expression reflected by stronger bioluminescence signals. Based on our data, bolus injections seem to be required in order to achieve transient highly concentrated levels of nucleic acids and microbubbles at the tissue of interest which upon ultrasound exposure should lead to increased levels of gene delivery. Thus, ultrasound mediated gene delivery is a promising technique for the clinical translation of localized drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

Multiscale modeling of transdermal drug delivery

Science.gov (United States)

Rim, Jee Eun

2006-04-01

This study addresses the modeling of transdermal diffusion of drugs, to better understand the permeation of molecules through the skin, and especially the stratum corneum, which forms the main permeation barrier of the skin. In transdermal delivery of systemic drugs, the drugs diffuse from a patch placed on the skin through the epidermis to the underlying blood vessels. The epidermis is the outermost layer of the skin and can be further divided into the stratum corneum (SC) and the viable epidermis layers. The SC consists of keratinous cells (corneocytes) embedded in the lipid multi-bilayers of the intercellular space. It is widely accepted that the barrier properties of the skin mostly arises from the ordered structure of the lipid bilayers. The diffusion path, at least for lipophilic molecules, seems to be mainly through the lipid bilayers. Despite the advantages of transdermal drug delivery compared to other drug delivery routes such as oral dosing and injections, the low percutaneous permeability of most compounds is a major difficulty in the wide application of transdermal drug delivery. In fact, many transdermal drug formulations include one or more permeation enhancers that increase the permeation of the drug significantly. During the last two decades, many researchers have studied percutaneous absorption of drugs both experimentally and theoretically. However, many are based on pharmacokinetic compartmental models, in which steady or pseudo-steady state conditions are assumed, with constant diffusivity and partitioning for single component systems. This study presents a framework for studying the multi-component diffusion of drugs coupled with enhancers through the skin by considering the microstructure of the stratum corneum (SC). A multiscale framework of modeling the transdermal diffusion of molecules is presented, by first calculating the microscopic diffusion coefficient in the lipid bilayers of the SC using molecular dynamics (MD). Then a

TRANSDERMAL DRUG DELIVERY AND METHODS TO ENHANCE IT

Directory of Open Access Journals (Sweden)

E. G. Kuznetsova

2016-01-01

Full Text Available The paper presents the common methods employed in recent years for enhancing transdermal delivery of drug substances when applying transdermal therapeutic delivery systems. The chemical, physical and mechanical methods to enhance the transport of macromolecular compounds through the skin are considered in details. 

3D printing applications for transdermal drug delivery.

Science.gov (United States)

Economidou, Sophia N; Lamprou, Dimitrios A; Douroumis, Dennis

2018-06-15

The role of two and three-dimensional printing as a fabrication technology for sophisticated transdermal drug delivery systems is explored in literature. 3D printing encompasses a family of distinct technologies that employ a virtual model to produce a physical object through numerically controlled apparatuses. The applicability of several printing technologies has been researched for the direct or indirect printing of microneedle arrays or for the modification of their surface through drug-containing coatings. The findings of the respective studies are presented. The range of printable materials that are currently used or potentially can be employed for 3D printing of transdermal drug delivery (TDD) systems is also reviewed. Moreover, the expected impact and challenges of the adoption of 3D printing as a manufacturing technique for transdermal drug delivery systems, are assessed. Finally, this paper outlines the current regulatory framework associated with 3D printed transdermal drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

[Comparative study on transdermal osmosis in vitro of Aconitum brachypodium liniment, gel and patcher].

Science.gov (United States)

Lin, Ya-ping; Zhao, Ying; Zhang, Yong-ping; Liang, Guang-yi

2007-02-01

To study the transdermal osmosis process of Aconitum brachypodum's liniment, gel and patcher to provide basis for selecting dosage form and controlling the quality. Taking the cumulate rate of transdermal as index, a imitated Fick's diffusion device was used for the investigating the transdermal osmosis course of the three preparations. The best transdermal mathematics models are obtained and the relations between the transdermal course and the release course are analysed. The three preparations have different characteristics of transdermal osmosis course. The liniment meets dynamics 0 order process, the gel and the patcher meet dynamic 0 order process of non-corroded drug system. And the relation is good cubic equation between their transdermal course and release course. The transdermal osmosis experiment in vitro for three preparations can provide basis for selecting dosage form and the quality control in future studies.

Dissolving Microneedle Arrays for Transdermal Delivery of Amphiphilic Vaccines.

Science.gov (United States)

An, Myunggi; Liu, Haipeng

2017-07-01

Amphiphilic vaccine based on lipid-polymer conjugates is a new type of vaccine capable of self-delivering to the immune system. When injected subcutaneously, amphiphilic vaccines efficiently target antigen presenting cells in the lymph nodes (LNs) via a unique albumin-mediated transport and uptake mechanism and induce potent humoral and cellular immune responses. However, whether this new type of vaccine can be administrated via a safe, convenient microneedle-based transdermal approach remains unstudied. For such skin barrier-disruption systems, a simple application of microneedle arrays (MNs) is desired to disrupt the stratum corneum, and for rapid and pain-free self-administration of vaccines into the skin, the anatomic place permeates with an intricate mesh of lymphatic vessels draining to LNs. Here the microneedle transdermal approach is combined with amphiphilic vaccines to create a simple delivery approach which efficiently traffic molecular vaccines into lymphatics and draining LNs. The rapid release of amphiphilic vaccines into epidermis upon application of dissolving MNs to the skin of mice generates potent cellular and humoral responses, comparable or superior to those elicited by traditional needle-based immunizations. The results suggest that the amphiphilic vaccines delivered by dissolving MNs can provide a simple and safer vaccination method with enhanced vaccine efficacy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ATR-FTIR and Raman spectroscopic investigation of the electroporation-mediated transdermal delivery of a nanocarrier system containing an antitumour drug.

Science.gov (United States)

Balázs, Boglárka; Sipos, Péter; Danciu, Corina; Avram, Stefana; Soica, Codruta; Dehelean, Cristina; Varju, Gábor; Erős, Gábor; Budai-Szűcs, Mária; Berkó, Szilvia; Csányi, Erzsébet

2016-01-01

The aim of the present work was the optimization of the transdermal delivery of a lyotropic liquid crystal genistein-based formulation (LLC-GEN). LLC was chosen as medium in view of the poor solubility of GEN in water. Membrane diffusion and penetration studies were carried out with a Franz diffusion cell, through a synthetic membrane in vitro, a chick chorioallantoic membrane ex ovo, and ex vivo excised human epidermis. Thereafter, LLC-GEN was combined with electroporation (EP) to enhance the transdermal drug delivery. The synergistic effect of EP was verified by in vivo ATR-FTIR and ex vivo Raman spectroscopy on hairless mouse skin.

Rotigotine transdermal patch for the treatment of Parkinson's Disease.

Science.gov (United States)

Perez-Lloret, Santiago; Rey, María Verónica; Ratti, Pietro Lucca; Rascol, Olivier

2013-02-01

Rotigotine, a non-ergot dopamine agonist, has been developed as a novel transdermal formulation. The rotigotine transdermal patch has received EMEA marketing authorization for the treatment of adult patients with early or advanced Parkinson's disease (PD) or with moderate to severe restless legs syndrome (RLS). FDA originally granted a marketing authorization for early PD, which was later suspended, and is now studying the authorization for RLS. The aim of this review is to review the pharmacokinetics, pharmacodynamics as well as the clinical efficacy and tolerability of the rotigotine transdermal patch in PD. Source material was identified using a PubMed search for the term 'rotigotine' and PD. Articles published up to January 2011 or abstract submitted to most relevant international neurology congresses were reviewed. The rotigotine transdermal patch is efficacious for the treatment of PD. Tolerability profile appears to be well within the range of that observed with other non-ergot dopamine agonists in PD. Application-site reactions were the most frequent adverse event, and they were considered mild to moderate in the majority of cases. The rotigotine transdermal patch offers a safe and efficacious alternative for the treatment of PD. Further studies should focus on the possibility that continuous dopamine stimulation by means of the transdermal patch has any influence on levodopa-related motor complications. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery

Directory of Open Access Journals (Sweden)

Vera ePaefgen

2015-09-01

Full Text Available Ultrasound is one of the most frequently used diagnostic methods. It is a non-invasive, comparably inexpensive imaging method with a broad spectrum of applications, which can be increased even more by using bubbles as contrast agents. There are various different types of bubbles: filled with different gases, composed of soft- or hard-shell materials, and ranging in size from nano- to micrometers. These intravascular contrast agents enable functional analyses, e.g. to acquire organ perfusion in real-time. Molecular analyses are achieved by coupling specific ligands to the bubbles’ shell, which bind to marker molecules in the area of interest. Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by ultrasound pulses to locally release the entrapped agent. Recent studies show that ultrasound contrast agents are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability. This review summarizes important steps in the development of ultrasound contrast agents and introduces the current clinical applications of contrast-enhanced ultrasound. Additionally, an overview of the recent developments in ultrasound probe design for functional and molecular diagnosis as well as for drug delivery is given.

Generation of ROS mediated by mechanical waves (ultrasound) and its possible applications.

Science.gov (United States)

Duco, Walter; Grosso, Viviana; Zaccari, Daniel; Soltermann, Arnaldo T

2016-10-15

The thermal decomposition of 9,10 diphenylanthracene peroxide (DPAO 2 ) generates DPA and a mix of triplet and singlet molecular oxygen. For DPAO 2 the efficiency to produce singlet molecular oxygen is 0.35. On the other hand, it has shown that many thermal reactions can be carried out through the interaction of molecules with ultrasound. Ultrasound irradiation can create hydrodynamic stress (sonomechanical process), inertial cavitation (pyrolitic process) and long range effects mediated by radicals or ROS. Sonochemical reactions can be originated by pyrolytic like process, shock mechanical waves, thermal reactions and radical and ROS mediated reactions. Sonolysis of pure water can yield hydrogen or hydroxyl radicals and hydrogen peroxide (ROS). When DPAO 2 in 1,4 dioxane solution is treated with 20 or 24kHz and different power intensity the production of molecular singlet oxygen is observed. Specific scavengers like tetracyclone (TC) are used to demonstrate it. The efficiency now is 0.85 showing that the sonochemical process is much more efficient that the thermal one. Another endoperoxide, artemisinin was also studied. Unlike the concept of photosensitizer of photodynamic therapy, in spite of large amount of reported results in literature, the term sonosensitizer and the sonosensitization process are not well defined. We define sonosensitized reaction as one in which a chemical species decompose as consequence of cavitation phenomena producing ROS or other radicals and some other target species does undergo a chemical reaction. The concept could be reach rapidly other peroxides which are now under experimental studies. For artemisinin, an important antimalarian and anticancer drug, was established that ultrasound irradiation increases the effectiveness of the treatment but without any explanation. We show that artemisinin is an endoperoxide and behaves as a sonosensitizer in the sense of our definition. Copyright © 2016 Elsevier Inc. All rights reserved.

Future of the transdermal drug delivery market--have we barely touched the surface?

Science.gov (United States)

Watkinson, Adam C; Kearney, Mary-Carmel; Quinn, Helen L; Courtenay, Aaron J; Donnelly, Ryan F

2016-01-01

Transdermal drug delivery is the movement of drugs across the skin for absorption into the systemic circulation. Transfer of the drug can occur via passive or active means; passive transdermal products do not disrupt the stratum corneum to facilitate delivery whereas active technologies do. Due to the very specific physicochemical properties necessary for successful passive transdermal drug delivery, this sector of the pharmaceutical industry is relatively small. There are many well-documented benefits of this delivery route however, and as a result there is great interest in increasing the number of therapeutic substances that can be delivered transdermally. This review discusses the various transdermal products that are currently/have been marketed, and the paths that led to their success, or lack of. Both passive and active transdermal technologies are considered with the advantages and limitations of each highlighted. In addition to marketed products, technologies that are in the investigative stages by various pharmaceutical companies are reviewed. Passive transdermal drug delivery has made limited progress in recent years, however with the ongoing intense research into active technologies, there is great potential for growth within the transdermal delivery market. A number of active technologies have already been translated into marketed products, with other platforms including microneedles, rapidly progressing towards commercialisation.

Pharmacokinetic characteristics of formulated alendronate transdermal delivery systems in rats and humans.

Science.gov (United States)

Choi, Ahyoung; Gang, Hyesil; Whang, Jiae; Gwak, Hyesun

2010-05-01

The objective of this study was to examine the absorption of alendronate from formulated transdermal delivery systems in rats and humans. When alendronate was applied to rats by transdermal delivery systems (7.2 mg) and oral administration (30 mg/kg), a statistically significant difference was found in the amount remaining to be excreted at time t (Ae(t)) and the amount remaining to be excreted at time 0 (Ae(infinity)) (p transdermal delivery systems. There was a linear relationship (r(2) = 0.9854) between the drug loading dose and Ae(infinity). The Ae(infinity) values from the transdermal delivery system containing 6% caprylic acid (53.8 mg as alendronate) and an oral product (Fosamax), 70 mg as alendronate) in humans were 127.0 +/- 34.2 microg and 237.2 +/- 56.3 microg, respectively. The dose-adjusted relative Ae(infinity) ratio of the transdermal delivery system to oral product was calculated to be 69.7%. The long half-life of alendronate in the transdermal delivery system (50.6 +/- 6.4 h), compared to that of the oral product (3.5 +/- 1.1 h) could allow less-frequent dosing. In conclusion, this study showed that a transdermal delivery system containing 6% caprylic acid in PG could be a favorable alternative for alendronate administration.

Effect of albumin and dextrose concentration on ultrasound and microbubble mediated gene transfection in vivo.

Science.gov (United States)

Browning, Richard J; Mulvana, Helen; Tang, Meng-Xing; Hajnal, Jo V; Wells, Dominic J; Eckersley, Robert J

2012-06-01

Ultrasound and microbubble mediated gene transfection has great potential for site-selective, safe gene delivery. Albumin-based microbubbles have shown the greatest transfection efficiency but have not been optimised specifically for this purpose. Additionally, few studies have highlighted desirable properties for transfection specific microbubbles. In this article, microbubbles were made with 2% or 5% (w/v) albumin and 20% or 40% (w/v) dextrose solutions, yielding four distinct bubble types. These were acoustically characterised and their efficiency in transfecting a luciferase plasmid (pGL4.13) into female, CD1 mice myocardia was measured. For either albumin concentration, increasing the dextrose concentration increased scattering, attenuation and resistance to ultrasound, resulting in significantly increased transfection. A significant interaction was noted between albumin and dextrose; 2% albumin bubbles made with 20% dextrose showed the least transfection but the most transfection with 40% dextrose. This trend was seen for both nonlinear scattering and attenuation behaviour but not for resistance to ultrasound or total scatter. We have determined that the attenuation behaviour is an important microbubble characteristic for effective gene transfection using ultrasound. Microbubble behaviour can also be simply controlled by altering the initial ingredients used during manufacture. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

The impact of vaporized nanoemulsions on ultrasound-mediated ablation.

Science.gov (United States)

Zhang, Peng; Kopechek, Jonathan A; Porter, Tyrone M

2013-01-01

The clinical feasibility of using high-intensity focused ultrasound (HIFU) for ablation of solid tumors is limited by the high acoustic pressures and long treatment times required. The presence of microbubbles during sonication can increase the absorption of acoustic energy and accelerate heating. However, formation of microbubbles within the tumor tissue remains a challenge. Phase-shift nanoemulsions (PSNE) have been developed as a means for producing microbubbles within tumors. PSNE are emulsions of submicron-sized, lipid-coated, and liquid perfluorocarbon droplets that can be vaporized into microbubbles using short (5 MPa) acoustic pulses. In this study, the impact of vaporized phase-shift nanoemulsions on the time and acoustic power required for HIFU-mediated thermal lesion formation was investigated in vitro. PSNE containing dodecafluoropentane were produced with narrow size distributions and mean diameters below 200 nm using a combination of sonication and extrusion. PSNE was dispersed in albumin-containing polyacrylamide gel phantoms for experimental tests. Albumin denatures and becomes opaque at temperatures above 58°C, enabling visual detection of lesions formed from denatured albumin. PSNE were vaporized using a 30-cycle, 3.2-MHz, at an acoustic power of 6.4 W (free-field intensity of 4,586 W/cm(2)) pulse from a single-element, focused high-power transducer. The vaporization pulse was immediately followed by a 15-s continuous wave, 3.2-MHz signal to induce ultrasound-mediated heating. Control experiments were conducted using an identical procedure without the vaporization pulse. Lesion formation was detected by acquiring video frames during sonication and post-processing the images for analysis. Broadband emissions from inertial cavitation (IC) were passively detected with a focused, 2-MHz transducer. Temperature measurements were acquired using a needle thermocouple. Bubbles formed at the HIFU focus via PSNE vaporization enhanced HIFU-mediated heating

Stabilizing in vitro ultrasound-mediated gene transfection by regulating cavitation.

Science.gov (United States)

Lo, Chia-Wen; Desjouy, Cyril; Chen, Shing-Ru; Lee, Jyun-Lin; Inserra, Claude; Béra, Jean-Christophe; Chen, Wen-Shiang

2014-03-01

It is well known that acoustic cavitation can facilitate the inward transport of genetic materials across cell membranes (sonoporation). However, partially due to the unstationary behavior of the initiation and leveling of cavitation, the sonoporation effect is usually unstable, especially in low intensity conditions. A system which is able to regulate the cavitation level during sonication by modulating the applied acoustic intensity with a feedback loop is implemented and its effect on in vitro gene transfection is tested. The regulated system provided better time stability and reproducibility of the cavitation levels than the unregulated conditions. Cultured hepatoma cells (BNL) mixed with 10 μg luciferase plasmids are exposed to 1-MHz pulsed ultrasound with or without cavitation regulation, and the gene transfection efficiency and cell viability are subsequently assessed. Experimental results show that for all exposure intensities (low, medium, and high), stable and intensity dependent, although not higher, gene expression could be achieved in the regulated cavitation system than the unregulated conditions. The cavitation regulation system provides a better control of cavitation and its bioeffect which are crucial important for clinical applications of ultrasound-mediated gene transfection. Copyright © 2013 Elsevier B.V. All rights reserved.

Transdermal drug delivery: feasibility for treatment of superficial bone stress fractures.

Science.gov (United States)

Aghazadeh-Habashi, Ali; Yang, Yang; Tang, Kathy; Lőbenberg, Raimar; Doschak, Michael R

2015-12-01

Transdermal drug delivery offers the promise of effective drug therapy at selective sites of pathology whilst reducing systemic exposure to the pharmaceutical agents in off-target organs and tissues. However, that strategy is often limited to cells comprising superficial tissues of the body (rarely to deeper bony structures) and mostly indicated with small hydrophobic pharmacological agents, such as steroid hormones and anti-inflammatory gels to skin, muscle, and joints. Nonetheless, advances in transdermal liposomal formulation have rendered the ability to readily incorporate pharmacologically active hydrophilic drug molecules and small peptide biologics into transdermal dosage forms to impart the effective delivery of those bioactive agents across the skin barrier to underlying superficial tissue structures including bone, often enhanced by some form of electrical, chemical, and mechanical facilitation. In the following review, we evaluate transdermal drug delivery systems, with a particular focus on delivering therapeutic agents to treat superficial bone pain, notably stress fractures. We further introduce and discuss several small peptide hormones active in bone (such as calcitonins and parathyroid hormone) that have shown potential for transdermal delivery, often under the added augmentation of transdermal drug delivery systems that employ lipo/hydrophilicity, electric charge, and/or microprojection facilitation across the skin barrier.

Recent trends in challenges and opportunities of Transdermal drug delivery system

OpenAIRE

P.M.Patil; P.D.Chaudhari; Jalpa K.Patel; K.A.Kedar; P.P.Katolkar

2012-01-01

Drug delivery system relates to the production of a drug, its delivery medium, and the way of administration. Drug delivery systems are even used for administering nitroglycerin. Transdermal drug delivery system is the system in which the delivery of the active ingredients of the drug occurs by the means of skin. Various types of transdermal patches are used. There are various methods to enhance the transdermal drug delivery system. But using microfabricated microneedles drugs are delivered v...

Current advances in the fabrication of microneedles for transdermal delivery

NARCIS (Netherlands)

Indermun, S.; Luttge, R.; Choonara, Y.E.; Kumar, Pradeep; Toit, Du L.C.; Modi, G.; Pillay, V.

2014-01-01

The transdermal route is an excellent site for drug delivery due to the avoidance of gastric degradation and hepatic metabolism, in addition to easy accessibility. Although offering numerous attractive advantages, many available transdermal systems are not able to deliver drugs and other compounds

Transdermal fentanyl matrix patches Matrifen and Durogesic DTrans are bioequivalent

DEFF Research Database (Denmark)

Kress, Hans G; Boss, Hildegard; Delvin, Thomas

2010-01-01

AIM: The pharmacokinetic profiles of the two commercially available transdermal fentanyl patches Matrifen (100 microg/h) and Durogesic DTrans (100 microg/h), used to manage severe chronic pain, were compared regarding their systemic exposure, rate of absorption, and safety. METHODS: Transdermal m...

How can lipid nanocarriers improve transdermal delivery of olanzapine?

Science.gov (United States)

Iqbal, Nimra; Vitorino, Carla; Taylor, Kevin M G

2017-06-01

The development of a transdermal nanocarrier drug delivery system with potential for the treatment of psychiatric disorders, such as schizophrenia and bipolar disorder, is described. Lipid nanocarriers (LN), encompassing various solid:liquid lipid compositions were formulated and assessed as potential nanosystems for transdermal delivery of olanzapine. A previously optimized method of hot high pressure homogenization (HPH) was adopted for the production of the LN, which comprised solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Precirol  ® was selected as the solid lipid for progression of studies. SLN exhibited the best performance for transdermal delivery of olanzapine, based on in vitro release and permeation studies, coupled with results from physicochemical characterization of several solid:liquid lipid formulations. Stability tests, performed to give an indication of long-term storage behavior of the formulations, were in good agreement with previous studies for the best choice of solid:liquid lipid ratio. Overall, these findings highlight the SLN-based formulation as promising for the further inclusion in and production of transdermal patches, representing an innovative therapeutic approach.

Transdermal and Topical Drug Administration in the Treatment of Pain

Directory of Open Access Journals (Sweden)

Wojciech Leppert

2018-03-01

Full Text Available The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients’ age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non–steroidal anti–inflammatory drugs (NSAIDs applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti–inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.

[Matrix transdermal systems for caffeine delivery based on polymer and emulsion compounds].

Science.gov (United States)

Kuznetsova, E G; Kuryleva, O M; Salomatina, L A; Sevast'ianov, V I

2008-01-01

The goal of this work was to develop and test transdermal therapeutic systems for caffeine delivery. In vitro experiments showed that the rate of caffeine diffusion through untreated rabbit skin from a transdermal therapeutic systems based on polymer compound containing 50 mg medicine was 67.2 (9.1 microg/cm2h; for a system based on emulsion compound it was 173 (19 microg/cm2h. Methods for studying the caffeine release rate and quantitative measurement of caffeine content in the emulsion-based transdermal therapeutic system were developed. These methods are required to obtain data for standard drug documentation. The results of in vivo experiments in rabbits showed the absence of irritating effect of the emulsion-based transdermal therapeutic system. The obtained data on the specific efficiency of the transdermal therapeutic systems for caffeine delivery (50 mg) in healthy volunteers showed that this medicine could be used as a nonnarcotic psychoactivator for improving mental and physical activities and attention concentration.

Intravascular forward-looking ultrasound transducers for microbubble-mediated sonothrombolysis.

Science.gov (United States)

Kim, Jinwook; Lindsey, Brooks D; Chang, Wei-Yi; Dai, Xuming; Stavas, Joseph M; Dayton, Paul A; Jiang, Xiaoning

2017-06-14

Effective removal or dissolution of large blood clots remains a challenge in clinical treatment of acute thrombo-occlusive diseases. Here we report the development of an intravascular microbubble-mediated sonothrombolysis device for improving thrombolytic rate and thus minimizing the required dose of thrombolytic drugs. We hypothesize that a sub-megahertz, forward-looking ultrasound transducer with an integrated microbubble injection tube is more advantageous for efficient thrombolysis by enhancing cavitation-induced microstreaming than the conventional high-frequency, side-looking, catheter-mounted transducers. We developed custom miniaturized transducers and demonstrated that these transducers are able to generate sufficient pressure to induce cavitation of lipid-shelled microbubble contrast agents. Our technology demonstrates a thrombolysis rate of 0.7 ± 0.15 percent mass loss/min in vitro without any use of thrombolytic drugs.

Engineering approaches to transdermal drug delivery: a tribute to contributions of prof. Robert Langer.

Science.gov (United States)

Mitragotri, S

2013-01-01

Transdermal drug delivery continues to provide an advantageous route of drug administration over injections. While the number of drugs delivered by passive transdermal patches has increased over the years, no macromolecule is currently delivered by the transdermal route. Substantial research efforts have been dedicated by a large number of researchers representing varied disciplines including biology, chemistry, pharmaceutics and engineering to understand, model and overcome the skin's barrier properties. This article focuses on engineering contributions to the field of transdermal drug delivery. The article pays tribute to Prof. Robert Langer, who pioneered the engineering approach towards transdermal drug delivery. Over a period spanning nearly 25 years since his first publication in the field of transdermal drug delivery, Bob Langer has deeply impacted the field by quantitative analysis and innovative engineering. At the same time, he has inspired several generations of engineers by collaborations and mentorship. His scientific insights, innovative technologies, translational efforts and dedicated mentorship have transformed the field. © 2013 S. Karger AG, Basel.

Systemic delivery of β-blockers via transdermal route for hypertension

Science.gov (United States)

Ahad, Abdul; Al-Jenoobi, Fahad I.; Al-Mohizea, Abdullah M.; Akhtar, Naseem; Raish, Mohammad; Aqil, Mohd.

2014-01-01

Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later. PMID:26702253

Transdermal microneedles for drug delivery applications

International Nuclear Information System (INIS)

Teo, Ai Ling; Shearwood, Christopher; Ng, Kian Chye; Lu Jia; Moochhala, Shabbir

2006-01-01

Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to painlessly penetrate the sc barrier has previously been proposed. In this paper, we will review the different microneedles that are currently being developed as well as our own efforts in this area. Based on our experiences, we will offer our view on the key parameters for effective transdermal microneedle design as well as future directions in this area

Transdermal microneedles for drug delivery applications

Energy Technology Data Exchange (ETDEWEB)

Teo, Ai Ling [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Shearwood, Christopher [School of Mechanical and Aerospace Engineering, 50 Nanyang Avenue, Singapore 639798 (Singapore); Ng, Kian Chye [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Lu Jia [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore)]. E-mail: mshabbir@dso.org.sg

2006-07-25

Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to painlessly penetrate the sc barrier has previously been proposed. In this paper, we will review the different microneedles that are currently being developed as well as our own efforts in this area. Based on our experiences, we will offer our view on the key parameters for effective transdermal microneedle design as well as future directions in this area.

Acoustically accessible window determination for ultrasound mediated treatment of glycogen storage disease type Ia patients

Science.gov (United States)

Wang, Shutao; Raju, Balasundar I.; Leyvi, Evgeniy; Weinstein, David A.; Seip, Ralf

2012-10-01

Glycogen storage disease type Ia (GSDIa) is caused by an inherited single-gene defect resulting in an impaired glycogen to glucose conversion pathway. Targeted ultrasound mediated delivery (USMD) of plasmid DNA (pDNA) to liver in conjunction with microbubbles may provide a potential treatment for GSDIa patients. As the success of USMD treatments is largely dependent on the accessibility of the targeted tissue by the focused ultrasound beam, this study presents a quantitative approach to determine the acoustically accessible liver volume in GSDIa patients. Models of focused ultrasound beam profiles for transducers of varying aperture and focal lengths were applied to abdomen models reconstructed from suitable CT and MRI images. Transducer manipulations (simulating USMD treatment procedures) were implemented via transducer translations and rotations with the intent of targeting and exposing the entire liver to ultrasound. Results indicate that acoustically accessible liver volumes can be as large as 50% of the entire liver volume for GSDIa patients and on average 3 times larger compared to a healthy adult group due to GSDIa patients' increased liver size. Detailed descriptions of the evaluation algorithm, transducer-and abdomen models are presented, together with implications for USMD treatments of GSDIa patients and transducer designs for USMD applications.

Potential and problems in ultrasound-responsive drug delivery systems

Directory of Open Access Journals (Sweden)

Zhao YZ

2013-04-01

Full Text Available Ying-Zheng Zhao,1,3 Li-Na Du,2 Cui-Tao Lu,1 Yi-Guang Jin,2 Shu-Ping Ge3 1Wenzhou Medical College, Wenzhou City, Zhejiang Province, 2Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 3St Christopher’s Hospital for Children/Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. Keywords: ultrasound, targeted therapy, clinical application

Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example.

Science.gov (United States)

Chew, Marci L; Mordenti, Joyce; Yeoh, Thean; Ranade, Gautam; Qiu, Ruolun; Fang, Juanzhi; Liang, Yali; Corrigan, Brian

2016-08-01

Transdermal delivery has the potential to offer improved bioavailability by circumventing first-pass gut and hepatic metabolism. This study evaluated the pharmacokinetics of oral immediate release and transdermal latrepirdine in extensive and poor CYP2D6 metabolizers (EM/PM). Latrepirdine transdermal solution was prepared extemporaneously. The solution was applied with occlusive dressing to upper or middle back for 24 h. Each subject received a single dose of 8.14 mg oral, 5 mg transdermal, and 10 mg transdermal (EMs only) latrepirdine free base in a fixed sequence. Twelve EMs and 7 PMs (50-79 years) enrolled and completed the study. Latrepirdine was well tolerated following both routes of administration. Dose-normalized latrepirdine total exposures were approximately 11-fold and 1.5-fold higher in EMs and PMs, respectively following administration of transdermal relative to oral. Differences between EM and PM latrepirdine exposures were decreased, with PMs having 1.9- and 2.7-fold higher peak and total exposures, respectively, following transdermal administration compared to 11- and 20-fold higher exposures, respectively, following oral administration. Transdermal delivery can potentially mitigate the large intersubject differences observed with compounds metabolized primarily by CYP2D6. Transdermal delivery was readily accomplished in the clinic using an extemporaneously prepared solution [NCT00990613].

Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery.

Science.gov (United States)

Szunerits, Sabine; Boukherroub, Rabah

2018-01-01

Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum , the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section "Frontiers in Bioengineering and Biotechnology," the advances in this field and the handful of

Pharmacokinetics of 2 Formulations of Transdermal Fentanyl in Cynomolgus Macaques (Macaca fascicularis)

Science.gov (United States)

Carlson, Amy M; Kelly, Richard; Fetterer, David P; Rico, Pedro J; Bailey, Emily J

2016-01-01

Fentanyl is a μ-opioid agonist that often is used as the analgesic component for balanced anesthesia in both human and veterinary patients. Minimal information has been published regarding appropriate dosing, and the pharmacokinetics of fentanyl are unknown in NHP. The pharmacokinetic properties of 2 transdermal fentanyl delivery methods, a solution (2.6 and 1.95 mg/kg) and a patch (25 µg/h), were determined when applied topically to the dorsal scapular area of cynomolgus macaques (Macaca fascicularis). Serum fentanyl concentrations were analyzed by using liquid chromatography–mass spectrometry. Compared with the patch, the transdermal fentanyl solution generated higher drug concentrations over longer time. Adverse reactions occurred in the macaques that received the transdermal fentanyl solution at 2.6 mg/kg. Both preparations showed significant interanimal variability in the maximal serum drug levels, time to achieve maximal fentanyl levels, elimination half-life, and AUC values. Both the maximal concentration and the time at which this concentration occurred were increased in macaques compared with most other species after application of the transdermal fentanyl patch and compared with dogs after application of the transdermal fentanyl solution. The pharmacokinetic properties of transdermal fentanyl in macaques are markedly different from those in other veterinary species and preclude its use as a long-acting analgesic drug in NHP. PMID:27423151

Population pharmacokinetic model of transdermal nicotine delivered from a matrix-type patch.

Science.gov (United States)

Linakis, Matthew W; Rower, Joseph E; Roberts, Jessica K; Miller, Eleanor I; Wilkins, Diana G; Sherwin, Catherine M T

2017-12-01

Nicotine addiction is an issue faced by millions of individuals worldwide. As a result, nicotine replacement therapies, such as transdermal nicotine patches, have become widely distributed and used. While the pharmacokinetics of transdermal nicotine have been extensively described using noncompartmental methods, there are few data available describing the between-subject variability in transdermal nicotine pharmacokinetics. The aim of this investigation was to use population pharmacokinetic techniques to describe this variability, particularly as it pertains to the absorption of nicotine from the transdermal patch. A population pharmacokinetic parent-metabolite model was developed using plasma concentrations from 25 participants treated with transdermal nicotine. Covariates tested in this model included: body weight, body mass index, body surface area (calculated using the Mosteller equation) and sex. Nicotine pharmacokinetics were best described with a one-compartment model with absorption based on a Weibull distribution and first-order elimination and a single compartment for the major metabolite, cotinine. Body weight was a significant covariate on apparent volume of distribution of nicotine (exponential scaling factor 1.42). After the inclusion of body weight in the model, no other covariates were significant. This is the first population pharmacokinetic model to describe the absorption and disposition of transdermal nicotine and its metabolism to cotinine and the pharmacokinetic variability between individuals who were administered the patch. © 2017 The British Pharmacological Society.

Transdermal nitroglycerine enhances postoperative analgesia of intrathecal neostigmine following abdominal hysterectomies

Directory of Open Access Journals (Sweden)

Fareed Ahmed

2010-01-01

Full Text Available This study was carried out to assess the effect of nitroglycerine (transdermal on intrathecal neostigmine with bupivacaine on postoperative analgesia and note the incidence of adverse effects, if any. After taking informed consent, 120 patients of ASA Grade I and II were systematically randomised into four groups of 30 each. Patients were premedicated with midazolam 0.05 mg/kg intravenously and hydration with Ringer′s lactate solution 10ml/kg preoperatively in the holding room. Group I patients received Intrathecal injection of 15 mg bupivacaine with 1ml of normal saline and transdermal placebo patch. Group II patients received Intrathecal injection of 15 mg bupivacaine with 5 mcg of neostigmine and transdermal placebo patch. Group III patients received Intrathecal injection of 15 mg bupivacaine with 1ml of normal saline with transdermal nitroglycerine patch (5 mg/24 hours. Group IV patients received Intrathecal injection of 15 mg bupivacaine with 5mcg of neostigmine and transdermal nitroglycerine patch (5 mg/24 hours, applied on a non anaesthetised area after 20 minutes. Groups were demographically similar and did not differ in intraoperative characteristics like sensory block, motor block, haemodynamic parameters and SpO 2 . The mean duration of analgesia was 202.17 minutes, 407.20 minutes, 207.53 minutes and 581.63 minutes in control group (I, neostigmine group (II, nitroglycerine group (III and nitroglycerine neostigmine group (IV respectively (P< 0.01. To conclude, our results show that transdermal nitroglycerine itself does not show any analgesic potential but it enhances the analgesic potential of intrathecal neostigmine.

Treatment with subcutaneous and transdermal fentanyl: results from a population pharmacokinetic study in cancer patients.

Science.gov (United States)

Oosten, Astrid W; Abrantes, João A; Jönsson, Siv; de Bruijn, Peter; Kuip, Evelien J M; Falcão, Amílcar; van der Rijt, Carin C D; Mathijssen, Ron H J

2016-04-01

Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route. Fifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model. A one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h(-1), respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed. We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route.

Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway: an overview.

Science.gov (United States)

Naves, Lucas; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Soares, Graça

2017-05-01

In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and Drug Administration approved synthetic polymers in designing versatile drug delivery carriers for different drug administration routes, including transdermal drug delivery. The present review provides a brief introduction over the transdermal drug delivery and PLGA as a material in context to its role in designing drug delivery vehicles. Attempts are made to compile literatures over PLGA-based drug delivery vehicles, including microneedles, nanoparticles, and nanofibers and their role in transdermal drug delivery of different therapeutic agents. Different nanostructure evaluation techniques with their working principles are briefly explained.

Effect of components (polymer, plasticizer and solvent as a variable in fabrication of diclofenac transdermal patch

Directory of Open Access Journals (Sweden)

Chetna Modi

2012-01-01

Full Text Available Transdermal drug delivery influence consumer acceptance and marked increase in bioavailability of some drugs which undergoes hepatic first-pass metabolism. Fabrication of transdermal patch requires lots of attention regarding the amount of components used for it. Because of varied nature of polymer and plasticizer, transdermal patches have different properties and different drug release. This study is on the basis to evaluate the amount to be needed for fabrication of diclofenac transdermal patch. Study shows that Hydroxy Propyl Methyl Cellulose has great influence on transdermal patch, if it is used alone in combination with glycerin or PEG-4000 plasticizer.

Assessment of simvastatin niosomes for pediatric transdermal drug delivery.

Science.gov (United States)

Zidan, Ahmed S; Hosny, Khaled M; Ahmed, Osama A A; Fahmy, Usama A

2016-06-01

The prevalence of childhood dyslipidemia increases and is considered as an important risk factor for the incidence of cardiovascular disease in the adulthood. To improve dosing accuracy and facilitate the determination of dosing regimens in function of the body weight, the proposed study aims at preparing transdermal niosomal gels of simvastatin as possible transdermal drug delivery system for pediatric applications. Twelve formulations were prepared to screen the influence of formulation and processing variables on critical niosomal characteristics. Nano-sized niosomes with 0.31 μm number-weighted size displayed highest simvastatin release rate with 8.5% entrapment capacity. The niosomal surface coverage by negative charges was calculated according to Langmuir isotherm with n = 0.42 to suggest that the surface association was site-independent, probably producing surface rearrangements. Hypolipidemic activities after transdermal administration of niosomal gels to rats showed significant reduction in cholesterol and triglyceride levels while increasing plasma high-density lipoproteins concentration. Bioavailability estimation in rats revealed an augmentation in simvastatin bioavailability by 3.35 and 2.9 folds from formulation F3 and F10, respectively, compared with oral drug suspension. Hence, this transdermal simvastatin niosomes not only exhibited remarkable potential to enhance its bioavailability and hypolipidemic activity but also considered a promising pediatric antihyperlipidemic formulation.

Efficient Transdermal Delivery of Benfotiamine in an Animal Model

OpenAIRE

Varadi, Gyula; Zhu, Zhen; G. Carter, Stephen

2015-01-01

We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake.  Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-...

Development, characterization & invivo evaluation of proniosomal based transdermal delivery system of Atenolol

Directory of Open Access Journals (Sweden)

S. Ramkanth

2018-06-01

Full Text Available The potential of proniosomes as a transdermal drug delivery system for Atenolol was investigated by encapsulating the drug in various formulations of proniosomal gel composed of various ratios of sorbitan fatty acid esters, cholesterol, lecithin prepared by Coacervation-phase separation method. The objectives of the present study were to define effects on the antihypertension activity and pharmacokinetics of a novel transdermal Proniosomal gel incorporating Atenolol. The formulated systems were characterized in vitro for size, drug entrapment, In vitro and in vivo drug permeation profiles and vesicular stability at different storage conditions. The optimized Atenolol proniosomes (AT8 showed nanometric vesicle size, high entrapment efficiency and marked enhancement in transdermal permeation. The prepared Proniosomal gel showed the relative bioavailability of 365.38 fold increased for AT8 than oral. The maximal concentrations (Cmax, of drug were significantly reduced while the areas under the plasma concentration–time curve (AUC, and mean residence times (MRT, t1/2 were evidently increased and extended, respectively. The results suggest that proniosomes can act as promising carrier which offers an alternative approach for transdermal delivery of Atenolol. Keywords: Proniosomes, Atenolol, Niosomes, Pharmacokinetic study, Transdermal delivery

Transdermal carbamate poisoning – a case of misuse

Directory of Open Access Journals (Sweden)

Lalit Kumar Rajbanshi

2017-01-01

Full Text Available Acute pesticide poisoning is a common mode of intentional self harm. Oral ingestion is the usual mode of poisoning. However, inhalation, accidental or occupational transdermal exposure leading to acute or chronic poisoning can be the other route of poisoning. It has been seen that the purpose of poising is suicidal intensity in most of the cases. We report an unusual case where the victim had acute pesticide poisoning through transdermal route that was intended for non suicidal purpose. The patient was managed successfully with immediate decontamination and adequate antidote.

Ultrasound-mediated method for rapid delivery of nano-particles into cells for intracellular surface-enhanced Raman spectroscopy and cancer cell screening

International Nuclear Information System (INIS)

Feng, Shangyuan; Li, Zhihua; Chen, Guannan; Huang, Shaohua; Huang, Zufang; Li, Yongzeng; Lin, Juqiang; Chen, Rong; Lin, Duo; Zeng, Haishan

2015-01-01

Surface-enhanced Raman spectroscopy (SERS) is a powerful technology for providing finger-printing information of cells. A big challenge has been the long time duration and inefficient uptake of metal nano-particles into living cells as substrate for SERS analysis. Herein, a simple method (based on ultrasound) for the rapid transfer of silver nanoparticles (NPs) into living cells for intracellular SERS spectroscopy was presented. In this study, the ultrasound-mediated method for NP delivery overcame the shortcoming of ‘passive uptake’, and achieved quick acquisition of reproducible SERS spectra from living human nasopharyngeal carcinoma cell lines (C666 and CNE1) and normal nasopharyngeal cell line (NP69). Tentative assignment of the Raman bands in the measured SERS spectra showed cancer cell specific biomolecular differences, including significantly lower DNA concentrations and higher protein concentrations in cancerous nasopharyngeal cells as compared to those of normal cells. Combined with PCA–LDA multivariate analysis, ultrasound-mediated cell SERS spectroscopy differentiated the cancerous cells from the normal nasopharyngeal cells with high diagnostic accuracy (98.7%), demonstrating great potential for high-throughput cancer cell screening applications. (paper)

Transdermal Delivery of Drugs with Microneedles—Potential and Challenges

Directory of Open Access Journals (Sweden)

Kevin Ita

2015-06-01

Full Text Available Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use.

Microneedle-based drug delivery systems for transdermal route.

Science.gov (United States)

Pierre, Maria Bernadete Riemma; Rossetti, Fabia Cristina

2014-03-01

Transdermal delivery offers an attractive, noninvasive administration route but it is limited by the skin's barrier to penetration. Minimally invasive techniques, such as the use of microneedles (MNs), bypass the stratum corneum (SC) barrier to permit the drug's direct access to the viable epidermis. These novel micro devices have been developed to puncture the skin for the transdermal delivery of hydrophilic drugs and macromolecules, including peptides, DNA and other molecules, that would otherwise have difficulty passing the outermost layer of the skin, the SC. Using the tools of the microelectronics industry, MNs have been fabricated with a range of sizes, shapes and materials. MNs have been shown to be robust enough to penetrate the skin and dramatically increase the skin permeability of several drugs. Moreover, MNs have reduced needle insertion pain and tissue trauma and provided controlled delivery across the skin. This review focuses on the current state of the art in the transdermal delivery of drugs using various types of MNs and developments in the field of microscale devices, as well as examples of their uses and clinical safety.

Development and evaluation of transdermal organogels containing nicorandil.

Science.gov (United States)

Madan, J R; Sagar, Banode; Chellappan, Dinesh K; Dua, Kamal

2013-01-01

The objective of the study was to formulate a transdermal product containing Nicorandil as a model drug, because it has been first drug of choice to treat angina and hypertension. A further objective was to reduce its side effects. The transdermal product was prepared using various synthetic and natural gelling agents such as Carbopol 934p, Carbopol 974p, HPMC K15M and HPMC K100M. Various penetration enhancers were incorporated to enhance the diffusion across the rat skin. A further objective was to formulate organogels and minimize the concentration of penetration enhancer to 50% of the concentration used in gels and yet to achieve the maximum drug release. The prepared formulations were evaluated for their physical appearance, viscosity, spreadability, drug content and freeze thaw cycle. Based on in vitro studies across rat skin and human cadaver skin it was concluded that Nicrorandil transdermal organogel formulation using HPMC K100M with 2% w/w Transcutol-P shows increase in cumulative diffusion of Nicorandil amongst all other formulations.

Transdermal Spray in Hormone Delivery

African Journals Online (AJOL)

market for the delivery system and ongoing development of transdermal sprays for hormone ... (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts ... patches and gels have been very popular owing ... This product was developed for ... In a safety announcement, the US Food and.

Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

Directory of Open Access Journals (Sweden)

Sabine Szunerits

2018-02-01

Full Text Available Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs, which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field

Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

Science.gov (United States)

Szunerits, Sabine; Boukherroub, Rabah

2018-01-01

Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field and the handful of

Conductive polymer nanotube patch for fast and controlled ex vivo transdermal drug delivery.

Science.gov (United States)

Nguyen, Thao M; Lee, Sebin; Lee, Sang Bok

2014-10-01

To uptake and release hydrophilic model drugs and insulin in a novel conductive polymer (CP) nanotube transdermal patch. The externally controlled transdermal delivery of model drugs and insulin were tested ex vivo and results were compared with CP films. The unique intrinsic properties of CPs provide electrostatic interaction between the model drugs and polymer backbone. When a pulsed potential was applied, the drug delivery release profile mimics that of injection delivery. With a constant potential applied, the release rate constants of the patch system were up to three-times faster than the control (0 V) and released approximately 80% more drug molecules over 24 h. The CP nanotube transdermal patch represents a new and promising drug method, specifically for hydrophilic molecules, which have been a large obstacle for conventional transdermal drug delivery systems.

Efficacy of a single dose of a transdermal diclofenac patch as pre ...

African Journals Online (AJOL)

Background: We compared the analgesic efficacy of a transdermal diclofenac patch 100 mg (NuPatch® 100, Zydus Cadila, Ahmedabad, India) and intramuscular diclofenac sodium 75 mg (Voveran®, Novartis, India) for postoperative analgesia, and the associated side-effects of the transdermal diclofenac patch. Method: ...

Effect of buprenorphine transdermal patch combined with patientcontrolled intravenous analgesia on the serum pain-related biochemical indexes in elderly patients with intertrochanteric fracture

Directory of Open Access Journals (Sweden)

Lei Xu

2017-09-01

Full Text Available Objective: To study the effect of buprenorphine transdermal patch combined with patientcontrolled intravenous analgesia on the serum pain-related biochemical indexes in elderly patients with intertrochanteric fracture. Methods: A total of 92 elderly patients with intertrochanteric fracture who received surgical treatment in the hospital between August 2014 and January 2017 were collected and divided into control group (n=46 and observation group (n=46 according to the random number table method. The control group received patient-controlled intravenous analgesia, and the observation group received buprenorphine transdermal patch combined with patient-controlled intravenous analgesia. Differences in serum levels of inflammatory factors, oxidative stress indexes and pain mediators of two groups of patients were measured before and 24h after surgery. Results: Differences in serum levels of inflammatory factors, oxidative stress indexes and pain mediators were not statistically significant between the two groups before surgery; 24 h after surgery, serum IL- 1β, IL-6, IL-8, TNF-α, MDA, SP, PGE2, 5-HT, HA and NPY levels of both groups of patients increased significantly while SOD, TAC and CAT levels decreased significantly, and serum IL-1β, IL-6, IL-8, TNF-α, MDA, SP, PGE2, 5-HT, HA and NPY levels of observation group were lower than those of control group while SOD, TAC and CAT levels were higher than those of control group. Conclusion: Buprenorphine transdermal patch combined with patient-controlled intravenous analgesia can effectively inhibit the expression of pain-related indexes and relieve early postoperative pain intensity in elderly patients with intertrochanteric fracture.

Manipulating neuronal activity with low frequency transcranial ultrasound

Science.gov (United States)

Moore, Michele Elizabeth

Stimulation of the rodent cerebral cortex is used to investigate the underlying biological basis for the restorative effects of slow wave sleep. Neuronal activation by optogenetic and ultrasound stimulation elicits changes in action potentials across the cerebral cortex that are recorded as electroencephalograms. Optogenetic stimulation requires an invasive implantation procedure limiting its application in human studies. We sought to determine whether ultrasound stimulation could be as effective as optogenetic techniques currently used, in an effort to further understand the physiological and metabolic requirements of sleep. We successfully recorded electroencephalograms in response to transcranial ultrasound stimulation of the barrel cortex at 1 and 7 Hz frequencies, comparing them to those recorded in response to optogenetic stimuli applied at the same frequencies. Our results showed application of a 473 nm blue LED positioned 6 cm above the skull and ultrasound stimulation at an output voltage of 1000 mVpp produced electroencephalograms with physiological responses of similar amplitude. We concluded that there exists an intensity-proportionate response in the optogenetic stimulation, but not with ultrasound stimulation at the frequencies we surveyed. Activation of neuronal cells in response to optogenetic stimulation in a Thy1-ChR2 transgenic mouse line is specifically targeted to pyramidal cells in the cerebral cortex. ChR2 responses to optogenetic stimulation are mediated by a focal activation of neuronal ion channels. We measured electrophysiological responses to ultrasound stimulation, comparing them to those recorded from optogenetic stimuli. Our results show striking similarities between ultrasound-induced responses and optogenetically-induced responses, which may indicate that transcranial ultrasound stimulation is also mediated by ion channel dependent processes in cerebral cortical neurons. The biophysical substrates for electrical excitability of

Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation

Directory of Open Access Journals (Sweden)

Reshmy Rajan

2011-01-01

Full Text Available Transdermal administration of drugs is generally limited by the barrier function of the skin. Vesicular systems are one of the most controversial methods for transdermal delivery of active substances. The interest in designing transdermal delivery systems was relaunched after the discovery of elastic vesicles like transferosomes, ethosomes, cubosomes, phytosomes, etc. This paper presents the composition, mechanisms of penetration, manufacturing and characterization methods of transferosomes as transdermal delivery systems of active substances. For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport. For the drugs to be delivered to the body, they should cross the membranous barrier. The concept of these delivery systems was designed in an attempt to concentrate the drug in the tissues of interest, while reducing the amount of drug in the remaining tissues. Hence, surrounding tissues are not affected by the drug. In addition, loss of drug does not happen due to localization of drug, leading to get maximum efficacy of the medication. Therefore, the phospholipid based carrier systems are of considerable interest in this era.

Ultrasound-guided drug delivery in cancer

Energy Technology Data Exchange (ETDEWEB)

Chowdhury, Sayan Mullick; Lee, Tae Hwa; Willmann, Jugen K. [Dept. of Radiology, Stanford University School of Medicine, Stanford (United States)

2017-07-15

Recent advancements in ultrasound and microbubble (USMB) mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy.

Interactions of inertial cavitation bubbles with stratum corneum lipid bilayers during low-frequency sonophoresis.

Science.gov (United States)

Tezel, Ahmet; Mitragotri, Samir

2003-12-01

Interactions of acoustic cavitation bubbles with biological tissues play an important role in biomedical applications of ultrasound. Acoustic cavitation plays a particularly important role in enhancing transdermal transport of macromolecules, thereby offering a noninvasive mode of drug delivery (sonophoresis). Ultrasound-enhanced transdermal transport is mediated by inertial cavitation, where collapses of cavitation bubbles microscopically disrupt the lipid bilayers of the stratum corneum. In this study, we describe a theoretical analysis of the interactions of cavitation bubbles with the stratum corneum lipid bilayers. Three modes of bubble-stratum corneum interactions including shock wave emission, microjet penetration into the stratum corneum, and impact of microjet on the stratum corneum are considered. By relating the mechanical effects of these events on the stratum corneum structure, the relationship between the number of cavitation events and collapse pressures with experimentally measured increase in skin permeability was established. Theoretical predictions were compared to experimentally measured parameters of cavitation events.

Therapeutic ultrasound

International Nuclear Information System (INIS)

Crum, Lawrence A

2004-01-01

The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

Transdermal hormone therapy in postmenopausal women: A review of metabolic effects and drug delivery technologies

Directory of Open Access Journals (Sweden)

Nathan W Kopper

2008-10-01

Full Text Available Nathan W Kopper, Jennifer Gudeman, Daniel J ThompsonKV Pharmaceutical, St. Louis, MO, USAAbstract: Vasomotor symptoms (VMS associated with menopause can cause significant discomfort and decrease the quality of life for women in the peri-menopausal and post-menopausal stages of life. Hormone therapy (HT is the mainstay of treatment for menopausal symptoms and is currently the only therapy proven effective for VMS. Numerous HT options are available to treat VMS, including estrogen-only and estrogen-progestogen combination products to meet the needs of both hysterectomized and nonhysterectomized women. In addition to selecting an appropriate estrogen or estrogen-progestogen combination, consideration should be given to the route of administration to best suit the needs of the patient. Delivery systems for hormone therapy include oral tablets, transdermal patches, transdermal topical (nonpatch products, and intravaginal preparations. Oral is currently the most commonly utilized route of administration in the United States. However, evidence suggests that oral delivery may lead to some undesirable physiologic effects caused by significant gut and hepatic metabolism. Transdermal drug delivery may mitigate some of these effects by avoiding gut and hepatic first-pass metabolism. Advantages of transdermal delivery include the ability to administer unmetabolized estradiol directly to the blood stream, administration of lower doses compared to oral products, and minimal stimulation of hepatic protein production. Several estradiol transdermal delivery technologies are available, including various types of patches, topical gels, and a transdermal spray.Keywords: estradiol, hormone therapy, menopause, transdermal drug delivery, vasomotor symptoms

Ultrasound-guided drug delivery in cancer

Directory of Open Access Journals (Sweden)

Sayan Mullick Chowdhury

2017-07-01

Full Text Available Recent advancements in ultrasound and microbubble (USMB mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy.

Results of vardenafil mediated power Doppler ultrasound, contrast enhanced ultrasound and systematic random biopsies to detect prostate cancer.

Science.gov (United States)

Morelli, Girolamo; Pagni, Riccardo; Mariani, Chiara; Minervini, Riccardo; Morelli, Andrea; Gori, Francesco; Ferdeghini, Ezio Maria; Paterni, Marco; Mauro, Eva; Guidi, Elisa; Armillotta, Nicola; Canale, Domenico; Vitti, Paolo; Caramella, Davide; Minervini, Andrea

2011-06-01

We evaluated the ability of the phosphodiesterase-5 inhibitor vardenafil to increase prostate microcirculation during power Doppler ultrasound. We also evaluated the results of contrast and vardenafil enhanced targeted biopsies compared to those of standard 12-core random biopsies to detect cancer. Between May 2008 and January 2010, 150 consecutive patients with prostate specific antigen more than 4 ng/ml at first diagnosis with negative digital rectal examination and transrectal ultrasound, and no clinical history of prostatitis underwent contrast enhanced power Doppler ultrasound (bolus injection of 2.4 ml SonoVue® contrast agent), followed by vardenafil enhanced power Doppler ultrasound (1 hour after oral administration of vardenafil 20 mg). All patients underwent standard 12-core transrectal ultrasound guided random prostate biopsy plus 1 further sampling from each suspected hypervascular lesion detected by contrast and vardenafil enhanced power Doppler ultrasound. Prostate cancer was detected in 44 patients (29.3%). Contrast and vardenafil enhanced power Doppler ultrasound detected suspicious, contrast enhanced and vardenafil enhanced areas in 112 (74.6%) and 110 patients (73.3%), and was diagnostic for cancer in 32 (28.5%) and 42 (38%), respectively. Analysis of standard technique, and contrast and vardenafil enhanced power Doppler ultrasound findings by biopsy core showed significantly higher detection using vardenafil vs contrast enhanced power Doppler ultrasound and standard technique (41.2% vs 22.7% and 8.1%, p power Doppler ultrasound was 10% and 11.7% (p not significant). Vardenafil enhanced power Doppler ultrasound enables excellent visualization of the microvasculature associated with cancer and can improve the detection rate compared to contrast enhanced power Doppler ultrasound and the random technique. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Transdermal granisetron: a guide to its use in preventing nausea and vomiting induced by chemotherapy.

Science.gov (United States)

Keating, Gillian M; Duggan, Sean T; Curran, Monique P

2012-09-01

Transdermal granisetron (Sancuso®) is effective in the prevention of nausea and vomiting in patients with cancer who are receiving moderately or highly emetogenic chemotherapy for 3-5 days. Transdermal granisetron is noninferior to oral granisetron in this indication, and is generally well tolerated in this indication. Thus, transdermal granisetron provides a convenient option for the prevention of chemotherapy-induced nausea and vomiting, with the potential to improve patient compliance.

Transdermal optogenetic peripheral nerve stimulation

Science.gov (United States)

Maimon, Benjamin E.; Zorzos, Anthony N.; Bendell, Rhys; Harding, Alexander; Fahmi, Mina; Srinivasan, Shriya; Calvaresi, Peter; Herr, Hugh M.

2017-06-01

Objective: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks. Approach: Here we report an alternative approach involving transdermal illumination. Utilizing an intramuscular injection of ultra-high concentration AAV6-hSyn-ChR2-EYFP in rats. Main results: We demonstrate transdermal stimulation of motor nerves at 4.4 mm and 1.9 mm depth with an incident laser power of 160 mW and 10 mW, respectively. Furthermore, we employ this technique to accurately control ankle position by modulating laser power or position on the skin surface. Significance: These results have the potential to enable future scientific optogenetic studies of pathologies implicated in the peripheral nervous system for awake, freely-moving animals, as well as a basis for future clinical studies.

Comparative enhancing effects of electret with chemical enhancers on transdermal delivery of meloxicam in vitro

International Nuclear Information System (INIS)

Cui, L L; Hou, X M; Li, G D; Jiang, J; Liang, Y Y; Xin, X

2008-01-01

Electret offers enhancing effect in transdermal drug delivery for altering of the arrangement of lipid molecules in the stratum corneum, forming many transient permeable apertures and enhancing the transdermal drug delivery. In this paper, meloxicam patch formulations were developed to make the comparative study of transdermal drug delivery between electret and chemical enhancers. Patches were made into control, electret, chemical enhancer and electret with chemical enhancer ones, according to the preparation procedure. The electret combined with chemical enhancer patch was designed to probe the incorporation between electret and chemical enhancer in transdermal drug delivery. The meloxicam release from the patch was found to increase in order of blank, chemical enhancer, electret and electret with chemical enhancer patch, in general.

MICRONEEDLES AS A WAY TO INCREASE THE TRANSDERMAL INSULIN DELIVERY

Directory of Open Access Journals (Sweden)

E. G. Kuznetsova

2016-01-01

Full Text Available Aim: to prove the possibility of increasing the diffusion of insulin through the skin in vitro with pre-applying microneedles.Materials and methods. Microemulsion for transdermal therapeutic system of insulin has been used in vitro studies. Genetically engineered human insulin has been used in this research. Applicators with silicon microneedles (40 and 150 microns long have been used to enhance the diffusion fl ux of drug substance. The dynamics of insulin release from the transdermal therapeutic systems through the rabbit skin has been studied in glass Franz diffusion cells in analyzer diffusion of drugs HDT 1000 (Copley Scientifi c Ltd., UK. Insulin has been labeled with fl uorescein isothiocyanate to separate the insulin absorption spectrum from the spectra of native skin proteins at spectrophotometer measurements.Results. The amounts of insulin delivered through the skin in vitro after previous application of microneedles of 40 and 150 microns are 282.5 ± 61.1 and 372.3 ± 7.0 microgram, respectively. This is 1.4 and 1.9 times more than in the transdermal system without microneedles.Conclusion. The conditions for increasing the diffusion of insulin through the skin in a model transdermal therapeutic system with microneedles (length – 150 microns, duration of pre-application – 1 hour have been found.

Formulation, in vitro and in vivo evaluation of transdermal patches containing risperidone.

Science.gov (United States)

Aggarwal, Geeta; Dhawan, Sanju; Hari Kumar, S L

2013-01-01

The efficacy of oral risperidone treatment in prevention of schizophrenia is well known. However, oral side effects and patient compliance is always a problem for schizophrenics. In this study, risperidone was formulated into matrix transdermal patches to overcome these problems. The formulation factors for such patches, including eudragit RL 100 and eudragit RS 100 as matrix forming polymers, olive oil, groundnut oil and jojoba oil in different concentrations as enhancers and amount of drug loaded were investigated. The transdermal patches containing risperidone were prepared by solvent casting method and characterized for physicochemical and in vitro permeation studies through excised rat skin. Among the tested preparations, formulations with 20% risperidone, 3:2 ERL 100 and ERS 100 as polymers, mixture of olive oil and jojoba oil as enhancer, exhibited greatest cumulative amount of drug permeated (1.87 ± 0.09 mg/cm(2)) in 72 h, so batch ROJ was concluded as optimized formulation and assessed for pharmacokinetic, pharmacodynamic and skin irritation potential. The pharmacokinetic characteristics of the optimized risperidone patch were determined using rabbits, while orally administered risperidone in solution was used for comparison. The calculated relative bioavailability of risperidone transdermal patch was 115.20% with prolonged release of drug. Neuroleptic efficacy of transdermal formulation was assessed by rota-rod and grip test in comparison with control and marketed oral formulations with no skin irritation. This suggests the transdermal application of risperidone holds promise for improved bioavailability and better management of schizophrenia in long-term basis.

Accurate evaluation of viscoelasticity of radial artery wall during flow-mediated dilation in ultrasound measurement

Science.gov (United States)

Sakai, Yasumasa; Taki, Hirofumi; Kanai, Hiroshi

2016-07-01

In our previous study, the viscoelasticity of the radial artery wall was estimated to diagnose endothelial dysfunction using a high-frequency (22 MHz) ultrasound device. In the present study, we employed a commercial ultrasound device (7.5 MHz) and estimated the viscoelasticity using arterial pressure and diameter, both of which were measured at the same position. In a phantom experiment, the proposed method successfully estimated the elasticity and viscosity of the phantom with errors of 1.8 and 30.3%, respectively. In an in vivo measurement, the transient change in the viscoelasticity was measured for three healthy subjects during flow-mediated dilation (FMD). The proposed method revealed the softening of the arterial wall originating from the FMD reaction within 100 s after avascularization. These results indicate the high performance of the proposed method in evaluating vascular endothelial function just after avascularization, where the function is difficult to be estimated by a conventional FMD measurement.

Status of surfactants as penetration enhancers in transdermal drug delivery

Directory of Open Access Journals (Sweden)

Iti Som

2012-01-01

Full Text Available Surfactants are found in many existing therapeutic, cosmetic, and agro-chemical preparations. In recent years, surfactants have been employed to enhance the permeation rates of several drugs via transdermal route. The application of transdermal route to a wider range of drugs is limited due to significant barrier to penetration across the skin which is associated with the outermost stratum corneum layer. Surfactants have effects on the permeability characteristics of several biological membranes including skin. They have the potential to solubilize lipids within the stratum corneum. The penetration of the surfactant molecule into the lipid lamellae of the stratum corneum is strongly dependent on the partitioning behavior and solubility of surfactant. Surfactants ranging from hydrophobic agents such as oleic acid to hydrophilic sodium lauryl sulfate have been tested as permeation enhancer to improve drug delivery. This article reviews the status of surfactants as permeation enhancer in transdermal drug delivery of various drugs.

Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review

International Nuclear Information System (INIS)

Tuca, Albert

2009-01-01

Until now only intravenous and oral formulations of 5HT 3 receptor antagonists have been available. Recently a new formulation of a 5HT 3 receptor antagonist, transdermal granisetron, has been developed, and approved by the FDA. Three phase I studies to evaluate its pharmacokinetic profile have shown that granisetron administered by a transdermal delivery system is absorbed by passive diffusion and maximal concentration is reached 48 hours after patch application. The patch of 52 cm 2 , which contains 34.3 mg of granisetron, releases 3.3 mg of the drug every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6 days, similar to levels obtained with 2 mg of oral granisetron, administered every day during the same period of time. Two randomized as yet unpublished clinical trials (phase II/III) have been conducted to evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting, in patients receiving moderately and highly emetogenic chemotherapy, compared with 2 mg of oral granisetron. More than 800 cancer patients were included in the trials. The rate of complete control of acute emesis was 49% for the phase II trial and 60% for the phase III trial. Neither trial showed a statistically significant difference between transdermal and oral granisetron. The control of delayed emesis was observed in 46% of patients, and there were no statistically significant differences between transdermal and oral granisetron. The most common adverse effects in both trials were constipation (<7%) and headache (<1%); there were no statistically significant differences between transdermal and oral granisetron. These data show that transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with both moderate and high emetogenic potential. Efficacy and safety of transdermal granisetron are fully comparable with that of oral granisetron. More clinical trials using regimens of 2 or 3 drugs

Topical and transdermal drug delivery: principles and practice

National Research Council Canada - National Science Library

Benson, Heather A. E; Watkinson, Adam C

2012-01-01

.... Providing an overview of the current science in drug and cosmetic application to and through the skin, Topical and Transdermal Drug Delivery includes treatment of skin conditions, skin permeation...

Enhanced Transdermal Permeability via Constructing the Porous Structure of Poloxamer-Based Hydrogel

Directory of Open Access Journals (Sweden)

Wen-Yi Wang

2016-11-01

Full Text Available A major concern for transdermal drug delivery systems is the low bioavailability of targeted drugs primarily caused by the skin’s barrier function. The resistance to the carrier matrix for the diffusion and transport of drugs, however, is routinely ignored. This study reports a promising and attractive approach to reducing the resistance to drug transport in the carrier matrix, to enhance drug permeability and bioavailability via enhanced concentration-gradient of the driving force for transdermal purposes. This approach simply optimizes and reconstructs the porous channel structure of the carrier matrix, namely, poloxamer 407 (P407-based hydrogel matrix blended with carboxymethyl cellulose sodium (CMCs. Addition of CMCs was found to distinctly improve the porous structure of the P407 matrix. The pore size approximated to normal distribution as CMCs were added and the fraction of pore number was increased by over tenfold. Transdermal studies showed that P407/CMCs saw a significant increase in drug permeability across the skin. This suggests that P407/CMC with improved porous structure exhibits a feasible and promising way for the development of transdermal therapy with high permeability and bioavailability, thereby avoiding or reducing use of any chemical enhancers.

Transdermal rivastigmine: management of cutaneous adverse events and review of the literature.

Science.gov (United States)

Greenspoon, Jill; Herrmann, Nathan; Adam, David N

2011-07-01

Alzheimer's disease is a chronic neurodegenerative disorder resulting in part from the degeneration of cholinergic neurons in the brain. Rivastigmine, a cholinesterase inhibitor, is commonly used as a treatment for dementia due to its ability to moderate cholinergic neurotransmission; however, treatment with oral rivastigmine can lead to gastrointestinal adverse effects such as nausea and vomiting. Transdermal administration of rivastigmine can minimize these adverse effects by providing continuous delivery of the medication, while maintaining the effectiveness of the oral treatment. While the transdermal form of rivastigmine has been found to have fewer systemic adverse effects compared with the oral form, cutaneous reactions, such as contact dermatitis, can lead to discontinuation of the drug in its transdermal form. Lack of patient compliance with regard to applying the patch to the designated site, applying the patch for the correct length of time or rotating patch application sites increases the risk of cutaneous adverse reactions. This article outlines the diagnosis and management of irritant contact dermatitis and allergic contact dermatitis secondary to transdermal rivastigmine. The large majority of reactions to transdermal patches are of an irritant type, which can be diagnosed clinically by the presence of a pruritic, erythematous, eczematous plaque strictly confined to the borders of the patch. In contrast, an allergic reaction can be differentiated by the presence of vesicles and/or oedema, erythema beyond the boundaries of the transdermal patch and lack of improvement of the lesion 48 hours after removal of the offending treatment. By encouraging the patient to follow a regular rotation schedule for the patch, and using lipid-based emollients for irritant dermatitis and pre- and post-treatment topical corticosteroids for allergic dermatitis, cutaneous reactions can often be alleviated and patients can continue with their medication regimen. Other

Metabolic approaches to enhance transdermal drug delivery. 1. Effect of lipid synthesis inhibitors.

Science.gov (United States)

Tsai, J C; Guy, R H; Thornfeldt, C R; Gao, W N; Feingold, K R; Elias, P M

1996-06-01

The intercellular domains of the stratum corneum, which contain a mixture of cholesterol, free fatty acids, and ceramides, mediate both the epidermal permeability barrier and the transdermal delivery of both lipophilic and hydrophilic molecules. Prior studies have shown that each of the three key lipid classes is required for normal barrier function. For example, selective inhibition of either cholesterol, fatty acid, or ceramide synthesis in the epidermis delays barrier recovery rates after barrier perturbation of hairless mouse skin in vivo. In this study, we investigated the potential of certain inhibitors of lipid synthesis to enhance the transdermal delivery of lidocaine or caffeine as a result of their capacity to perturb barrier homeostasis. After acetone disruption of the barrier, the extent of lidocaine delivery and the degree of altered barrier function paralleled each other. Moreover, the further alteration in barrier function produced by either the fatty acid synthesis inhibitor 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), the cholesterol synthesis inhibitor fluvastatin (FLU), or cholesterol sulfate (CS) resulted in a further increase in lidocaine absorption. Furthermore, coapplications of TOFA and CS together caused an additive increase in lidocaine uptake. Finally, a comparable increase in drug delivery occurred when the barrier was disrupted initially with DMSO instead of acetone; coapplications of TOFA and FLU together again delayed barrier recovery and increased drug delivery by about 8-fold vs delivery from a standard enhancing vehicle. Whereas these metabolic inhibitors also variably increased the octanol/water partitioning of the drugs studied (perhaps via complexion or pH alterations), physicochemical effects of the inhibitors alone did not alter drug uptake in intact skin; i.e., passive mechanisms alone cannot account for the net increase in drug delivery. Our results show that modulations of epidermal lipid biosynthesis, following

Synthesis and characterization of modified starch/polybutadiene as novel transdermal drug delivery system.

Science.gov (United States)

Saboktakin, Mohammad Reza; Akhyari, Shahab; Nasirov, Fizuli A

2014-08-01

Transdermal drug delivery systems are topically administered medicaments in the form of patches that deliver drugs for systemic effects at a predetermined and controlled rate. It works very simply in which drug is applied inside the patch and it is worn on skin for long period of time. Polymer matrix, drug, permeation enhancers are the main components of transdermal drug delivery systems. The objective of the present study was to develop the modified starch and 1,4-cis polybutadiene nanoparticles as novel polymer matrix system. We have been studied the properties of a novel transdermal drug delivery system with clonidine as drug model. Copyright © 2014 Elsevier B.V. All rights reserved.

Optimization of Biopolymer Based Transdermal Films of Metoclopramide as an Alternative Delivery Approach

Directory of Open Access Journals (Sweden)

Betül Aktar

2014-05-01

Full Text Available The objectives of this study were to develop and to characterize sodium alginate based matrix-type transdermal films of metoclopramide hydrochloride (MTC in order to improve patient compliance to treatment. The suitability of sodium alginate was shown to be a natural film former in terms of the physicochemical, mechanical, and bioadhesive features of the MTC loaded transdermal films. Terpinolene provided the highest drug release among the different terpenes (nerolidol, eucalyptol, dl-limonene, or terpinolene assessed as enhancer. Attenuated Total Reflectance Infrared (ATR-FTIR spectroscopy analysis performed to evaluate the effect of the transdermal films on skin barrier confirmed enhancer induced lipid bilayer disruption in stratum corneum, indicating its permeation enhancement effect.

Tracking of cell nuclei for assessment of in vitro uptake kinetics in ultrasound-mediated drug delivery using fibered confocal fluorescence microscopy.

Science.gov (United States)

Derieppe, Marc; de Senneville, Baudouin Denis; Kuijf, Hugo; Moonen, Chrit; Bos, Clemens

2014-10-01

Previously, we demonstrated the feasibility to monitor ultrasound-mediated uptake of a cell-impermeable model drug in real time with fibered confocal fluorescence microscopy. Here, we present a complete post-processing methodology, which corrects for cell displacements, to improve the accuracy of pharmacokinetic parameter estimation. Nucleus detection was performed based on the radial symmetry transform algorithm. Cell tracking used an iterative closest point approach. Pharmacokinetic parameters were calculated by fitting a two-compartment model to the time-intensity curves of individual cells. Cells were tracked successfully, improving time-intensity curve accuracy and pharmacokinetic parameter estimation. With tracking, 93 % of the 370 nuclei showed a fluorescence signal variation that was well-described by a two-compartment model. In addition, parameter distributions were narrower, thus increasing precision. Dedicated image analysis was implemented and enabled studying ultrasound-mediated model drug uptake kinetics in hundreds of cells per experiment, using fiber-based confocal fluorescence microscopy.

Recent trends in the transdermal delivery of therapeutic agents used for the management of neurodegenerative diseases.

Science.gov (United States)

Ita, Kevin

2017-06-01

With the increasing proportion of the global geriatric population, it becomes obvious that neurodegenerative diseases will become more widespread. From an epidemiological standpoint, it is necessary to develop new therapeutic agents for the management of Alzheimer's disease, Parkinson's disease, multiple sclerosis and other neurodegenerative disorders. An important approach in this regard involves the use of the transdermal route. With transdermal drug delivery systems (TDDS), it is possible to modulate the pharmacokinetic profiles of these medications and improve patient compliance. Transdermal drug delivery has also been shown to be useful for drugs with short half-life and low or unpredictable bioavailability. In this review, several transdermal drug delivery enhancement technologies are being discussed in relation to the delivery of medications used for the management of neurodegenerative disorders.

Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review

Directory of Open Access Journals (Sweden)

Albert Tuca

2009-12-01

Full Text Available Albert TucaPalliative Care Hospital Team, Palliative Care Department, Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, SpainAbstract: Until now only intravenous and oral formulations of 5HT3 receptor antagonists have been available. Recently a new formulation of a 5HT3 receptor antagonist, transdermal granisetron, has been developed, and approved by the FDA. Three phase I studies to evaluate its pharmacokinetic profile have shown that granisetron administered by a transdermal delivery system is absorbed by passive diffusion and maximal concentration is reached 48 hours after patch application. The patch of 52 cm2, which contains 34.3 mg of granisetron, releases 3.3 mg of the drug every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6 days, similar to levels obtained with 2 mg of oral granisetron, administered every day during the same period of time. Two randomized as yet unpublished clinical trials (phase II/III have been conducted to evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting, in patients receiving moderately and highly emetogenic chemotherapy, compared with 2 mg of oral granisetron. More than 800 cancer patients were included in the trials. The rate of complete control of acute emesis was 49% for the phase II trial and 60% for the phase III trial. Neither trial showed a statistically significant difference between transdermal and oral granisetron. The control of delayed emesis was observed in 46% of patients, and there were no statistically significant differences between transdermal and oral granisetron. The most common adverse effects in both trials were constipation (<7% and headache (<1%; there were no statistically significant differences between transdermal and oral granisetron. These data show that transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with both moderate and high

Turning theory into practice: the development of modern transdermal drug delivery systems and future trends.

Science.gov (United States)

Perumal, O; Murthy, S N; Kalia, Y N

2013-01-01

Despite its remarkable barrier function, the skin remains an attractive site for systemic drug delivery given its easy accessibility, large surface area and the possibility to bypass the gastrointestinal tract and the liver and so modify drug absorption kinetics. The pioneering work of Scheuplein, Higuchi and others in the 1960s helped to explain the processes involved in passive percutaneous absorption and led to the development of mathematical models to describe transdermal drug delivery. The intervening years have seen these theories turned to practice and a significant number of transdermal systems are now available including some that employ active drug delivery. This review briefly discusses the evolution of transdermal therapeutic systems over the years and the potential of newer transdermal technologies to deliver hydrophilic drugs and macromolecules through the skin. © 2013 S. Karger AG, Basel.

Transport efficiency in transdermal drug delivery: What is the role of fluid microstructure?

Science.gov (United States)

Liuzzi, Roberta; Carciati, Antonio; Guido, Stefano; Caserta, Sergio

2016-03-01

Interaction of microstructured fluids with skin is ubiquitous in everyday life, from the use of cosmetics, lotions, and drugs, to personal care with detergents or soaps. The formulation of microstructured fluids is crucial for the control of the transdermal transport. In biomedical applications transdermal delivery is an efficient approach, alternative to traditional routes like oral and parenteral administration, for local release of drugs. Poor skin permeability, mainly due to its outer layer, which acts as the first barrier against the entry of external compounds, greatly limits the applicability of transdermal delivery. In this review, we focus on recent studies on the improvement of skin transport efficiency by using microemulsions (ME). Quantitative techniques, which are able to investigate both skin morphology and penetration processes, are also reviewed. ME are increasingly used as transdermal systems due to their low preparation cost, stability and high bioavailability. ME may act as penetration enhancers for many active principles, but ME microstructure should be chosen appropriately considering several factors such as ratio and type of ingredients and physic-chemical properties of the active components. ME microstructure is strongly affected by the flow conditions applied during processing, or during spreading and rubbing onto skin. Although the role played by ME microstructure has been generally recognized, the skin transport mechanisms associated with different ME microstructures are still to be elucidated and further investigations are required to fully exploit the potential of ME in transdermal delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Transcranial cavitation-mediated ultrasound therapy at sub-MHz frequency via temporal interference modulation

Science.gov (United States)

Sun, Tao; Sutton, Jonathan T.; Power, Chanikarn; Zhang, Yongzhi; Miller, Eric L.; McDannold, Nathan J.

2017-10-01

Sub-megahertz transmission is not usually adopted in pre-clinical small animal experiments for focused ultrasound (FUS) brain therapy due to the large focal size. However, low frequency FUS is vital for preclinical evaluations due to the frequency-dependence of cavitation behavior. To maximize clinical relevance, a dual-aperture FUS system was designed for low-frequency (274.3 kHz) cavitation-mediated FUS therapy. Combining two spherically curved transducers provides significantly improved focusing in the axial direction while yielding an interference pattern with strong side lobes, leading to inhomogeneously distributed cavitation activities. By operating the two transducers at slightly offset frequencies to modulate this interference pattern over the period of sonication, the acoustic energy was redistributed and resulted in a spatially homogenous treatment profile. Simulation and pressure field measurements in water were performed to assess the beam profiles. In addition, the system performance was demonstrated in vivo in rats via drug delivery through microbubble-mediated blood-brain barrier disruption. This design resulted in a homogenous treatment profile that was fully contained within the rat brain at a clinically relevant acoustic frequency.

Ultrasound Mediated Microbubbles Destruction Augmented Sonolysis: An In Vitro and In Vivo Study

Directory of Open Access Journals (Sweden)

Hai Cui

2017-01-01

Full Text Available Objective. This study was aimed at exploring ultrasound mediated microbubbles destruction (UMMD assisted sonolysis in both the in vitro and in vivo clots. Methods. Therapeutic ultrasound (TUS and lipid microbubbles (MBs were used in whole blood clots and divided into the control, TUS group, and TUS + MB group. Thrombolytic rates and microscopy were performed. Color Doppler flow imaging (CDFI and angiography were performed to evaluate the recanalization rates and flow scores in femoral arterial thrombus (FAT in rabbits. FAT were dyed with H&E. Results. The average thrombolytic ratios of TUS + MB group were significantly higher than those of TUS group and the control group (both P<0.05. Clots had different pathological changes. Recanalization rates and flow scores in TUS + MB group were significantly higher than the control and TUS group. Flow scores and recanalization ratios were grade 0 in 0% of the control group, grade I in 25% of TUS group, and grade II or higher in 87.5% of TUS + MB group after 30 min sonolysis. Conclusions. Both the in vitro and in vivo sonolysis can be significantly augmented by the introduction of MBs without thrombolytic agents, which might be induced by the enhanced cavitation via UMMD.

Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret.

Science.gov (United States)

Tu, Ye; Wang, Xinxia; Lu, Ying; Zhang, He; Yu, Yuan; Chen, Yan; Liu, Junjie; Sun, Zhiguo; Cui, Lili; Gao, Jing; Zhong, Yanqiang

We recently reported that electret, which was prepared by a corona charging system with polypropylene film, could enhance the transdermal delivery of several drugs of low molecular weight. The aim of this study was to investigate whether electret could enhance the transdermal delivery of protein drugs by N -trimethyl chitosan nanoparticles (TMC NPs) prepared by an ionic gelation method. A series of experiments were performed, including in vitro skin permeation assays and anti-inflammatory effects, to evaluate the transdermal delivery of protein drugs by TMC NPs in the presence of electret. The results showed that in the presence of electret, the transdermal delivery of protein drugs in TMC NPs was significantly enhanced, as demonstrated by in vitro permeation studies and confocal laser scanning microscopy. Notably, superoxide dismutase-loaded TMC NPs combined with electret exhibited the best inhibitory effect on the edema of the mouse ear. TMC NPs combined with electret represent a novel platform for the transdermal delivery of protein drugs.

[11C]diclofenac sodium: synthesis and PET assessment of transdermal penetration

International Nuclear Information System (INIS)

Petroni, Debora; Menichetti, Luca; Sorace, Oreste; Poli, Michela; Vanasia, Massimo; Salvadori, Piero A.

2011-01-01

The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) imaging as a new tool to detect transdermal penetration of topical drugs in human subjects. The compound used in the study is sodium 2-[(2,6-dichlorophenyl)amino]phenyl]acetate, better known as diclofenac sodium. This molecule belongs to the family of non-steroidal anti-inflammatory drugs and is considered one of the first choices among non-steroidal anti-inflammatory drugs for the treatment of inflammatory diseases; it is widely used and commercially present in a large number of pharmaceutical forms and formulations. 11 C-labeled diclofenac has been synthesized and coformulated, as an internal indicator, with a proprietary preparation based on the use of a sprayer. The radiolabeled preparation was topically administered to healthy volunteers, and PET imaging was used to evaluate transdermal penetration. Results obtained have demonstrated the efficacy of PET and radiolabeled tracers for the evaluation of transdermal penetration of active pharmaceutical ingredients as topical formulations.

Protection against soman and sarin exposure by transdermal physostigmine and scopolamine

Energy Technology Data Exchange (ETDEWEB)

Meshulam, Y.; Davidovici, R.; Levy, A.

1993-05-13

The purpose of this study was to evaluate the prophylactic efficacy of physostigmine (physo), administered via sustained release (SR) methods, with and without scopolamine, against soman and sarin exposure in guinea-pigs. Transdermal physo pad (3 sq cm/kg; 60-80 ug/sq cm), containing a vehicle based on propionic acid, was applied onto the dorsal back of the animals, 24 hours before exposure to the cholinesterase (ChE) inhibitors. At the time of exposure, physo concentrations in brain and plasma were 3.6 ng/g and 4.1 ng/ml respectively. Brain and whole blood ChE activity were inhibited to 70% and 57% of their original activity. Transdermal physo by itself protected up to 70% of the animals exposed to 1.5 LD(50) of soman or sarin (100% mortality was recorded in the control group). Combining transdermal physo with Scopoderm (by Ciba Geigy Inc.) provided full protection against 1.5 LD(50).

Treatment of Severe Cancer Pain by Transdermal Fentanyl

Directory of Open Access Journals (Sweden)

Dženita Ljuca

2010-05-01

Full Text Available The goal of research was to determine the frequency, intensity, time of occurrence, duration and causes of breakthrough pain (BTP in patients whose carcinoma pain was treated by transdermal fentanyl. (TDF. A prospective study was conducted in a hospice for recumbent patients of the Centre for Palliative Care (hospice University Clinical Centre Tuzla from October 2009 to December 2010. 33 patients in terminal stage of carcinoma, who had been treated by transdermal fentanyl due to their excruciating pain (7-10 mark on numerica! scale with initial dosage of 25 μg as a strong opiate analgesic, were monitored within the time period of 10 days. In the statistics we used the even T - test, the Wilcox test and Mann -Whitney test. The difference was seen to be significant at p < 0,05. Treatment by transdermal fentanyl significantly reduces the intensity of strong carcinoma pain (p < 0.0001, with a frequent requirement for dose increase with bone metastasis. The intensity of BTP is higher compared to the pain experienced upon reception. The frequency and intensity of BTP are significantly reduced already in the second day of treatment by transdermal fentanyl (p = 0,0024. The BTP is most intense in patients with neck and head tumours (9,26 ± 0,66, and most frequent with abdomen and pelvic tumour. The biggest number of BTP (68.3 % occurs within first three days of treatment. BTP most frequently occurs in the evening or at night (between 18:00 and 06:00 h in 62,2 % of the cases, with the duration of usually less than 15 minutes (65,2% of the cases. In 61,6 % cases the occurrence of BTP is related to physical activities or psychosocial incidents, while the cause is undetermined in 38,4 % of examinees.BTP is most frequent within first three days of treatment by TDF. Using the optimal dosage a good control of carcinoma pain is enabled, regardless of the occurrence of bone metastasis, while it also helps reduce the frequency and intensity of BTP.

Transdermal delivery of isoniazid and rifampin in guinea pigs by electro-phonophoresis.

Science.gov (United States)

Chen, Suting; Han, Yi; Yu, Daping; Huo, Fengmin; Wang, Fen; Li, Yunxu; Dong, Lingling; Liu, Zhidong; Huang, Hairong

2017-11-01

Electro-phonophoresis (EP) has been used as a drug delivery approach in clinical fields. The objective of the present study is to evaluate the skin permeability of isoniazid and rifampin in guinea pigs by EP to provide reference basis for clinical applications of such transdermal delivery system in the treatment of patients with superficial tuberculosis. Isoniazid and rifampin solutions were delivered transdermally with or without EP in health guinea pigs for 0.5 h. Local skin and blood samples were collected serially at 0, 1/2, 1, 2, 4, 6 and 24 h after dosing. Drug concentrations in local skin and blood were evaluated by high-performance liquid chromatography. Isoniazid concentrations in local skin of guinea pigs receiving isoniazid through EP transdermal delivery were significantly higher than in animals receiving only isoniazid with transdermal patch. However, for rifampin, patches alone group presented almost uniform concentration versus time curve with that of EP group, and both groups had concentrations much higher than the therapeutic concentration of the drug over sustainable time. After EP transdermal delivery, the mean peak concentrations of isoniazid and rifampin in skin were 771.0 ± 163.4 μg/mL and 81.2 ± 17.3 μg/mL respectively. Neither isoniazid nor rifampin concentration in blood could be detected (below the lower detection limit of 1 μg/mL) at any time point. The present study showed that application of EP significantly enhanced INH penetration through skin in guinea pigs, while RIF patch alone obtained therapeutic concentration in local skin. Our work suggests several possible medication approaches for efficient treatment of superficial tuberculosis.

Functionalization of Cotton Fabrics with Polycaprolactone Nanoparticles for Transdermal Release of Melatonin

Directory of Open Access Journals (Sweden)

Daniele Massella

2017-12-01

Full Text Available Drug delivery by means of transdermal patches raised great interest as a non-invasive and sustained therapy. The present research aimed to design a patch for transdermal delivery of melatonin, which was encapsulated in polycaprolactone (PCL nanoparticles (NPs by employing flash nanoprecipitation (FNP technique. Melatonin-loaded PCL nanoparticles were successfully prepared with precise control of the particle size by effectively tuning process parameters. The effect of process parameters on the particle size was assessed by dynamic light scattering for producing particles with suitable size for transdermal applications. Quantification of encapsulated melatonin was performed by mean of UV spectrophotometry, obtaining the estimation of encapsulation efficiency (EE% and loading capacity (LC%. An EE% higher than 80% was obtained. Differential scanning calorimetry (DSC analysis of NPs was performed to confirm effective encapsulation in the solid phase. Cotton fabrics, functionalized by imbibition with the nano-suspension, were analyzed by scanning electron microscopy to check morphology, adhesion and distribution of the NPs on the surface; melatonin transdermal release from the functionalized fabric was performed via Franz’s cells by using a synthetic membrane. NPs were uniformly distributed on cotton fibres, as confirmed by SEM observations; the release test showed a continuous and controlled release whose kinetics were satisfactorily described by Baker–Lonsdale model.

Single-transducer dual-frequency ultrasound generation to enhance acoustic cavitation.

Science.gov (United States)

Liu, Hao-Li; Hsieh, Chao-Ming

2009-03-01

Dual- or multiple-frequency ultrasound stimulation is capable of effectively enhancing the acoustic cavitation effect over single-frequency ultrasound. Potential application of this sonoreactor design has been widely proposed such as on sonoluminescence, sonochemistry enhancement, and transdermal drug release enhancement. All currently available sonoreactor designs employed multiple piezoelectric transducers for generating single-frequency ultrasonic waves separately and then these waves were mixed and interfered in solutions. The purpose of this research is to propose a novel design of generating dual-frequency ultrasonic waves with single piezoelectric elements, thereby enhancing acoustic cavitation. Macroscopic bubbles were detected optically, and they were quantified at either a single-frequency or for different frequency combinations for determining their efficiency for enhancing acoustic cavitation. Visible bubbles were optically detected and hydrogen peroxide was measured to quantify acoustic cavitation. Test water samples with different gas concentrations and different power levels were used to determine the efficacy of enhancing acoustic cavitation of this design. The spectrum obtained from the backscattered signals was also recorded and examined to confirm the occurrence of stable cavitation. The results confirmed that single-element dual-frequency ultrasound stimulation can enhance acoustic cavitation. Under certain testing conditions, the generation of bubbles can be enhanced up to a level of five times higher than the generation of bubbles in single-frequency stimulation, and can increase the hydrogen peroxide production up to an increase of one fold. This design may serve as a useful alternative for future sonoreactor design owing to its simplicity to produce dual- or multiple-frequency ultrasound.

Modular reservoir concept for MEMS-based transdermal drug delivery systems

International Nuclear Information System (INIS)

Cantwell, Cara T; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P

2014-01-01

While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management. (technical note)

Modular reservoir concept for MEMS-based transdermal drug delivery systems

Science.gov (United States)

Cantwell, Cara T.; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P.

2014-11-01

While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management.

Biomaterials as novel penetration enhancers for transdermal and dermal drug delivery systems.

Science.gov (United States)

Chen, Yang; Wang, Manli; Fang, Liang

2013-01-01

The highly organized structure of the stratum corneum provides an effective barrier to the drug delivery into or across the skin. To overcome this barrier function, penetration enhancers are always used in the transdermal and dermal drug delivery systems. However, the conventional chemical enhancers are often limited by their inability to delivery large and hydrophilic molecules, and few to date have been routinely incorporated into the transdermal formulations due to their incompatibility and local irritation issues. Therefore, there has been a search for the compounds that exhibit broad enhancing activity for more drugs without producing much irritation. More recently, the use of biomaterials has emerged as a novel method to increase the skin permeability. In this paper, we present an overview of the investigations on the feasibility and application of biomaterials as penetration enhancers for transdermal or dermal drug delivery systems.

Transdermal administration of radiolabelled [14C]rotigotine by a patch formulation: A mass balance trial

NARCIS (Netherlands)

Cawello, W.; Wolff, H.M.; Meuling, W.J.A.; Horstmann, R.; Braun, M.

2007-01-01

Background and objective: The dopamine agonist rotigotine has been formulated in a silicone-based transdermal system for once-daily administration. The objective of the present study was to characterise the mass balance of rotigotine in humans after administration of a single transdermal patch

Hybrid electrospun chitosan-phospholipids nanofibers for transdermal drug delivery

DEFF Research Database (Denmark)

Mendes, Ana Carina Loureiro; Gorzelanny, Christian; Halter, Natalia

2016-01-01

Chitosan (Ch) polysaccharide was mixed with phospholipids (P) to generate electrospun hybrid nanofibers intended to be used as platforms for transdermal drug delivery. Ch/P nanofibers exibithed average diameters ranging from 248 +/- 94 nm to 600 +/- 201 nm, depending on the amount of phospholipids...... used. Fourier Transformed Infra-Red (FTIR) spectroscopy and Dynamic Light Scattering (DLS) data suggested the occurrence of electrostatic interactions between amine groups of chitosan with the phospholipid counterparts. The nanofibers were shown to be stable for at least 7 days in Phosphate Buffer...... culture plate (control). The release of curcumin, diclofenac and vitamin B12, as model drugs, from Ch/P hybrid nanofibers was investigated, demonstrating their potential utilization as a transdermal drug delivery system....

Penetration Enhancement Effect of Turpentine Oil on Transdermal ...

African Journals Online (AJOL)

inflammation drastically affect the quality of life after SCI. ... inhibitors may reduce spinal cord ischemic injury. [11]. Various .... Healthy male Wistar rats (200-250 g) were used ..... Guy RH. Transdermal science and technology an update.

Anti-cancer vaccination by transdermal delivery of antigen peptide-loaded nanogels via iontophoresis.

Science.gov (United States)

Toyoda, Mao; Hama, Susumu; Ikeda, Yutaka; Nagasaki, Yukio; Kogure, Kentaro

2015-04-10

Transdermal vaccination with cancer antigens is expected to become a useful anti-cancer therapy. However, it is difficult to accumulate enough antigen in the epidermis for effective exposure to Langerhans cells because of diffusion into the skin and muscle. Carriers, such as liposomes and nanoparticles, may be useful for the prevention of antigen diffusion. Iontophoresis, via application of a small electric current, is a noninvasive and efficient technology for transdermal drug delivery. Previously, we succeeded in the iontophoretic transdermal delivery of liposomes encapsulating insulin, and accumulation of polymer-based nanoparticle nanogels in the stratum corneum of the skin. Therefore, in the present study, we examined the use of iontophoresis with cancer antigen gp-100 peptide KVPRNQDWL-loaded nanogels for anti-cancer vaccination. Iontophoresis resulted in the accumulation of gp-100 peptide and nanogels in the epidermis, and subsequent increase in the number of Langerhans cells in the epidermis. Moreover, tumor growth was significantly suppressed by iontophoresis of the antigen peptide-loaded nanogels. Thus, iontophoresis of the antigen peptide-loaded nanogels may serve as an effective transdermal delivery system for anti-cancer vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

Microneedles array with biodegradable tips for transdermal drug delivery

Science.gov (United States)

Iliescu, Ciprian; Chen, Bangtao; Wei, Jiashen; Tay, Francis E. H.

2008-12-01

The paper presented an enhancement solution for transdermal drug delivery using microneedles array with biodegradable tips. The microneedles array was fabricated by using deep reactive ion etching (DRIE) and the biodegradable tips were made to be porous by electrochemical etching process. The porous silicon microneedle tips can greatly enhance the transdermal drug delivery in a minimum invasion, painless, and convenient manner, at the same time; they are breakable and biodegradable. Basically, the main problem of the silicon microneedles consists of broken microneedles tips during the insertion. The solution proposed is to fabricate the microneedle tip from a biodegradable material - porous silicon. The silicon microneedles are fabricated using DRIE notching effect of reflected charges on mask. The process overcomes the difficulty in the undercut control of the tips during the classical isotropic silicon etching process. When the silicon tips were formed, the porous tips were then generated using a classical electrochemical anodization process in MeCN/HF/H2O solution. The paper presents the experimental results of in vitro release of calcein and BSA with animal skins using a microneedle array with biodegradable tips. Compared to the transdermal drug delivery without any enhancer, the microneedle array had presented significant enhancement of drug release.

Natural oils as skin permeation enhancers for transdermal delivery of olanzapine: in vitro and in vivo evaluation.

Science.gov (United States)

Aggarwal, Geeta; Dhawan, Sanju; HariKumar, S L

2012-03-01

The feasibility of development of transdermal delivery system of olanzapine utilizing natural oils as permeation enhancers was investigated. Penetration enhancing potential of corn (maize) oil, groundnut oil and jojoba oil on in vitro permeation of olanzapine across rat skin was studied. The magnitude of flux enhancement factor with corn oil, groundnut oil and jojoba oil was 7.06, 5.31 and 1.9 respectively at 5mg/ml concentration in solvent system. On the basis of in vitro permeation studies, eudragit based matrix type transdermal patches of olanzapine were fabricated using optimized concentrations of natural oils as permeation enhancers. All transdermal patches were found to be uniform with respect to physical characteristics. The interaction studies carried out by comparing the results of ultraviolet, HPLC and FTIR analyses for the pure drug, polymers and mixture of drug and polymers indicated no chemical interaction between the drug and excipients. Corn oil containing unsaturated fatty acids was found to be promising natural permeation enhancer for transdermal delivery of olanzapine with greatest cumulative amount of drug permeated (1010.68 μg/cm²/h) up to 24 h and caused no skin irritation. The fabricated transdermal patches were found to be stable. The pharmacokinetic characteristics of the final optimized matrix patch (T2) were determined after transdermal application to rabbits. The calculated relative bioavailability of TDDS was 113.6 % as compared to oral administration of olanzapine. The therapeutic effectiveness of optimized transdermal system was confirmed by tranquillizing activity in rotarod and grip mice model.

A REVIEW OF LOW-INTENSITY ULTRASOUND FOR CANCER THERAPY

Science.gov (United States)

WOOD, ANDREW K. W.; SEHGAL, CHANDRA M.

2015-01-01

The literature describing the use of low-intensity ultrasound in four major areas of cancer therapy was reviewed - sonodynamic therapy, ultrasound mediated chemotherapy, ultrasound mediated gene delivery and antivascular ultrasound therapy. Each technique consistently resulted in the death of cancer cells and the bioeffects of ultrasound were primarily attributed to thermal actions and inertial cavitation. In each therapeutic modality, theranostic contrast agents composed of microbubbles played a role in both therapy and vascular imaging. The development of these agents is important as it establishes a therapeutic-diagnostic platform which can monitor the success of anti-cancer therapy. Little attention, however, has been given to either the direct assessment of the underlying mechanisms of the observed bioeffects or to the viability of these therapies in naturally occurring cancers in larger mammals; if such investigations provided encouraging data there could be a prompt application of a therapy technique in treating cancer patients. PMID:25728459

Preparation and characterization of metoprolol tartrate containing matrix type transdermal drug delivery system.

Science.gov (United States)

Malipeddi, Venkata Ramana; Awasthi, Rajendra; Ghisleni, Daniela Dal Molim; de Souza Braga, Marina; Kikuchi, Irene Satiko; de Jesus Andreoli Pinto, Terezinha; Dua, Kamal

2017-02-01

The present study aimed to develop matrix-type transdermal drug delivery system (TDDS) of metoprolol tartrate using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA). The transdermal films were evaluated for physical parameters, Fourier transform infrared spectroscopy analysis (FTIR), differential scanning calorimetry (DSC), in vitro drug release, in vitro skin permeability, skin irritation test and stability studies. The films were found to be tough, non-sticky, easily moldable and possess good tensile strength. As the concentration of PVA was increased, the tensile strength of the films was also increased. Results of FTIR spectroscopy and DSC revealed the absence of any drug-polymer interactions. In vitro release of metoprolol followed zero-order kinetics and the mechanism of release was found to be diffusion rate controlled. In vitro release studies of metoprolol using Keshary-Chein (vertical diffusion cell) indicated 65.5 % drug was released in 24 h. In vitro skin permeation of metoprolol transdermal films showed 58.13 % of the drug was released after 24 h. In vitro skin permeation of metoprolol followed zero-order kinetics in selected formulations. The mechanism of release was found to be diffusion rate controlled. In a 22-day skin irritation test, tested formulation of transdermal films did not exhibit any allergic reactions, inflammation, or contact dermatitis. The transdermal films showed good stability in the 180-day stability study. It can be concluded that the TDDS of MPT can help in bypassing the first-pass effect and will provide patient improved compliance, without sacrificing the therapeutic advantages of the drugs.

Transdermal and transbuccal drug delivery systems: enhancement using iontophoretic and chemical approaches.

Science.gov (United States)

Hu, Longsheng; Silva, Sérgio M C; Damaj, Bassam B; Martin, Richard; Michniak-Kohn, Bozena B

2011-12-12

We investigated the enhancement effect of chemical enhancers and iontophoresis on the in vitro transdermal and transbuccal delivery of lidocaine HCl (LHCl), nicotine hydrogen tartrate (NHT), and diltiazem HCl (DHCl) using porcine skin and buccal tissues. Dodecyl 2-(N,N-dimethylamino) propionate (DDAIP), dodecyl-2-(N,N-dimethylamino) propionate hydrochloride (DDAIP HCl), N-(4-bromobenzoyl)-S,S-dimethyliminosulfurane (Br-iminosulfurane), and azone (laurocapram) were used as chemical enhancers. The study results showed that the application of iontophoresis at either 0.1 mA or 0.3 mA significantly enhanced transdermal and transmucosal delivery of LHCl, NHT and DHCl. It was also demonstrated that iontophoresis had a more pronounced enhancement effect on transdermal delivery than on transbuccal delivery of LHCl, NHT and DHCl. In addition, DDAIP HCl was found to be the most effective enhancer for transbuccal delivery of LHCl and NHT. Copyright © 2011 Elsevier B.V. All rights reserved.

[Studies on transdermal delivery of ferulic acid through rat skin treated by microneedle arrays].

Science.gov (United States)

Yang, Bing; Du, Shou-ying; Bai, Jie; Shang, Ke-xin; Lu, Yang; Li, Peng-yue

2014-12-01

In order to investigate the characteristics of transdermal delivery of ferulic acid under the treated of microneedle arrays and the influence on permeability of rat skin capillaries, improved Franz-cells were used in the transdermal delivery experiment with the rat skin of abdominal wall and the length of microneedle arrays, different insertion forces, retention time were studied in the influence of characteristics of transdermal delivery of FA. The amount of FA was determined by HPLC system. Intravenous injection Evans blue and FA was added after microneedle arrays treated. Established inflammation model was built by daubing dimethylbenzene. The amount of Evans blue in the rat skin was read at 590 nm wavelength with a Multiskan Go microplate reader. Compared with passive diffusion group the skin pretreated with microneedle arrays had a remarkable enhancement of FA transport (P Microneedle arrays with different length had a remarkable enhancement of FA transport, but was not related to the increase of the length. The research of FA on the reduce of permeability of rat skin capillaries indicated that the skin pretreated with microneedle arrays could reduce the content of Evans blue in the skins of rat significantly compared with the untreated group. The permeation rate of ferulic acid transdermal delivery had remarkable increase under the treated of microneedle arrays and the length of microneedle arrays ,the retention time so as to the insertion force were important to the transdermal delivery of ferulic acid.

Avanafil Liposomes as Transdermal Drug Delivery for Erectile ...

African Journals Online (AJOL)

Avanafil is slightly soluble in ethanol, practically insoluble in water ... transdermal permeability and bioavailability for the treatment of .... Table 1 shows that the EE had higher values for the MLVs .... reason is the lower solubility of avanafil at pH.

[{sup 11}C]diclofenac sodium: synthesis and PET assessment of transdermal penetration

Energy Technology Data Exchange (ETDEWEB)

Petroni, Debora, E-mail: debora.petroni@ifc.cnr.i [CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy); Menichetti, Luca; Sorace, Oreste; Poli, Michela [CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy); Vanasia, Massimo [Gienne Pharma, Via Lorenteggio 270/A, 20152 Milan (Italy); Salvadori, Piero A. [CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy)

2011-02-15

The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) imaging as a new tool to detect transdermal penetration of topical drugs in human subjects. The compound used in the study is sodium 2-[(2,6-dichlorophenyl)amino]phenyl]acetate, better known as diclofenac sodium. This molecule belongs to the family of non-steroidal anti-inflammatory drugs and is considered one of the first choices among non-steroidal anti-inflammatory drugs for the treatment of inflammatory diseases; it is widely used and commercially present in a large number of pharmaceutical forms and formulations. {sup 11}C-labeled diclofenac has been synthesized and coformulated, as an internal indicator, with a proprietary preparation based on the use of a sprayer. The radiolabeled preparation was topically administered to healthy volunteers, and PET imaging was used to evaluate transdermal penetration. Results obtained have demonstrated the efficacy of PET and radiolabeled tracers for the evaluation of transdermal penetration of active pharmaceutical ingredients as topical formulations.

Nanoparticle enabled transdermal drug delivery systems for enhanced dose control and tissue targeting

Science.gov (United States)

Palmer, Brian C.; DeLouise, Lisa A.

2017-01-01

Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. PMID:27983701

Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting.

Science.gov (United States)

Palmer, Brian C; DeLouise, Lisa A

2016-12-15

Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

Evaluation of mesotherapy as a transdermal drug delivery tool.

Science.gov (United States)

Kim, S; Kye, J; Lee, M; Park, B

2016-05-01

There has been no research about the exact mechanism of transdermal drug delivery during mesotherapy. We aimed to evaluate whether the commercial mesogun can be an appropriate technique for a transdermal drug delivery. We injected blue ink into the polyurethane foam or pig skin with three types of mesotherapy using a commercial mesogun, or local made intradermal injector, or a manual injection of syringe. To assess the internal pressure of the cylinder and drug delivery time, we designed the evaluation setup using a needle tip pressure transducer. All types of injectors induced adequate penetration of blue ink into the polyurethane foam without backflow. In the pig skin, blue ink leaked out rapidly with the backward movement of the needle in the commercial mesogun in contrast to the local made injector or the manual injection of syringe. When the time for backward movement of the syringe approaches 1000 ms, the cylinder pressure of the syringe is saturated at around 25 mmHg which can be translated into the dermal pressure of the pig skin. There should be sufficient time between the insertion and withdrawal of the needle of injector for the adequate transdermal drug delivery and it must be considered for mesotherapy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Microneedles for Transdermal Biosensing: Current Picture and Future Direction.

Science.gov (United States)

Ventrelli, Letizia; Marsilio Strambini, Lucanos; Barillaro, Giuseppe

2015-12-09

A novel trend is rapidly emerging in the use of microneedles, which are a miniaturized replica of hypodermic needles with length-scales of hundreds of micrometers, aimed at the transdermal biosensing of analytes of clinical interest, e.g., glucose, biomarkers, and others. Transdermal biosensing via microneedles offers remarkable opportunities for moving biosensing technologies and biochips from research laboratories to real-field applications, and envisages easy-to-use point-of-care microdevices with pain-free, minimally invasive, and minimal-training features that are very attractive for both developed and emerging countries. In addition to this, microneedles for transdermal biosensing offer a unique possibility for the development of biochips provided with end-effectors for their interaction with the biological system under investigation. Direct and efficient collection of the biological sample to be analyzed will then become feasible in situ at the same length-scale of the other biochip components by minimally trained personnel and in a minimally invasive fashion. This would eliminate the need for blood extraction using hypodermic needles and reduce, in turn, related problems, such as patient infections, sample contaminations, analysis artifacts, etc. The aim here is to provide a thorough and critical analysis of state-of-the-art developments in this novel research trend, and to bridge the gap between microneedles and biosensors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transdermal drug delivery: approaches and significance

OpenAIRE

Murthy, SATHYANARAYANA

2012-01-01

S Narasimha MurthyDepartment of Pharmaceutics, The University of Mississippi, USATransdermal drug delivery systems deliver drugs through the skin as an alternative to oral, intravascular, subcutaneous, and transmucosal routes. Potential advantages of transdermal delivery include, but are not limited to, elimination of first-pass metabolism, steady delivery/blood levels, better patient compliance, reduced systemic drug interactions, possible dose intervention, avoidance of medically assisted d...

Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery.

Science.gov (United States)

Bahadoran, Azadeh; Moeini, Hassan; Bejo, Mohd Hair; Hussein, Mohd Zobir; Omar, Abdul Rahman

In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed. First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry. TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-).  In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine.  The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (Pdendrimer is a promising non-viral vector for transdermal use.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Transdermal delivery and cutaneous targeting of antivirals using a penetration enhancer and lysolipid prodrugs.

Science.gov (United States)

Diblíková, Denisa; Kopečná, Monika; Školová, Barbora; Krečmerová, Marcela; Roh, Jaroslav; Hrabálek, Alexandr; Vávrová, Kateřina

2014-04-01

In this work, we investigate prodrug and enhancer approaches for transdermal and topical delivery of antiviral drugs belonging to the 2,6-diaminopurine acyclic nucleoside phosphonate (ANP) group. Our question was whether we can differentiate between transdermal and topical delivery, i.e., to control the delivery of a given drug towards either systemic absorption or retention in the skin. The in vitro transdermal delivery and skin concentrations of seven antivirals, including (R)- and (S)-9-[2-(phosphonomethoxy)propyl]-2,6-diaminopurine (PMPDAP), (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine ((S)-HPMPDAP), its 8-aza analog, and their cyclic and hexadecyloxypropyl (HDP) prodrugs, was investigated with and without the penetration enhancer dodecyl-6-(dimethylamino)hexanoate (DDAK) using human skin. The ability of ANPs to cross the human skin barrier was very low (0.5-1.4 nmol/cm(2)/h), and the majority of the compounds were found in the stratum corneum, the uppermost skin layer. The combination of antivirals and the penetration enhancer DDAK proved to be a viable approach for transdermal delivery, especially in case of (R)-PMPDAP, an anti-HIV effective drug (30.2 ± 2.3 nmol/cm(2)/h). On the other hand, lysophospholipid-like HDP prodrugs, e.g., HDP-(S)-HPMPDAP, reached high concentrations in viable epidermis without significant systemic absorption. By using penetration enhancers or lysolipid prodrugs, it is possible to effectively target systemic diseases by the transdermal route or to target cutaneous pathologies by topical delivery.

Contingency management for alcohol use reduction: a pilot study using a transdermal alcohol sensor.

Science.gov (United States)

Barnett, Nancy P; Tidey, Jennifer; Murphy, James G; Swift, Robert; Colby, Suzanne M

2011-11-01

Contingency management (CM) has not been thoroughly evaluated as a treatment for alcohol abuse or dependence, in part because verification of alcohol use reduction requires frequent in-person breath tests. Transdermal alcohol sensors detect alcohol regularly throughout the day, providing remote monitoring and allowing for rapid reinforcement of reductions in use. The purpose of this study was to evaluate the efficacy of CM for reduction in alcohol use, using a transdermal alcohol sensor to provide a continuous measure of alcohol use. Participants were 13 heavy drinking adults who wore the Secure Continuous Remote Alcohol Monitoring (SCRAM) bracelet for three weeks and provided reports of alcohol and drug use using daily web-based surveys. In Week 1, participants were asked to drink as usual; in Weeks 2 and 3, they were reinforced on an escalating schedule with values ranging from $5 to $17 per day on days when alcohol use was not reported or detected by the SCRAM. Self-reports of percent days abstinent and drinks per week, and transdermal measures of average and peak transdermal alcohol concentration and area under the curve declined significantly in Weeks 2-3. A nonsignificant but large effect size for reduction in days of tobacco use also was found. An adjustment to the SCRAM criteria for detecting alcohol use provided an accurate but less conservative method for use with non-mandated clients. Results support the efficacy of CM for alcohol use reductions and the feasibility of using transdermal monitoring of alcohol use for clinical purposes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Contingency Management for Alcohol Use Reduction: A Pilot Study using a Transdermal Alcohol Sensor*

Science.gov (United States)

Barnett, Nancy P.; Tidey, Jennifer; Murphy, James G.; Swift, Robert; Colby, Suzanne M.

2011-01-01

Background Contingency management (CM) has not been thoroughly evaluated as a treatment for alcohol abuse or dependence, in part because verification of alcohol use reduction requires frequent in-person breath tests. Transdermal alcohol sensors detect alcohol regularly throughout the day, providing remote monitoring and allowing for rapid reinforcement of reductions in use. Methods The purpose of this study was to evaluate the efficacy of CM for reduction in alcohol use, using a transdermal alcohol sensor to provide a continuous measure of alcohol use. Participants were 13 heavy drinking adults who wore the Secure Continuous Remote Alcohol Monitoring (SCRAM) bracelet for three weeks and provided reports of alcohol and drug use using daily web-based surveys. In Week 1, participants were asked to drink as usual; in Weeks 2 and 3, they were reinforced on an escalating schedule with values ranging from $5-$17 per day on days when alcohol use was not reported or detected by the SCRAM. Results Self-reports of percent days abstinent and drinks per week, and transdermal measures of average and peak transdermal alcohol concentration and area under the curve declined significantly in Weeks 2-3. A nonsignificant but large effect size for reduction in days of tobacco use also was found. An adjustment to the SCRAM criteria for detecting alcohol use provided an accurate but less conservative method for use with non-mandated clients. Conclusion Results support the efficacy of CM for alcohol use reductions and the feasibility of using transdermal monitoring of alcohol use for clinical purposes. PMID:21665385

Current and emerging lipid-based systems for transdermal drug delivery.

Science.gov (United States)

Singla, Sumeet K; Sachdeva, Vishal

2015-01-01

Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

Ultrasound-mediated microbubble enhancement of radiation therapy studied using three-dimensional high-frequency power Doppler ultrasound.

Science.gov (United States)

Kwok, Sheldon J J; El Kaffas, Ahmed; Lai, Priscilla; Al Mahrouki, Azza; Lee, Justin; Iradji, Sara; Tran, William Tyler; Giles, Anoja; Czarnota, Gregory J

2013-11-01

Tumor responses to high-dose (>8 Gy) radiation therapy are tightly connected to endothelial cell death. In the study described here, we investigated whether ultrasound-activated microbubbles can locally enhance tumor response to radiation treatments of 2 and 8 Gy by mechanically perturbing the endothelial lining of tumors. We evaluated vascular changes resulting from combined microbubble and radiation treatments using high-frequency 3-D power Doppler ultrasound in a breast cancer xenograft model. We compared treatment effects and monitored vasculature damage 3 hours, 24 hours and 7 days after treatment delivery. Mice treated with 2 Gy radiation and ultrasound-activated microbubbles exhibited a decrease in vascular index to 48 ± 10% at 24 hours, whereas vascular indices of mice treated with 2 Gy radiation alone or microbubbles alone were relatively unchanged at 95 ± 14% and 78 ± 14%, respectively. These results suggest that ultrasound-activated microbubbles enhance the effects of 2 Gy radiation through a synergistic mechanism, resulting in alterations of tumor blood flow. This novel therapy may potentiate lower radiation doses to preferentially target endothelial cells, thus reducing effects on neighboring normal tissue and increasing the efficacy of cancer treatments. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway: an overview

OpenAIRE

Naves, Lucas; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Soares, Gra?a

2017-01-01

In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and ...

Electron beam processed transdermal delivery system for administration of an anti-anginal agent

Science.gov (United States)

Kotiyan, P. N.; Vavia, P. R.; Bharadwaj, Y. K.; Sabarwal, S.; Majali, A. B.

2002-12-01

Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak ®1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed.

Electron beam processed transdermal delivery system for administration of an anti-anginal agent

Energy Technology Data Exchange (ETDEWEB)

Kotiyan, P.N. E-mail: pramila-kotiyan@uiowa.edu; Vavia, P.R.; Bharadwaj, Y.K.; Sabarwal, S.; Majali, A.B

2002-12-01

Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak[reg]1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed.

Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting

Directory of Open Access Journals (Sweden)

Brian C. Palmer

2016-12-01

Full Text Available Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

Electron beam processed transdermal delivery system for administration of an anti-anginal agent

International Nuclear Information System (INIS)

Kotiyan, P.N.; Vavia, P.R.; Bharadwaj, Y.K.; Sabarwal, S.; Majali, A.B.

2002-01-01

Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak[reg]1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed

Hyaluronan-Based Nanohydrogels as Effective Carriers for Transdermal Delivery of Lipophilic Agents: Towards Transdermal Drug Administration in Neurological Disorders

Directory of Open Access Journals (Sweden)

Seong Uk Son

2017-12-01

Full Text Available We suggest a convenient nanoemulsion fabrication method to create hyaluronan (HA-based nanohydrogels for effective transdermal delivery. First, hyaluronan-conjugated dodecylamine (HA–Do HA-based polymers to load the lipophilic agents were synthesized with hyaluronan (HA and dodecylamine (Do by varying the substitution ratio of Do to HA. The synthetic yield of HA–Do was more than 80% (HA–Do (A: 82.7 ± 4.7%, HA–Do (B: 87.1 ± 3.9% and HA–Do (C: 81.4 ± 4.5%. Subsequently, nanohydrogels were fabricated using the nanoemulsion method. Indocyanine green (ICG simultaneously self-assembled with HA–Do, and the size depended on the substitution ratio of Do in HA–Do (nanohydrogel (A: 118.0 ± 2.2 nm, nanohydrogel (B: 121.9 ± 11.4 nm, and nanohydrogel (C: 142.2 ± 3.8 nm. The nanohydrogels were delivered into cells, and had excellent biocompatibility. Especially, nanohydrogel (A could deliver and permeate ICG into the deep skin layer, the dermis. This suggests that nanohydrogels can be potent transdermal delivery systems.

Inkjet printing of insulin microneedles for transdermal delivery.

Science.gov (United States)

Ross, Steven; Scoutaris, Nicolaos; Lamprou, Dimitrios; Mallinson, David; Douroumis, Dennis

2015-08-01

Inkjet printing technology was used to apply insulin polymeric layers on metal microneedles for transdermal delivery. A range of various polymers such as gelatin (GLN), polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol (SOL), poly(2-ethyl-2-oxazoline) (POX) and trehalose (THL) were assessed for their capacity to form thin uniform and homogeneous layers that preserve insulin intact. Atomic force microscopy (AFM) showed homogeneous insulin-polymer layers without any phase separation while SOL demonstrated the best performance. Circular discroism (CD) analysis of rehydrated films showed that insulin's alpha helices and β-sheet were well preserved for THL and SOL. In contrast, GLN and POX insulin layers revealed small band shifts indicating possible conformational changes. Insulin release in Franz diffusion cells from MNs inserted into porcine skin showed rapid release rates for POX and GLN within the first 20 min. Inkjet printing was proved an effective approach for transdermal delivery of insulin in solid state.

Fabrication, appraisal, and transdermal permeation of sildenafil citrate-loaded nanostructured lipid carriers versus solid lipid nanoparticles

Science.gov (United States)

Elnaggar, Yosra SR; El-Massik, Magda A; Abdallah, Ossama Y

2011-01-01

Although sildenafil citrate (SC) is used extensively for erectile dysfunction, oral delivery of SC encounters many obstacles. Furthermore, the physicochemical characteristics of this amphoteric drug are challenging for delivery system formulation and transdermal permeation. This article concerns the assessment of the potential of nanomedicine for improving SC delivery and transdermal permeation. SC-loaded nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) were fabricated using a modified high-shear homogenization technique. Nanoparticle optimization steps included particle size analysis, entrapment efficiency (EE) determination, freeze-drying and reconstitution, differential scanning calorimetry, in vitro release, stability study and high-performance liquid chromatography analysis. Transdermal permeation of the nanocarriers compared with SC suspension across human skin was assessed using a modified Franz diffusion cell assembly. Results revealed that SLNs and NLCs could be optimized in the nanometric range (180 and 100 nm, respectively) with excellent EE (96.7% and 97.5%, respectively). Nanoparticles have significantly enhanced in vitro release and transdermal permeation of SC compared with its suspensions. Furthermore, transdermal permeation of SC exhibited higher initial release from both SLN and NLC formulations followed by controlled release, with promising implications for faster onset and longer drug duration. Nanomedicines prepared exhibited excellent physical stability for the study period. Solid nanoparticles optimized in this study successfully improved SC characteristics, paving the way for an efficient topical Viagra® product. PMID:22238508

Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine

Science.gov (United States)

Hong, Xiaoyun; Wei, Liangming; Wu, Fei; Wu, Zaozhan; Chen, Lizhu; Liu, Zhenguo; Yuan, Weien

2013-01-01

Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. PMID:24039404

Enhancement of transdermal delivery of ibuprofen using microemulsion vehicle.

Science.gov (United States)

Hu, Liandong; Hu, Qiaofeng; Yang, Jianxue

2014-10-01

The objective of this study was to find a stable microemulsion vehicle for transdermal delivery of ibuprofen to improve the skin permeability. Microemulsion was prepared using different sorts of oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were used to evaluate the microemulsion domain. The effects of oleic acid and surfactant mixture on skin permeation of ibuprofen were evaluated with excised skins. The optimum formulation F3 consisting of 6% oleic acid, 30% Cremophor RH40/Transcutol P (2:1, w/w) and 59% water phase, showed a high permeation rate of 42.98 µg/cm(2)/hr. The mean droplet size of microemulsion was about 43 nm and no skin irritation signs were observed on the skin of rabbits. These results indicated that this novel microemulsion is a useful formulation for the transdermal delivery of ibuprofen.

Dynamic Behavior of Microbubbles during Long Ultrasound Tone-Burst Excitation: Mechanistic Insights into Ultrasound-Microbubble Mediated Therapeutics Using High-Speed Imaging and Cavitation Detection.

Science.gov (United States)

Chen, Xucai; Wang, Jianjun; Pacella, John J; Villanueva, Flordeliza S

2016-02-01

Ultrasound (US)-microbubble (MB)-mediated therapies have been found to restore perfusion and enhance drug/gene delivery. On the presumption that MBs do not persist during long US exposure under high acoustic pressures, most schemes use short US pulses when a high US pressure is employed. However, we recently observed an enhanced thrombolytic effect using long US pulses at high acoustic pressures. Therefore, we explored the fate of MBs during long tone-burst exposures (5 ms) at various acoustic pressures and MB concentrations via direct high-speed optical observation and passive cavitation detection. MBs first underwent stable or inertial cavitation depending on the acoustic pressure and then formed gas-filled clusters that continued to oscillate, break up and form new clusters. Cavitation detection confirmed continued, albeit diminishing, acoustic activity throughout the 5-ms US excitation. These data suggest that persisting cavitation activity during long tone bursts may confer additional therapeutic effects. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Nonaqueous gel for the transdermal delivery of a DTPA penta-ethyl ester prodrug.

Science.gov (United States)

Zhang, Yong; Sadgrove, Matthew P; Sueda, Katsuhiko; Yang, Yu-Tsai; Pacyniak, Erik K; Kagel, John R; Braun, Brenda A; Zamboni, William C; Mumper, Russell J; Jay, Michael

2013-04-01

Diethylenetriamine pentaacetic acid penta-ethyl ester, designated as C2E5, was successfully incorporated into a nonaqueous gel for transdermal delivery. The thermal and rheological properties of a formulation containing 40% C2E5, 20% ethyl cellulose, and 40% Miglyol 840® prepared using the solvent evaporation method demonstrated that the gel had acceptable content uniformity and flow properties. In vitro studies showed that C2E5 was steadily released from the gel at a rate suitable for transdermal delivery. Topical application of the gel at a 200 mg C2E5/kg dose level in rats achieved significantly higher plasma exposures of several active metabolites compared with neat C2E5 oil at the same dose level. The results suggest that transdermal delivery of a chelator prodrug is an effective radionuclide decorporation strategy by delivering chelators to the circulation with a pharmacokinetic profile that is more consistent with the biokinetic profile of transuranic elements in contaminated individuals.

Transdermal and intradermal delivery of therapeutic agents: application of physical technologies

National Research Council Canada - National Science Library

Banga, Ajay K

2011-01-01

.... Commercialization of transdermal drug delivery requires technology from many disciplines beyond pharmaceutical sciences, such as polymer chemistry, adhesion sciences, mass transport, web film coating...

Microdose transdermal estrogen therapy for relief of vulvovaginal symptoms in postmenopausal women.

Science.gov (United States)

Bachmann, Gloria A; Schaefers, Matthias; Uddin, Alkaz; Utian, Wulf H

2009-01-01

The aim of this study was to investigate the effectiveness of microdose transdermal 17beta-estradiol (E2) therapy in postmenopausal women with moderate to severe vulvovaginal symptoms. This report is based on a subset of 121 women who reported most bothersome moderate or severe vulvovaginal symptoms at baseline, from a previous randomized, double-blind, placebo-controlled, multicenter study of 425 healthy, symptomatic, postmenopausal women. Recruits had experienced at least 7 moderate or severe hot flushes daily for at least 1 week or at least 50 moderate or severe hot flushes per week for at least 1 week. Effects on coprimary efficacy variables have been reported previously. Participants received low-dose transdermal E2 plus levonorgestrel (n = 43; nominal delivery 0.023 mg/d E2/0.0075 mg/d levonorgestrel), microdose E2 (n = 42; nominal delivery 0.014 mg/d), or placebo (n = 36) for 12 weeks. Secondary efficacy variables reported herein include mean change from baseline in vaginal pH and vaginal maturation index, the proportion of women with symptoms of vulvar and vaginal atrophy at baseline and week 12, and the proportion of women with moderate-to-severe symptoms of vulvar and vaginal atrophy. Microdose transdermal E2 treatment was associated with a consistent benefit versus placebo in women with vulvovaginal atrophy. There was a statistically significant difference between both E2 versus placebo for changes in vaginal pH and vaginal maturation index. Microdose transdermal E2 offers a useful addition to the therapeutic armamentarium for postmenopausal women in whom vulvovaginal symptoms are particularly troublesome.

Efficacy and transdermal absorption of permethrin in scabies patients

NARCIS (Netherlands)

van der Rhee, H.J.; Farquhar, J A; Vermeulen, N P

1989-01-01

The clinical efficacy and transdermal absorption of permethrin, a new synthetic insecticide was investigated in ten scabies patients. All patients were successfully treated with one application of a cream, containing 5% permethrin. Apart from mild postscabies dermatitis no side-effects were

Tanscranial Threshold of Inertial Cavitation Induced by Diagnosticc Ultrasound and Microbubbles

NARCIS (Netherlands)

Liu, J.; Gao, S.; Porter, T.R.; Everbach, C; Shi, W.; Vignon, F.; Powers, J.; Lof, J.; Turner, J.; Xie, F.

2011-01-01

Background: Inertial cavitation may cause hazardous bioeffects whileusing ultrasound and microbubble mediated thrombolysis. The purposeof this study was to investigate the influence of ultrasound pulselength and temporal bone on inertial cavitation thresholds within the brain utilizing transtemporal

Design and Development of a Proniosomal Transdermal Drug ...

African Journals Online (AJOL)

Purpose: The aim of the study was to develop a proniosomal carrier system for captopril for the treatment of hypertension that is capable of efficiently delivering entrapped drug over an extended period of time. Method: The potential of proniosomes as a transdermal drug delivery system for captopril was investigated by ...

Anti-inflammatory effect with high intensity focused ultrasound-mediated pulsatile delivery of diclofenac.

Science.gov (United States)

Wang, Chih-Yu; Yang, Chih-Hui; Lin, Yung-Sheng; Chen, Chih-Hsin; Huang, Keng-Shiang

2012-02-01

A pulsatile ultrasound controlled drug release platform with diclofenac-loaded alginate microcapsules (fabricated with a home-made electrostatic device, 75% embedded rate) was established to evaluate anti-inflammation efficiency. Better anti-inflammation efficiency was found using the ultrasound system and the drug delivery can be adjusted based on the programmed ultrasound cycle. The results of the in vitro study show that an approx. 30% higher drug release rate was obtained by using continuous ultrasound irradiation (9-Watt, 180 min), and an approx. 16% higher drug release rate was obtained by using pulsatile ultrasound irradiation (9-Watt, 60 min) compared to without ultrasound activation. For the in vivo study, the anti-inflammatory test with carrageenan-induced rat's paw edema shows that diclofenac-loaded microcapsules followed by ultrasound irradiation (9-Watt, 60 min) contributed to an 81% inhibition rate, which was significantly higher than diclofenac only (approx. 60% higher). In addition, because of their heat conducting properties, gold nanoparticles encapsulated in the diclofenac-loaded microcapsules resulted in better drug release efficiency, but tended to depress the anti-inflammation effect. Copyright © 2011 Elsevier Ltd. All rights reserved.

Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats.

Science.gov (United States)

Delamaide Gasper, Joy A; Barnes Heller, Heidi L; Robertson, Michelle; Trepanier, Lauren A

2015-04-01

Seizures are a common cause of neurologic disease, and phenobarbital (PB) is the most commonly used antiepileptic drug. Chronic oral dosing can be challenging for cat owners, leading to poor compliance. The purpose of this study was to determine if the transdermal administration of PB could achieve serum PB concentrations of between 15 and 45 μg/ml in healthy cats. Nineteen healthy cats were enrolled in three groups. Transdermal PB in pluronic lecithin organogel (PLO) was applied to the pinnae for 14 days at a dosage of 3 mg/kg q12h in group 1 (n = 6 cats) and 9 mg/kg q12h in group 2 (n = 7 cats). Transdermal PB in Lipoderm Activemax was similarly applied at 9 mg/kg q12h for 14 days in group 3 (n = 6 cats). Steady-state serum PB concentrations were measured at trough, and at 2, 4 and 6 h after the morning dose on day 15. In group 1, median concentrations ranged from 6.0-7.5 μg/ml throughout the day (observed range 0-11 μg/ml). Group 2 median concentrations were 26.0 μg/ml (observed range 18.0-37.0 μg/ml). For group 3, median concentrations ranged from 15.0-17.0 μg/ml throughout the day (range 5-29 μg/ml). Side effects were mild. One cat was withdrawn from group 2 owing to ataxia and sedation. These results show therapeutic serum PB concentrations can be achieved in cats following chronic transdermal administration of PB in PLO at a dosage of 9 mg/kg q12h. More individual variation was noted using Lipoderm Activemax. Transdermal administration may be an alternative for cats that are difficult to medicate orally. © ISFM and AAFP 2014.

Novel engineered systems for oral, mucosal and transdermal drug delivery.

Science.gov (United States)

Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng

2013-08-01

Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

Current advances in transdermal delivery of drugs for Alzheimer's disease

Science.gov (United States)

Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

2017-01-01

Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients. PMID:28706327

Current advances in transdermal delivery of drugs for Alzheimer's disease.

Science.gov (United States)

Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

2017-01-01

Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients.

Exposure to Fentanyl After Transdermal Patch Administration for Cancer Pain Management.

Science.gov (United States)

Bista, Sudeep R; Haywood, Alison; Hardy, Janet; Norris, Ross; Hennig, Stefanie

2016-06-01

This study aimed to describe exposure after fentanyl transdermal patch administration in patients with advanced cancer to quantify variability around the exposure. Patients (n  =  56) with advanced cancer who received transdermal fentanyl (Durogesic®; median dose, 50 μg/h; range, 12-200 μg/h) provided venous blood samples (n  =  163) at various times (0.5-72 hours) during several patch application intervals. Plasma fentanyl concentration was determined (median, 0.9 μg/L; range, 0.04-9.7 μg/L) by high-performance liquid chromatography coupled to tandem mass spectrometry. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling with NONMEM. A 1-compartment distribution model with first-order absorption and elimination described fentanyl exposure after transdermal patch administration. Fentanyl apparent clearance (between-subject variability [BSV], %) was estimated at 122 L/h/70 kg and 38.5%, respectively. The absorption rate constant was 0.013 h(-1) . Between-occasion variability on apparent clearance was 22.0%, which was lower than BSV, suggesting predictable exposure within the same patient and justifying therapeutic drug monitoring. Except for weight-based dosing, no other patient characteristic could be identified to guide initial fentanyl dose selection in patients with advanced cancer. © 2015, The American College of Clinical Pharmacology.

Transdermal thiol-acrylate polyethylene glycol hydrogel synthesis using near infrared light

Science.gov (United States)

Chung, Solchan; Lee, Hwangjae; Kim, Hyung-Seok; Kim, Min-Gon; Lee, Luke P.; Lee, Jae Young

2016-07-01

Light-induced polymerization has been widely applied for hydrogel synthesis, which conventionally involves the use of ultraviolet or visible light to activate a photoinitiator for polymerization. However, with these light sources, transdermal gelation is not efficient and feasible due to their substantial interactions with biological systems, and thus a high power is required. In this study, we used biocompatible and tissue-penetrating near infrared (NIR) light to remotely trigger a thiol-acrylate reaction for efficient in vivo gelation with good controllability. Our gelation system includes gold nanorods as a photothermal agent, a thermal initiator, diacrylate polyethylene glycol (PEG), and thiolated PEG. Irradiation with a low-power NIR laser (0.3 W cm-2) could induce gelation via a mixed-mode reaction with a small increase in temperature (~5 °C) under the optimized conditions. We also achieved successful transdermal gelation via the NIR-assisted photothermal thiol-acryl reactions. This new type of NIR-assisted thiol-acrylate polymerization provides new opportunities for in situ hydrogel formation for injectable hydrogels and delivery of drugs/cells for various biomedical applications.Light-induced polymerization has been widely applied for hydrogel synthesis, which conventionally involves the use of ultraviolet or visible light to activate a photoinitiator for polymerization. However, with these light sources, transdermal gelation is not efficient and feasible due to their substantial interactions with biological systems, and thus a high power is required. In this study, we used biocompatible and tissue-penetrating near infrared (NIR) light to remotely trigger a thiol-acrylate reaction for efficient in vivo gelation with good controllability. Our gelation system includes gold nanorods as a photothermal agent, a thermal initiator, diacrylate polyethylene glycol (PEG), and thiolated PEG. Irradiation with a low-power NIR laser (0.3 W cm-2) could induce gelation

Advanced progress of microencapsulation technologies: in vivo and in vitro models for studying oral and transdermal drug deliveries.

Science.gov (United States)

Lam, P L; Gambari, R

2014-03-28

This review provides an overall discussion of microencapsulation systems for both oral and transdermal drug deliveries. Clinically, many drugs, especially proteins and peptides, are susceptible to the gastrointestinal tract and the first-pass metabolism after oral administration while some drugs exhibit low skin permeability through transdermal delivery route. Medicated microcapsules as oral and transdermal drug delivery vehicles are believed to offer an extended drug effect at a relatively low dose and provide a better patient compliance. The polymeric microcapsules can be produced by different microencapsulation methods and the drug microencapsulation technology provides the quality preservation for drug stabilization. The release of the entrapped drug is controlled and prolonged for specific usages. Some recent studies have focused on the evaluation of drug containing microcapsules on potential biological and therapeutic applications. For the oral delivery, in vivo animal models were used for evaluating possible treatment effects of drug containing microcapsules. For the transdermal drug delivery, skin delivery models were introduced to investigate the potential skin delivery of medicated microcapsules. Finally, the challenges and limitations of drug microencapsulation in real life are discussed and the commercially available drug formulations using microencapsulation technology for oral and transdermal applications are shown. Copyright © 2014 Elsevier B.V. All rights reserved.

Carbon Nanotube Membranes for use in the Transdermal Treatment of Nicotine Addiction and Opioid Withdrawal Symptoms

Directory of Open Access Journals (Sweden)

Caroline L. Strasinger

2009-01-01

Full Text Available Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual's needs will increase patient compliance as well as provide much more efficient therapy. The purpose of this paper is to discuss the applicability of using carbon nanotube membranes in transdermal systems for treatment of drug abuse.

Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application

Directory of Open Access Journals (Sweden)

Mahmood S

2014-09-01

Full Text Available Syed Mahmood, Muhammad Taher, Uttam Kumar Mandal Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia (IIUM, Pahang Darul Makmur, Malaysia Abstract: Raloxifene hydrochloride, a highly effective drug for the treatment of invasive breast cancer and osteoporosis in post-menopausal women, shows poor oral bioavailability of 2%. The aim of this study was to develop, statistically optimize, and characterize raloxifene hydrochloride-loaded transfersomes for transdermal delivery, in order to overcome the poor bioavailability issue with the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental design. Phospholipon® 90G, sodium deoxycholate, and sonication time, each at three levels, were selected as independent variables, while entrapment efficiency, vesicle size, and transdermal flux were identified as dependent variables. The formulation was characterized by surface morphology and shape, particle size, and zeta potential. Ex vivo transdermal flux was determined using a Hanson diffusion cell assembly, with rat skin as a barrier medium. Transfersomes from the optimized formulation were found to have spherical, unilamellar structures, with a ­homogeneous distribution and low polydispersity index (0.08. They had a particle size of 134±9 nM, with an entrapment efficiency of 91.00%±4.90%, and transdermal flux of 6.5±1.1 µg/cm2/hour. Raloxifene hydrochloride-loaded transfersomes proved significantly superior in terms of amount of drug permeated and deposited in the skin, with enhancement ratios of 6.25±1.50 and 9.25±2.40, respectively, when compared with drug-loaded conventional liposomes, and an ethanolic phosphate buffer saline. Differential scanning calorimetry study revealed a greater change in skin structure, compared with a control sample, during the ex vivo drug diffusion study. Further, confocal laser

Galactosyl Pentadecene Reversibly Enhances Transdermal and Topical Drug Delivery

Czech Academy of Sciences Publication Activity Database

Kopečná, M.; Macháček, M.; Prchalová, Eva; Štěpánek, P.; Drašar, P.; Kotora, Martin; Vávrová, K.

2017-01-01

Roč. 34, č. 10 (2017), s. 2097-2108 ISSN 0724-8741 Institutional support: RVO:61388963 Keywords : galactoside * penetration enhancers * sugar * topical drug delivery * transdermal drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Pharmacology and pharmacy Impact factor: 3.002, year: 2016

Optimization of Microemulsion Based Transdermal Gel of Triamcinolone.

Science.gov (United States)

Jagdale, Swati; Chaudhari, Bhagyashree

2017-01-01

Triamcinolone is a long acting corticosteroid used in the treatment of arthritis, eczema, psoriasis and similar conditions which cause inflammation. Triamcinolone has half-life of 88min. Prolonged oral use is associated with gastrointestinal adverse effects as peptic ulcer, abdominal distention and ulcerative esophagitis as described in various patents. Microemulgel offers advantage of better stability, better loading capacity and controlled release especially for drug with short half life. Objective of the present study was to optimize microemulgel based transdermal delivery of triamcinolone. Saturated solubility of triamcinolone in various oils, surfactants and co-surfactants is estimated. Pseudo-ternary phase diagrams were constructed to determine the region of transparent microemulsion. Microemulsion was evaluated for globule size (FE-SEM, zetasizer), % transmittance, pH, viscosity, conductivity etc. Design of experiment was used to optimize microemulsion based gel. Carbopol 971P and HPMC K100M were used as independent variables. Microemulsion based gel was evaluated for in-vitro as well as ex-vivo parameters. Microemulsion was formulated with oleic acid, lauroglycol FCC and propylene glycol. PDI 0.197 indicated microemulsion is mono-disperse. 32 factorial design gave batch F8 as optimized. Design expert suggested drug release; gel viscosity and bio-adhesive strength were three significant dependant factors affecting the transdermal delivery. F8 showed drug release 92.62.16±1.22% through egg membrane, 95.23±1.44% through goat skin after 8hr and Korsmeyer-Peppas release model was followed. It can be concluded that a stable, effective controlled release transdermal microemulgel was optimised for triamcinolone. This would be a promising tool to deliver triamcinolone with enhanced bioavailability and reduced dosing frequency. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

In vitro evaluation of transdermal nicotine delivery systems commercially available in Brazil

Directory of Open Access Journals (Sweden)

André Luís Morais Ruela

2013-09-01

Full Text Available The aim of this study was to develop and validate a method for evaluating the release and skin permeation from transdermal nicotine patches using the vertical diffusion cell (VDC. The VDC is an experimental apparatus employed in research, development, and the pharmaceutical field because it can simulate conditions closest to those established in clinical trials. Two transdermal nicotine delivery systems marketed in Brazil to release 14 mg over 24 hours were evaluated. Release studies were carried out using a regenerated cellulose dialysis membrane and permeation studies were carried out using excised porcine ear skin. The results indicated that nicotine release from both evaluated patches follows Higuchi's release kinetics, while skin permeation studies indicated zero-order release kinetics. Nicotine release rates were different between both evaluated patches, but drug permeation rates were not significantly different. According to validation studies, the method was appropriate for evaluating in vitro performance of nicotine patches. The proposed method can be applied to in vitro comparative studies between different commercial nicotine patches and may be used as an auxiliary tool in the design of new transdermal nicotine delivery systems.

Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging.

Science.gov (United States)

Theek, Benjamin; Gremse, Felix; Kunjachan, Sijumon; Fokong, Stanley; Pola, Robert; Pechar, Michal; Deckers, Roel; Storm, Gert; Ehling, Josef; Kiessling, Fabian; Lammers, Twan

2014-05-28

The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomography-fluorescence molecular tomography (CT-FMT), the tumor accumulation of a ~10 nm-sized near-infrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice. In the same set of animals, two different ceUS techniques (2D MIOT and 3D B-mode imaging) were employed to assess tumor vascularization. Subsequently, the degree of tumor vascularization was correlated with the degree of EPR-mediated drug targeting. Depending on the optical imaging protocol used, the tumor accumulation of the polymeric drug carrier ranged from 5 to 12% of the injected dose. The degree of tumor vascularization, determined using ceUS, varied from 4 to 11%. For both hybrid CT-FMT protocols, a good correlation between the degree of tumor vascularization and the degree of tumor accumulation was observed, within the case of reconstructed CT-FMT, correlation coefficients of ~0.8 and p-values of EPR, and potentially also to pre-select patients likely to respond to passively tumor-targeted nanomedicine treatments. Copyright © 2014 Elsevier B.V. All rights reserved.

Quantitative ultrasound characterization of tumor cell death: ultrasound-stimulated microbubbles for radiation enhancement.

Directory of Open Access Journals (Sweden)

Hyunjung Christina Kim

Full Text Available The aim of this study was to assess the efficacy of quantitative ultrasound imaging in characterizing cancer cell death caused by enhanced radiation treatments. This investigation focused on developing this ultrasound modality as an imaging-based non-invasive method that can be used to monitor therapeutic ultrasound and radiation effects. High-frequency (25 MHz ultrasound was used to image tumor responses caused by ultrasound-stimulated microbubbles in combination with radiation. Human prostate xenografts grown in severe combined immunodeficiency (SCID mice were treated using 8, 80, or 1000 µL/kg of microbubbles stimulated with ultrasound at 250, 570, or 750 kPa, and exposed to 0, 2, or 8 Gy of radiation. Tumors were imaged prior to treatment and 24 hours after treatment. Spectral analysis of images acquired from treated tumors revealed overall increases in ultrasound backscatter intensity and the spectral intercept parameter. The increase in backscatter intensity compared to the control ranged from 1.9±1.6 dB for the clinical imaging dose of microbubbles (8 µL/kg, 250 kPa, 2 Gy to 7.0±4.1 dB for the most extreme treatment condition (1000 µL/kg, 750 kPa, 8 Gy. In parallel, in situ end-labelling (ISEL staining, ceramide, and cyclophilin A staining demonstrated increases in cell death due to DNA fragmentation, ceramide-mediated apoptosis, and release of cyclophilin A as a result of cell membrane permeabilization, respectively. Quantitative ultrasound results indicated changes that paralleled increases in cell death observed from histology analyses supporting its use for non-invasive monitoring of cancer treatment outcomes.

Acute Intoxication by Transdermal Opium Application in Infants: Two Case Reports

Directory of Open Access Journals (Sweden)

Iraj Sedighi

2012-05-01

Full Text Available Background: Acute opium intoxication is one of the most common causes of poisoning in children in Iran. Although most cases are accidental, traditional misuse of opium for symptomatic therapy of various childhood diseases also contributes to high rate of opium intoxication in Iran. Cases: Here, we report two cases of opium intoxication in infants resulted from transdermal application of opium on burned skin. To our knowledge this is the first case report of intoxication from transdermal misuse of opium. Conclusion: Health care providers should be aware about signs and symptoms of opium intoxication in children. Opium intoxication should be suspected in each child with history of a recent burn injury that presented with decreased level of consciousness.

The Influence of Solid Microneedles on the Transdermal Delivery of Selected Antiepileptic Drugs

Directory of Open Access Journals (Sweden)

Julia Nguyen

2016-11-01

Full Text Available The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm2/h compared to passive delivery (12.83 ± 6.30 µg/cm2/h. For carbamazepine in 20% ethanol, passive transdermal flux of 7.85 ± 0.60 µg/cm2/h was observed compared to 10.85 ± 0.11 µg/cm2/h after microneedle treatment. Carbamazepine reconstituted in 30% ethanol resulted in only a 1.19-fold increase in drug permeation across porcine skin (36.73 ± 1.83 µg/cm2/h versus 30.74 ± 1.32 µg/cm2/h. Differences in flux values of untreated and microneedle-treated porcine skin using solid microneedles for the transdermal delivery of tiagabine were statistically significant. Although there were 1.38- and 1.19-fold increases in transdermal flux values of carbamazepine when applied as 20% and 30% ethanol solutions across microneedle-treated porcine skin, respectively, the increases were not statistically significant.

Gold nanorods in an oil-base formulation for transdermal treatment of type 1 diabetes in mice

Science.gov (United States)

Nose, Keisuke; Pissuwan, Dakrong; Goto, Masahiro; Katayama, Yoshiki; Niidome, Takuro

2012-05-01

Efficient transdermal insulin delivery to the systemic circulation would bring major benefit to diabetic patients. We investigated the possibility of using gold nanorods (GNRs) that formed a complex with an edible surfactant and insulin (INS) in an oil phase to form a solid-in-oil (SO) formulation (SO-INS-GNR) for transdermal treatment of diabetes. Diabetic mice comprised the model for our study. In vitro, there was high penetration of insulin through the stratum corneum (SC) and the dermis in mouse skin treated with an SO-INS-GNR complex plus near-infrared (NIR) light irradiation. Blood glucose levels in the diabetic mice were significantly decreased after treatment with SO-INS-GNR plus irradiation. To our knowledge, this is the first study to use gold nanorods for systemic insulin delivery through the skin. The use of an SO-INS-GNR complex combined with NIR irradiation may provide the possibility of transdermal insulin delivery to diabetic patients.Efficient transdermal insulin delivery to the systemic circulation would bring major benefit to diabetic patients. We investigated the possibility of using gold nanorods (GNRs) that formed a complex with an edible surfactant and insulin (INS) in an oil phase to form a solid-in-oil (SO) formulation (SO-INS-GNR) for transdermal treatment of diabetes. Diabetic mice comprised the model for our study. In vitro, there was high penetration of insulin through the stratum corneum (SC) and the dermis in mouse skin treated with an SO-INS-GNR complex plus near-infrared (NIR) light irradiation. Blood glucose levels in the diabetic mice were significantly decreased after treatment with SO-INS-GNR plus irradiation. To our knowledge, this is the first study to use gold nanorods for systemic insulin delivery through the skin. The use of an SO-INS-GNR complex combined with NIR irradiation may provide the possibility of transdermal insulin delivery to diabetic patients. Electronic supplementary information (ESI) available. See DOI: 10

Carbon Nanotube Membranes for use in the Transdermal Treatment of Nicotine Addiction and Opioid Withdrawal Symptoms

Directory of Open Access Journals (Sweden)

Audra L. Stinchcomb

2009-01-01

Full Text Available Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual’s needs will increase patient compliance as well as provide much more efficient therapy. The purpose of this paper is to discuss the applicability of using carbon nanotube membranes in transdermal systems for treatment of drug abuse.

NMR characterisation and transdermal drug delivery potential of microemulsion systems

DEFF Research Database (Denmark)

Kreilgaard, Mads; Pedersen, E J; Jaroszewski, J W

2000-01-01

The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol/Plurol Isostearique/isostearylic isostearate/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride), and ...

Enhancing effect of negative polypropylene electret on in vitro transdermal delivery of cyclosporine A solution and its synergistic effect with ethyl oleate

International Nuclear Information System (INIS)

Cui, L L; Liu, H Y; Ma, L; Liang, Y Y; Guo, X; Jiang, J

2013-01-01

In this study, the corona charged electrets at voltages of −500 V, −1000 V and −2000 V were made from polypropylene (PP) film. The cyclosporine A (CsA) and 10% ethyl oleate were chosen as the model drug and chemical enhancer, respectively. The charge storage stability of the electrets and the in vitro transdermal behaviour of the model drug in solution under different conditions were studied. The results indicate that the external electrostatic field of the negative PP electrets could penetrate through the rat skin and enhance the transdermal delivery of cyclosporine A. A synergistic effect on enhancing the transdermal delivery of cyclosporine A was observed by combining different surface potential negative PP electrets with 10% ethyl oleate, and the amount of transdermal delivery of CsA was greatly increased comparing with only application of electrets. Therefore, the combination application of electret and chemical enhancer could be a feasible strategy in enhancing transdermal delivery of small peptide drugs or some large molecular drugs.

Patient-controlled analgesia: therapeutic interventions using transdermal electro-activated and electro-modulated drug delivery.

Science.gov (United States)

Indermun, Sunaina; Choonara, Yahya E; Kumar, Pradeep; Du Toit, Lisa C; Modi, Girish; Luttge, Regina; Pillay, Viness

2014-02-01

Chronic pain poses a major concern to modern medicine and is frequently undertreated, causing suffering and disability. Patient-controlled analgesia, although successful, does have limitations. Transdermal delivery is the pivot to which analgesic research in drug delivery has centralized, especially with the confines of needle phobias and associated pain related to traditional injections, and the existing limitations associated with oral drug delivery. Highlighted within is the possibility of further developing transdermal drug delivery for chronic pain treatment using iontophoresis-based microneedle array patches. A concerted effort was made to review critically all available therapies designed for the treatment of chronic pain. The drug delivery systems developed for this purpose and nondrug routes are elaborated on, in a systematic manner. Recent developments and future goals in transdermal delivery as a means to overcome the individual limitations of the aforementioned delivery routes are represented as well. The approval of patch-like devices that contain both the microelectronic-processing mechanism and the active medicament in a small portable device is still awaited by the pharmaceutical industry. This anticipated platform may provide transdermal electro-activated and electro-modulated drug delivery systems a feasible attempt in chronic pain treatment. Iontophoresis has been proven an effective mode used to administer ionized drugs in physiotherapeutic, diagnostic, and dermatological applications and may be an encouraging probability for the development of devices and aids in the treatment of chronic pain. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Transdermal and intradermal delivery of therapeutic agents: application of physical technologies

National Research Council Canada - National Science Library

Banga, Ajay K

2011-01-01

.... Advancements in science combined with the need for diverse drug delivery modalities have introduced a variety of transdermal and intradermal products for existing drugs at a fraction of the cost of new drug development...

Alfuzosin hydrochloride transdermal films: evaluation of physicochemical, in vitro human cadaver skin permeation and thermodynamic parameters

Directory of Open Access Journals (Sweden)

Satyanarayan Pattnaik

2009-12-01

Full Text Available Purpose: The main objective of the investigation was to develop a transdermal therapeutic system for alfuzosin hydrochloride and to study the effects of polymeric system and loading dose on the in vitro skin permeation pattern. Materials and methods: Principles of experimental design have been exploited to develop the dosage form. Ratio of ethyl cellulose (EC and polyvinyl pyrrolidone (PVP and loading dose were selected as independent variables and their influence on the cumulative amount of alfuzosin hydrochloride permeated per cm2 of human cadaver skin at 24 h (Q24, permeation flux (J and steady state permeability coefficient (P SS were studied using experimental design. Various physicochemical parameters of the transdermal films were also evaluated. Activation energy for in vitro transdermal permeation has been estimated. Results: Ratio of EC and PVP was found to be the main influential factor for all the dependent variables studied. Drug loading dose was also found to influence the dependent variables but to a lesser extent. Physicochemical parameters of the prepared films were evaluated and found satisfactory. Activation energy for alfuzosin permeation has also been estimated and reported. Conclusion: The therapeutic system was found to be dermatologically non-irritant and hence, a therapeutically effective amount of alfuzosin hydrochloride can be delivered via a transdermal route.

Superiority of liquid crystalline cubic nanocarriers as hormonal transdermal vehicle: comparative human skin permeation-supported evidence.

Science.gov (United States)

Mohyeldin, Salma M; Mehanna, Mohammed M; Elgindy, Nazik A

2016-08-01

The aim of this investigation was to explore the feasibility of various nanocarriers to enhance progesterone penetration via the human abdominal skin. Four progesterone-loaded nanocarriers; cubosomes, nanoliposomes, nanoemulsions and nanomicelles were formulated and characterized regarding particle size, zeta potential, % drug encapsulation and in vitro release. Structural elucidation of each nanoplatform was performed using transmission electron microscopy. Ex vivo skin permeation, deposition ability and histopathological examination were evaluated using Franz diffusion cells. Each nanocarrier was fabricated with a negative surface, nanometric size (≤ 270 nm), narrow size distribution and reasonable encapsulation efficiency. In vitro progesterone release showed a sustained release pattern for 24 h following a non-Fickian transport diffusion mechanism. All nanocarriers exhibited higher transdermal flux relative to free progesterone. Cubosomes revealed a higher skin penetration with transdermal steady flux of 48.57.10(-2) ± 0.7 µg/cm(2) h. Nanoliposomes offered a higher percentage of skin progesterone deposition compared to other nanocarriers. Based on the histopathological examination, cubosomes and nanoliposomes were found to be biocompatible for transdermal application. Confocal laser scanning microscopy confirmed the ability of fluoro-labeled cubosomes to penetrate through the whole skin layers. The elaborated cubosomes proved to be a promising non-invasive nanocarrier for transdermal hormonal delivery.

Ultradeformable Liposomes: a Novel Vesicular Carrier For Enhanced Transdermal Delivery of Procyanidins: Effect of Surfactants on the Formation, Stability, and Transdermal Delivery.

Science.gov (United States)

Chen, Rencai; Li, Rongli; Liu, Qian; Bai, Chao; Qin, Benlin; Ma, Yue; Han, Jing

2017-07-01

The aims of this work were to develop a novel vesicular carrier, procyanidins, ultradeformable liposomes (PUDLs), to expand the applications for procyanidins, and increase their stability and transdermal delivery. In this study, we prepared procyanidins ultradeformable liposomes using thin film hydration method and evaluated their encapsulation efficiency, vesicle deformability, storage stability, and skin permeation in vitro. The influence of different surfactants on the properties of PUDLs was also investigated. The results obtained showed that the PUDLs containing Tween 80 had a high entrapment efficiency (80.27 ± 0.99%), a small particle size (140.6 ± 19 nm), high elasticity, and prolonged drug release. Compared with procyanidins solution, the stability of procyanidins in PUDLs improved significantly when stored at 4, 25, and 30°C. The penetration rate of PUDLs was 6.25-fold greater than that of procyanidins solution. Finally, the results of our study suggested that PUDLs could increase the transdermal flux, prolong the release and improve the stability of procyanidins, and could serve as an effective dermal delivery system for procyanidins.

Transdermal delivery of scopolamine by natural submicron injectors: in-vivo study in pig.

Directory of Open Access Journals (Sweden)

Esther Shaoul

Full Text Available Transdermal drug delivery has made a notable contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. While transdermal delivery systems would appear to provide an attractive solution for local and systemic drug delivery, only a limited number of drugs can be delivered through the outer layer of the skin. The most difficult to deliver in this way are hydrophilic drugs. The aquatic phylum Cnidaria, which includes sea anemones, corals, jellyfish and hydra, is one of the most ancient multicellular phyla that possess stinging cells containing organelles (cnidocysts, comprising a sophisticated injection system. The apparatus is folded within collagenous microcapsules and upon activation injects a thin tubule that immediately penetrates the prey and delivers its contents. Here we show that this natural microscopic injection system can be adapted for systemic transdermal drug delivery once it is isolated from the cells and uploaded with the drug. Using a topically applied gel containing isolated natural sea anemone injectors and the muscarinic receptor antagonist scopolamine, we found that the formulated injectors could penetrate porcine skin and immediately deliver this hydrophilic drug. An in-vivo study in pigs demonstrated, for the first time, rapid systemic delivery of scopolamine, with T(max of 30 minutes and C(max 5 times higher than in controls treated topically with a scopolamine-containing gel without cnidocysts. The ability of the formulated natural injection system to penetrate a barrier as thick as the skin and systemically deliver an exogenous compound presents an intriguing and attractive alternative for hydrophilic transdermal drug delivery.

Transdermal glimepiride delivery system based on optimized ethosomal nano-vesicles: Preparation, characterization, in vitro, ex vivo and clinical evaluation.

Science.gov (United States)

Ahmed, Tarek A; El-Say, Khalid M; Aljaeid, Bader M; Fahmy, Usama A; Abd-Allah, Fathy I

2016-03-16

This work aimed to develop an optimized ethosomal formulation of glimepiride then loading into transdermal films to offer lower drug side effect, extended release behavior and avoid first pass effect. Four formulation factors were optimized for their effects on vesicle size (Y1), entrapment efficiency (Y2) and vesicle flexibility (Y3). Optimum desirability was identified and, an optimized formulation was prepared, characterized and loaded into transdermal films. Ex-vivo permeation study for the prepared films was conducted and, the permeation parameters and drug permeation mechanism were identified. Penetration through rat skin was studied using confocal laser microscope. In-vivo study was performed following transdermal application on human volunteers. The percent of alcohol was significantly affecting all the studied responses while the other factors and their interaction effects were varied on their effects on each response. The optimized ethosomal formulation showed observed values for Y1, Y2 and Y3 of 61 nm, 97.12% and 54.03, respectively. Ex-vivo permeation of films loaded with optimized ethosomal formulation was superior to that of the corresponding pure drug transdermal films and this finding was also confirmed after confocal laser microscope study. Permeation of glimepiride from the prepared films was in favor of Higushi-diffusion model and exhibited non-Fickian or anomalous release mechanism. In-vivo study revealed extended drug release behavior and lower maximum drug plasma level from transdermal films loaded with drug ethosomal formulation. So, the ethosomal formulation could be considered a suitable drug delivery system especially when loaded into transdermal vehicle with possible reduction in side effects and controlling the drug release. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of diclofenac prodrugs for enhancing transdermal delivery.

Science.gov (United States)

Lobo, Shabbir; Li, Henan; Farhan, Nashid; Yan, Guang

2014-03-01

Abstract Objective: The purpose of this study was to evaluate the approach of using diclofenac acid (DA) prodrugs for enhancing transdermal delivery. Methanol diclofenac ester (MD), ethylene glycol diclofenac ester (ED), glycerol diclofenac ester (GD) and 1,3-propylene glycol diclofenac ester (PD) were synthesized and evaluated for their physicochemical properties such as solubilities, octanol/water partition coefficients, stratum corneum/water partition coefficients, hydrolysis rates and bioconversion rates. In vitro fluxes across human epidermal membrane (HEM) in the Franz diffusion cell were determined on DA-, MD-, ED-, GD- and PD-saturated aqueous solutions. The formation of GD and ED led to the prodrugs with higher aqueous solubilities and lower partition coefficients than those of the parent drug. Prodrugs with improved aqueous solubility showed better fluxes across HEM in aqueous solution than that of the parent drug, with GD showing the highest aqueous solubility and also the highest flux. There is a linear relationship between the aqueous solubility and flux for DA, ED and PD, but GD and MD deviated from the linear line. Diclofenac prodrugs with improved hydrophilicity than the parent drug could be utilized for enhancing transdermal diclofenac delivery.

Evaluation of Diclofenac Prodrugs for Enhancing Transdermal Delivery

Science.gov (United States)

Lobo, Shabbir; Li, Henan; Farhan, Nashid; Yan, Guang

2016-01-01

The purpose of this study was to evaluate the approach of using diclofenac acid (DA) prodrugs for enhancing transdermal delivery. Methanol diclofenac ester (MD), ethylene glycol diclofenac ester (ED), glycerol diclofenac ester (GD), and 1,3-propylene glycol diclofenac ester (PD) were synthesized and evaluated for their physicochemical properties such as solubilities, octanol/water partition coefficients, stratum corneum/water partition coefficients, hydrolysis rates, and bioconversion rates. In vitro fluxes across human epidermal membrane (HEM) in Franz diffusion cell were determined on DA, MD, ED, GD, and PD saturated aqueous solutions. The formation of GD and ED led to the prodrugs with higher aqueous solubilities and lower partition coefficients than those of the parent drug. Prodrugs with improved aqueous solubility showed better fluxes across HEM in aqueous solution than that of the parent drug, with GD showing the highest aqueous solubility and also the highest flux. There is a linear relationship between the aqueous solubility and flux for DA, ED and PD, but GD and MD deviated from the linear line. Overall, diclofenac prodrugs with improved hydrophilicity than the parent drug could be utilized for enhancing transdermal diclofenac delivery. PMID:24517636

Design, development, physicochemical, and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt.

Science.gov (United States)

Arora, Priyanka; Mukherjee, Biswajit

2002-09-01

In this study, matrix-type transdermal patches containing diclofenac diethylamine were prepared using different ratios of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP and EC was casted on a polyvinylalcohol backing membrane. All the prepared formulations were subjected to physical studies (moisture content, moisture uptake, and flatness), in vitro release studies and in vitro skin permeation studies. In vitro permeation studies were performed across cadaver skin using a modified diffusion cell. Variations in drug release profiles among the formulations studied were observed. Based on a physicochemical and in vitro skin permeation study, formulation PA4 (PVP/EC, 1:2) and PA5 (PVP/EC, 1:5) were chosen for further in vivo experiments. The antiinflammatory effect and a sustaining action of diclofenac diethylamine from the two transdermal patches selected were studied by inducing paw edema in rats with 1% w/v carrageenan solution. When the patches were applied half an hour before the subplantar injection of carrageenan in the hind paw of male Wistar rats, it was observed that formulation PA4 produced 100% inhibition of paw edema in rats 12 h after carrageenan insult, whereas in the case of formulation PA5, 4% mean paw edema was obtained half an hour after the carrageenan injection and the value became 19.23% 12 h after the carrageenan insult. The efficacy of transdermal patches was also compared with the marketed Voveran gel and it was found that PA4 transdermal patches produced a better result as compared with the Voveran gel. Hence, it can be reasonably concluded that diclofenac diethylamine can be formulated into the transdermal matrix type patches to sustain its release characteristics and the polymeric composition (PVP/EC, 1:2) was found to be the best choice for manufacturing transdermal patches of diclofenac diethylamine among the formulations studied. Copyright 2002 Wiley-Liss, Inc.

Plasma Concentrations of Fentanyl Achieved With Transdermal Application in Chickens

NARCIS (Netherlands)

Delaski, Kristina M; Gehring, Ronette; Heffron, Brendan T; Negrusz, Adam; Gamble, Kathryn C

2017-01-01

Providing appropriate analgesia is an important concern in any species. Fentanyl, a μ-receptor specific opioid, use is common in mammalian species but has been incompletely evaluated for this purpose in avian species. Transdermal fentanyl patches were applied to domestic chickens (n = 10) of varying

Evaluation of Diclofenac Prodrugs for Enhancing Transdermal Delivery

OpenAIRE

Lobo, Shabbir; Li, Henan; Farhan, Nashid; Yan, Guang

2013-01-01

The purpose of this study was to evaluate the approach of using diclofenac acid (DA) prodrugs for enhancing transdermal delivery. Methanol diclofenac ester (MD), ethylene glycol diclofenac ester (ED), glycerol diclofenac ester (GD), and 1,3-propylene glycol diclofenac ester (PD) were synthesized and evaluated for their physicochemical properties such as solubilities, octanol/water partition coefficients, stratum corneum/water partition coefficients, hydrolysis rates, and bioconversion rates. ...

Evaluation of paeonol-loaded transethosomes as transdermal delivery carriers.

Science.gov (United States)

Chen, Z X; Li, B; Liu, T; Wang, X; Zhu, Y; Wang, L; Wang, X H; Niu, X; Xiao, Y; Sun, Q

2017-03-01

Paeonol shows effective anti-allergic, anti-inflammatory and analgesic activities. However, because of its poor solubility in water and high volatility at room temperature, the application of this drug is restricted in the clinic. The objective of this research was to develop a biocompatible paeonol formulation with improved stability, skin delivery and pharmacokinetic efficiency. In this paper, paeonol-loaded vesicles were prepared using an ethanol injection method. Nano-vesicles were characterized for their physical properties and encapsulation efficiency (EE). Drug permeation behavior in vitro and deposition quantity in porcine ear skin were measured with a Valia-Chien (V-C) diffusion device. Additionally, a validated and sensitive high performance liquid chromatography (HPLC) method was developed to analyze paeonol concentrations in rat plasma after transdermal administration. The results showed that the particle-size order of the nano-vesicles was the following: transethosomes (122.5±7.5nm)transethosomes had a higher EE (85.5±5.2%), and they showed a spherical morphology with a smooth surface when viewed under a transmission electron microscope (TEM). In an in vitro permeation study, the paeonol transethosomes showed an enhanced transdermal flux of 95.7±8.8μg/cm 2 /h and a higher deposition quantity in porcine ear skin compared to the transfersomes. A one-compartment first-order absorption model could be used to describe the pharmacokinetics of paeonol in rats after transdermal administration. The AUC of the paeonol transethosomes was approximately 1.57- and 3.52-fold higher than those of the transfersomes and a saturated solution of paeonol in 35% ethanol, respectively. The results demonstrated that the paeonol transethosomes had a narrow size distribution, high encapsulation efficiency, and long residence in the plasma. This formulation remarkably enhanced the bioavailability of paeonol. Copyright © 2016 Elsevier B.V. All rights reserved.

The importance of microjet vs shock wave formation in sonophoresis.

Science.gov (United States)

Wolloch, Lior; Kost, Joseph

2010-12-01

Low-frequency ultrasound application has been shown to greatly enhance transdermal drug delivery. Skin exposed to ultrasound is affected in a heterogeneous manner, thus mass transport through the stratum corneum occurs mainly through highly permeable localized transport regions (LTRs). Shock waves and microjets generated during inertial cavitations are responsible for the transdermal permeability enhancement. In this study, we evaluated the effect of these two phenomena using direct and indirect methods, and demonstrated that the contribution of microjets to skin permeability enhancement is significantly higher than shock waves. Copyright © 2010. Published by Elsevier B.V.

Hybrid electrospun chitosan-phospholipids nanofibers for transdermal drug delivery.

Science.gov (United States)

Mendes, Ana C; Gorzelanny, Christian; Halter, Natalia; Schneider, Stefan W; Chronakis, Ioannis S

2016-08-20

Chitosan (Ch) polysaccharide was mixed with phospholipids (P) to generate electrospun hybrid nanofibers intended to be used as platforms for transdermal drug delivery. Ch/P nanofibers exibithed average diameters ranging from 248±94nm to 600±201nm, depending on the amount of phospholipids used. Fourier Transformed Infra-Red (FTIR) spectroscopy and Dynamic Light Scattering (DLS) data suggested the occurrence of electrostatic interactions between amine groups of chitosan with the phospholipid counterparts. The nanofibers were shown to be stable for at least 7days in Phosphate Buffer Saline (PBS) solution. Cytotoxicity studies (WST-1 and LDH assays) demonstrated that the hybrid nanofibers have suitable biocompatibility. Fluorescence microscopy, also suggested that L929 cells seeded on top of the CH/P hybrid have similar metabolic activity comparatively to the cells seeded on tissue culture plate (control). The release of curcumin, diclofenac and vitamin B12, as model drugs, from Ch/P hybrid nanofibers was investigated, demonstrating their potential utilization as a transdermal drug delivery system. Copyright © 2016 Elsevier B.V. All rights reserved.

In vivo studies of transdermal nanoparticle delivery with microneedles using photoacoustic microscopy

Science.gov (United States)

Moothanchery, Mohesh; Seeni, Razina Z.; Xu, Chenjie; Pramanik, Manojit

2017-01-01

Microneedle technology allows micron-sized conduits to be formed within the outermost skin layers for both localized and systemic delivery of therapeutics including nanoparticles. Histological methods are often employed for characterization, and unfortunately do not allow for the in vivo visualization of the delivery process. This study presents the utilization of optical resolution-photoacoustic microscopy to characterize the transdermal delivery of nanoparticles using microneedles. Specifically, we observe the in vivo transdermal delivery of gold nanoparticles using microneedles in mice ear and study the penetration, diffusion, and spatial distribution of the nanoparticles in the tissue. The promising results reveal that photoacoustic microscopy can be used as a potential imaging modality for the in vivo characterization of microneedles based drug delivery. PMID:29296482

PMO Delivery System Using Bubble Liposomes and Ultrasound Exposure for Duchenne Muscular Dystrophy Treatment.

Science.gov (United States)

Negishi, Yoichi; Ishii, Yuko; Nirasawa, Kei; Sasaki, Eri; Endo-Takahashi, Yoko; Suzuki, Ryo; Maruyama, Kazuo

2018-01-01

Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration, caused by nonsense or frameshift mutations in the dystrophin (DMD) gene. Antisense oligonucleotides can be used to induce specific exon skipping; recently, a phosphorodiamidate morpholino oligomer (PMO) has been approved for clinical use in DMD. However, an efficient PMO delivery strategy is required to improve the therapeutic efficacy in DMD patients. We previously developed polyethylene glycol (PEG)-modified liposomes containing ultrasound contrast gas, "Bubble liposomes" (BLs), and found that the combination of BLs with ultrasound exposure is a useful gene delivery tool. Here, we describe an efficient PMO delivery strategy using the combination of BLs and ultrasound exposure to treat muscles in a DMD mouse model (mdx). This ultrasound-mediated BL technique can increase the PMO-mediated exon-skipping efficiency, leading to significantly increased dystrophin expression. Thus, the combination of BLs and ultrasound exposure may be a feasible PMO delivery method to improve therapeutic efficacy and reduce the PMO dosage for DMD treatment.

Drug profile: transdermal rivastigmine patch in the treatment of Alzheimer disease.

Science.gov (United States)

Emre, Murat; Bernabei, Roberto; Blesa, Rafael; Bullock, Roger; Cunha, Luis; Daniëls, Hugo; Dziadulewicz, Edward; Förstl, Hans; Frölich, Lutz; Gabryelewicz, Tomasz; Levin, Oleg; Lindesay, James; Martínez-Lage, Pablo; Monsch, Andreas; Tsolaki, Magda; van Laar, Teus

2010-08-01

Cholinesterase inhibitors constitute one of the mainstays of treatment of Alzheimer disease (AD). Gastrointestinal side effects, difficulty accessing therapeutic doses and poor patient compliance have been identified as barriers to effective treatment with these substances. The rivastigmine transdermal patch provides continuous delivery of drug through the skin into the bloodstream, avoiding the fluctuations in plasma concentration associated with oral administration. This pharmacokinetic profile is associated with reduced side effects, resulting in easier access to expected target doses. These benefits, along with other practical advantages of the transdermal patch, may contribute to enhanced patient compliance. Here, we present a review of the current literature on rivastigmine patch, and offer advice based on our own collective clinical experience. Rivastigmine patch provides an efficient option for managing patients with AD, to be considered among the first line therapies for the disease.

Transdermal Physostigmine—Absence of Effect on Topographic Brain Mapping

Directory of Open Access Journals (Sweden)

M. Y. Neufeld

1993-01-01

Full Text Available Nine patients with primary degenerative dementia (PDD participated in an open trial of transdermal physostigmine (TPh. In order to evaluate the neurophysiologic effects of TPh, EEG data were recorded and compared at baseline and following 2 months of continuous treatment. There was no significant effect of TPh on EEG spectra in patients with PDD.

Improvement in transdermal drug delivery performance by graphite oxide/temperature-responsive hydrogel composites with micro heater

International Nuclear Information System (INIS)

Yun, Jumi; Lee, Dae Hoon; Im, Ji Sun; Kim, Hyung-Il

2012-01-01

Transdermal drug delivery system (TDDS) was prepared with temperature-responsive hydrogel. The graphite was oxidized and incorporated into hydrogel matrix to improve the thermal response of hydrogel. The micro heater was fabricated to control the temperature precisely by adopting a joule heating method. The drug in hydrogel was delivered through a hairless mouse skin by controlling temperature. The efficiency of drug delivery was improved obviously by incorporation of graphite oxide due to the excellent thermal conductivity and the increased interfacial affinity between graphite oxide and hydrogel matrix. The fabricated micro heater was effective in controlling the temperature over lower critical solution temperature of hydrogel precisely with a small voltage less than 1 V. The cell viability test on graphite oxide composite hydrogel showed enough safety for using as a transdermal drug delivery patch. The performance of TDDS could be improved noticeably based on temperature-responsive hydrogel, thermally conductive graphite oxide, and efficient micro heater. - Graphical abstract: The high-performance transdermal drug delivery system could be prepared by combining temperature-responsive hydrogel, thermally conductive graphite oxide with improved interfacial affinity, and efficient micro heater fabricated by a joule heating method. Highlights: ► High performance of transdermal drug delivery system with an easy control of voltage. ► Improved thermal response of hydrogel by graphite oxide incorporation. ► Efficient micro heater fabricated by a joule heating method.

The Effect of Transdermal Scopolamine for the Prevention of Postoperative Nausea and Vomiting

Directory of Open Access Journals (Sweden)

Maria A. Antor

2014-04-01

Full Text Available Postoperative nausea and vomiting is one of the most common and undesirable complaints recorded in as many as 70%-80% of high-risk surgical patients. The current prophylactic therapy recommendations for PONV management stated in the Society of Ambulatory Anesthesia guidelines should start with monotherapy and patients at moderate to high risk, a combination of antiemetic medication should be considered. Consequently, if rescue medication is required, the antiemetic drug chosen should be from a different therapeutic class and administration mode than the drug used for prophylaxis. The guidelines restrict the use of dexamethasone, transdermal scopolamine, aprepitant, and palonosetron as rescue medication 6 hours after surgery. In an effort to find a safer and reliable therapy for postoperative nausea and vomiting, new drugs with antiemetic properties and minimal side effects are needed, and scopolamine may be considered an effective alternative. Scopolamine is a belladonna alkaloid, α-(hydroxymethyl benzene acetic acid 9-methyl-3-oxa-9-azatricyclo non-7-yl ester, acting as a nonselective muscarinic antagonist and producing both peripheral antimuscarinic and central sedative, antiemetic, and amnestic effects. The empirical formula is C17H21NO4 and its structural formula is a tertiary amine L-(2-scopolamine (tropic acid ester with scopine; MW = 303.4. Scopolamine became the first drug commercially available as a transdermal therapeutic system used for extended continuous drug delivery during 72 hours. Clinical trials with transdermal scopolamine have consistently demonstrated its safety and efficacy in postoperative nausea and vomiting. Thus, scopolamine is a promising candidate for the management of postoperative nausea and vomiting in adults as a first line monotherapy or in combination with other drugs. In addition, transdermal scopolamine might be helpful in preventing postoperative discharge nausea and vomiting owing to its long

Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling, characterization, and ex vivo skin permeation.

Science.gov (United States)

Abdel Messih, Hanaa A; Ishak, Rania A H; Geneidi, Ahmed S; Mansour, Samar

2017-06-01

The aim of the present work is to exclusively optimize and model the effect of phospholipid type either egg phosphatidylcholine (EPC) or soybean phosphatidylcholine (SPC), together with other formulation variables, on the development of nano-ethosomal systems for transdermal delivery of a water-soluble antiemetic drug. Tropisetron HCl (TRO) is available as hard gelatin capsules and IV injections. The transdermal delivery of TRO is considered as a novel alternative route supposing to improve BAV as well as patient convenience. TRO-loaded ethanolic vesicular systems were prepared by hot technique. The effect of formulation variables were optimized through a response surface methodology using 3 × 2 2 -level full factorial design. The concentrations of both PC (A) and ethanol (B) and PC type (C) were the factors, while entrapment efficiency (Y 1 ), vesicle size (Y 2 ), polydispersity index (Y 3 ), and zeta potential (Y 4 ) were the responses. The drug permeation across rat skin from selected formulae was studied. Particle morphology, drug-excipient interactions, and vesicle stability were also investigated. The results proved the critical role of all formulation variables on ethosomal characteristics. The suggested models for all responses showed good predictability. Only the concentration of phospholipid, irrespective to PC type, had a significant effect on the transdermal flux (p transdermal TRO delivery.

Development of Flexible Capacitive Ultrasound Transducers and the Use of Ultrasound for Bone Repair

Science.gov (United States)

Wentzell, Scott A.

devices have the potential to mediate both bone resorption and deposition, and also provide a new functional system for generating ultrasound on the irregular surfaces encountered in clinical settings.

Life-threatening coma and full-thickness sunburn in a patient treated with transdermal fentanyl patches: a case report

Directory of Open Access Journals (Sweden)

Sindali Katia

2012-07-01

Full Text Available Abstract Introduction Fentanyl transdermal patches have been widely used in the treatment of chronic pain and in palliative care settings since 1991 in cases where prolonged opioid use is often necessary. Transdermal drug delivery is deemed safe and effective with the advantages of delivering a steady dose of the drug and improving patient compliance due to its ease of use. However, intentional and unintentional misuse and overdose using transdermal opioid patches has been widely reported in the literature. Case presentation We describe the case of a 77-year-old Caucasian woman who developed severe opioid toxicity while sun tanning, likely due to altered fentanyl transdermal patch function in a heated environment. As a result of prolonged sun exposure due to an opioid-induced coma she then sustained hyperthermia and severe burns to her abdomen and lower limbs. This inadvertent fentanyl overdose necessitated initial treatment in intensive care and follow on care in a specialist burn unit. Conclusion Patients who are using fentanyl patches and their relatives should be educated about how to use the patch safely. Healthcare practitioners should warn patients about the possibility of overdosing on transdermally delivered drugs if used incorrectly. They should avoid strenuous activities and external heat sources such as warming blankets, hot water bottles, saunas, hot tubs or sunbathing and should seek medical attention if they develop a fever. Additionally, any burns sustained in the context of altered consciousness levels such as in this case with opioid overdose should raise suspicion about a potential deeper burn injury than is usually observed.

Transdermal testosterone replacement therapy in men

Directory of Open Access Journals (Sweden)

Ullah MI

2014-01-01

Full Text Available M Iftekhar Ullah,1 Daniel M Riche,1,2 Christian A Koch1,31Department of Medicine, University of Mississippi Medical Center, 2Department of Pharmacy Practice, The University of Mississippi, 3GV (Sonny Montgomery VA Medical Center, Jackson, MS, USAAbstract: Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule.Keywords: hypogonadism, transdermal, testosterone, sexual function, testosterone replacement therapy, estradiol

Use of electroporation and reverse iontophoresis for extraction of transdermal multibiomarkers

Directory of Open Access Journals (Sweden)

Ching CTS

2012-02-01

Full Text Available Congo Tak-Shing Ching1,2, Lin-Shien Fu3-5, Tai-Ping Sun1, Tzu-Hsiang Hsu1, Kang-Ming Chang21Department of Electrical Engineering, National Chi Nan University, Puli, Nantou County, 2Department of Photonics and Communication Engineering, Asia University, Wufeng, Taichung, 3Department of Pediatrics, National Yang Ming University, Taipei, 4Institute of Technology, National Chi Nan University, Puli, 5Department of Pediatrics, Taichung Veterans General Hospital, Taichung City, TaiwanBackground: Monitoring of biomarkers, like urea, prostate-specific antigen (PSA, and osteopontin, is very important because they are related to kidney disease, prostate cancer, and ovarian cancer, respectively. It is well known that reverse iontophoresis can enhance transdermal extraction of small molecules, and even large molecules if reverse iontophoresis is used together with electroporation. Electroporation is the use of a high-voltage electrical pulse to create nanochannels within the stratum corneum, temporarily and reversibly. Reverse iontophoresis is the use of a small current to facilitate both charged and uncharged molecule transportation across the skin. The objectives of this in vitro study were to determine whether PSA and osteopontin are extractable transdermally and noninvasively and whether urea, PSA, and osteopontin can be extracted simultaneously by electroporation and reverse iontophoresis.Methods: All in vitro experiments were conducted using a diffusion cell assembled with the stratum corneum of porcine skin. Three different symmetrical biphasic direct currents (SBdc, five various electroporations, and a combination of the two techniques were applied to the diffusion cell via Ag/AgCl electrodes. The three different SBdc had the same current density of 0.3 mA/cm2, but different phase durations of 0 (ie, no current, control group, 30, and 180 seconds. The five different electroporations had the same pulse width of 1 msec and number of pulses per second

Comparison of estrus synchronization by controlled internal drug release device (CIDR) and adhesive transdermal progestin patch in postpartum beef cows.

Science.gov (United States)

Kajaysri, Jatuporn; Chumchoung, Chaiwat; Wutthiwitthayaphong, Supphathat; Suthikrai, Wanvipa; Sangkamanee, Praphai

2017-09-15

Estrous synchronization with progesterone based protocols has been essentially used in cattle industry. Although intravaginal devices have been commonly used, this technique may induce vaginitis. This study aimed at examining the efficiency of novel transdermal progestin patch on follicle development and comparing the progestin patch versus CIDR device on estrous synchronization, complication at treated site and pregnancy in beef cattle. In experiment 1, seven beef cows were treated with an adhesive transdermal progestin patch on the ventral surface of the proximal part of the tail for 7 days. The cows were daily examined the follicular development using ultrasonography starting on Day 0 till 3 days after hormone removal. Experiment 2, forty beef cows were divided into two equal groups (20 cows per group). The cows randomly allocated to received either vaginal insertion of CIDR (n = 20) or treated with an adhesive transdermal progestin patch (n = 20). The levels of plasma progesterone during the experiment and the numbers of standing estrous cows were recorded. Timed artificial inseminated (TAI) was performed at 60 h after CIDR or patch termination. Pregnancy rates were determined at 60 days after TAI. Experiment 1 revealed that the novel transdermal progestin patch could efficiently control follicular growth. All the seven treated cows had dominant follicle upon dermal patch removal indicating the effectiveness of the progestin patch. In experiment 2, the percentages of cows exhibited standing estrus were similar between transdermal patch (72.22%) and CIDR (70.00%). The levels of plasma progesterone during CIDR treatment were significantly higher (4.06 ± 1.65 ng/mL on Day 1 and 3.62 ± 1.60 ng/mL on Day 7) compared with transdermal patch (2.60 ± 1.43 ng/mL on Day 1 and 1.81 ± 1.57 ng/mL on Day 7). Three cows treated with CIDR (15%) developed vaginitis while none of cows had physically dermal reaction at adhesive site. Cows synchronized with

Preparation and the Biopharmaceutical Evaluation for the Metered Dose Transdermal Spray of Dexketoprofen

Science.gov (United States)

Luo, Huafei; Zhu, Zhuangzhi; Wu, Yubo; Luo, Jing; Wang, Hao

2014-01-01

The objective of the present work was to develop a metered dose transdermal spray (MDTS) formulation for transdermal delivery of dexketoprofen (DE). DE release from a series of formulations was assessed in vitro. Various qualitative and quantitative parameters like spray pattern, pump seal efficiency test, average weight per metered dose, and dose uniformity were evaluated. The optimized formulation with good skin permeation and an appropriate drug concentration and permeation enhancer (PE) content was developed incorporating 7% (w/w, %) DE, 7% (v/v, %) isopropyl myristate (IPM), and 93% (v/v, %) ethanol. In vivo pharmacokinetic study indicated that the optimized formulation showed a more sustainable plasma-concentration profile compared with the Fenli group. The antiinflammatory effect of DE MDTS was evaluated by experiments involving egg-albumin-induced paw edema in rats and xylene-induced ear swelling in mice. Acetic acid-induced abdominal constriction was used to evaluate the anti-nociceptive actions of DE MDTS. Pharmacodynamic studies indicated that the DE MDTS has good anti-inflammatory and anti-nociceptive activities. Besides, skin irritation studies were performed using rat as an animal model. The results obtained show that the MDTS can be a promising and innovative therapeutic system used in transdermal drug delivery for DE. PMID:24660066

Preparation and the Biopharmaceutical Evaluation for the Metered Dose Transdermal Spray of Dexketoprofen

Directory of Open Access Journals (Sweden)

Wangding Lu

2014-01-01

Full Text Available The objective of the present work was to develop a metered dose transdermal spray (MDTS formulation for transdermal delivery of dexketoprofen (DE. DE release from a series of formulations was assessed in vitro. Various qualitative and quantitative parameters like spray pattern, pump seal efficiency test, average weight per metered dose, and dose uniformity were evaluated. The optimized formulation with good skin permeation and an appropriate drug concentration and permeation enhancer (PE content was developed incorporating 7% (w/w, % DE, 7% (v/v, % isopropyl myristate (IPM, and 93% (v/v, % ethanol. In vivo pharmacokinetic study indicated that the optimized formulation showed a more sustainable plasma-concentration profile compared with the Fenli group. The antiinflammatory effect of DE MDTS was evaluated by experiments involving egg-albumin-induced paw edema in rats and xylene-induced ear swelling in mice. Acetic acid-induced abdominal constriction was used to evaluate the anti-nociceptive actions of DE MDTS. Pharmacodynamic studies indicated that the DE MDTS has good anti-inflammatory and anti-nociceptive activities. Besides, skin irritation studies were performed using rat as an animal model. The results obtained show that the MDTS can be a promising and innovative therapeutic system used in transdermal drug delivery for DE.

Transdermal delivery of angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs) and others for management of hypertension.

Science.gov (United States)

Ahad, Abdul; Al-Mohizea, Abdullah Mohammed; Al-Jenoobi, Fahad Ibrahim; Aqil, Mohd

2016-01-01

Angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs) are some of the most commonly prescribed medications for hypertension. Most of all conventional dosage forms of ARBs and ACEIs undergo extensive first-pass metabolism, which significantly reduces bioavailability. Majority of ARBs and ACEIs are inherently short acting due to a rapid elimination half-life. In addition, oral dosage forms of ARBs and ACEIs have many high incidences of adverse effects due to variable absorption profiles, higher frequency of administration and poor patient compliance. Many attempts have been made globally at the laboratory level to investigate the skin permeation and to develop transdermal therapeutic systems of various ARBs, ACEIs and other anti-hypertensives, to circumvent the drawbacks associated with their conventional dosage form. This manuscript presents an outline of the transdermal research specifically in the area of ARBs, ACEIs and other anti-hypertensives reported in various pharmaceutical journals. The transdermal delivery has gained a significant importance for systemic treatment as it is able to avoid first-pass metabolism and major fluctuations of plasma levels typical of repeated oral administration. As we can experience from this review article that transdermal delivery of different ARBs and ACEIs improves bioavailability as well as patient compliance by many folds. In fact, the rationale development of some newer ARBs, ACEIs and other anti-hypertensives transdermal systems will provide new ways of treatment, circumventing current limitations for conventional dosage forms.

Pharmacodynamics of transdermal granisetron in women with nausea and vomiting of pregnancy.

Science.gov (United States)

Caritis, Steve; Zhao, Yang; Chen, Hui-Jun; Venkataramanan, Raman

2016-07-01

Limited options exist for women with nausea and vomiting of pregnancy (NVP) who cannot tolerate oral intake. Transdermal delivery of granisetron, a 5-hydroxytryptamine-3 receptor antagonist, provides an effective alternative for such patients. The objective of this study was to evaluate the pharmacodynamics of granisetron administered intravenously (IV) and as a sustained release transdermal patch in women with NVP. We recruited 16 women with singleton gestation between 12 0/7-18 6/7 weeks who were receiving treatment for NVP and had a Pregnancy Unique Quantification of Emesis and Nausea (PUQE) score of ≥6. All consenting subjects received 1 mg of granisetron as an IV infusion over 5 minutes and blood was obtained prior to the infusion and at 10, 20, 30, and 60 minutes and at 2, 4, 6, 8, 12, and 24 hours after the start of the infusion. After a minimum washout of 48 hours after initiation of IV granisetron, a 52-cm(2) granisetron patch (34.3 mg) was placed on the upper arm of all subjects for 7 days. Blood was drawn prior to patch placement and daily thereafter for 9 days. The subjects were evaluated daily. The PUQE score was obtained from these subjects prior to the IV infusion and daily for 2 days after and again prior to and daily for 9 days after patch placement. Complete data were available in 15 women after IV administration and 13 women after patch placement. One woman stopped participation during the IV infusion while data were not available in 2 additional women after patch placement due to noncompliance. Peak plasma granisetron concentrations after IV and transdermal administration were similar (∼10 ng/mL). Prior to IV administration of granisetron, the PUQE score was 8.6 ± 1.8 (mean ± SD). The PUQE scores were significantly reduced for the ensuing 2 days (P Granisetron significantly improved symptoms of nausea and vomiting as gauged by the PUQE score. After IV infusion the reduction in PUQE score was observed within 1 day. When granisetron was

Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs.

Science.gov (United States)

Banks, Stan L; Pinninti, Raghotham R; Gill, Harvinder S; Paudel, Kalpana S; Crooks, Peter A; Brogden, Nicole K; Prausnitz, Mark R; Stinchcomb, Audra L

2010-07-01

Controlled-release delivery of 6-beta-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. MN pore lifetime was estimated by pharmacokinetic evaluation, transepidermal water loss (TEWL) and visualization of MN-treated skin pore diameters using light microscopy. A 3.6-fold enhancement in steady-state plasma concentration was observed in vivo with MN treated skin with NTXOL.HCl, as compared to NTXOL base. TEWL measurements and microscopic evaluation of stained MN-treated guinea pig skin indicated the presence of pores, suggesting a feasible nonlipid bilayer pathway for enhanced transdermal delivery. Overall, MN-assisted transdermal delivery appears viable for at least 48 h after MN-application. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

The role of transdermal estrogen sprays and estradiol topical emulsion in the management of menopause-associated vasomotor symptoms

Directory of Open Access Journals (Sweden)

Amy M Egras

2010-05-01

Full Text Available Amy M Egras, Elena M UmlandJefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, PA, USAAbstract: Vasomotor symptoms (VMS are among the most bothersome complaints of postmenopausal women. To date, the most widely studied and effective treatment for VMS is hormone replacement therapy, consisting of estrogen (in women without a uterus or estrogen plus progestin (in women with a uterus. Traditionally, oral estrogens have been used for treatment. However, over the years, additional estrogen formulations have been developed including transdermal patches; vaginal rings, creams, and tablets; and injectable preparations. Two newer formulations are transdermal estrogen spray and estradiol topical emulsion. This review evaluates the current literature assessing the use of these two newer formulations for the treatment of VMS associated with menopause.Keywords: menopause, vasomotor symptoms, transdermal estrogen spray, estradiol topical emulsion

Diclofenac Potassium Transdermal Patches Using Natural Rubber Latex Biomembranes as Carrier

Directory of Open Access Journals (Sweden)

Natan Roberto de Barros

2015-01-01

Full Text Available The aim of this study was to design a compound transdermal patch containing diclofenac potassium (Dic-K using natural rubber latex (NRL biomembrane. The NRL from Hevea brasiliensis is easily manipulated and low cost and presents high mechanical resistance. It is a biocompatible material which can stimulate natural angiogenesis and is capable of adhering cells on its surface. Recent researches have used the NRL for Transdermal Drug Delivery Systems (TDDSs. Dic-K is used for the treatment of rheumatoid arthritis and osteoarthritis and pain relief for postoperative and posttraumatic cases, as well as inflammation and edema. Results showed that the biomembrane can release Dic-K for up to 216 hours. The kinetics of the Dic-K release could be fitted with double exponential function. X-ray diffraction and Fourier Transform Infrared (FTIR spectroscopy show some interaction by hydrogen bound. The results indicated the potential of the compound patch.

Physical, chemical and biological studies of gelatin/chitosan based transdermal fims with embedded silver nanoparticles

Directory of Open Access Journals (Sweden)

Sneha Paul

2015-12-01

Full Text Available Objective: To study the physical, chemical and biological properties of composite chitosangelatin transdermal film along with silver nanoparticles as binding agent and determine the compatibility of the prepared amalgamation towards wound management. Methods: Transdermal film preparations were done by solvent casting method containing different concentrations of biological synthesized silver nanoparticles. The films were characterized by using scanning electron microscope for their morphology and the determination of silver metal was done by using inductively coupled plasma atomic emission spectroscopy. Then a quantity of silver nanoparticles was further proceeded by physiochemical parameters (weight, thickness, temperature, solubility, absorption, tensile strength, in vitro drug release and skin permeation and biological parameters studies (anti-microbial, cytotoxicity and reactive oxygen species. Results: The film prepared by utilizing 2 g of gelatin and 0.5 g of chitosan exhibited better results. The physiochemical parameters studies revealed higher concentration of silver nanoparticles would give better results. In vitro drug release studies through dialysis and skin permeation showed the release of drug versus time (h. These films had shown excellent inhibition against Streptococcus and Escherichia coli species. Cytotoxicity study by MTT indicated the mild toxicity existed as the concentration of silver nanoparticles increased. Reactive oxygen species generation studies of transdermal film by using 2'7'-dichlorofluorescein diacetate assay demonstrated that the fluorescent cells were found in the higher concentration, which indicated cell damage (reactive oxygen species generated. Conclusions: Based on these observations, in vitro performances against various characteristics of transdermal film, would be utilized as a distinct dressing material and patches accessible in market.

Improvement in transdermal drug delivery performance by graphite oxide/temperature-responsive hydrogel composites with micro heater

Energy Technology Data Exchange (ETDEWEB)

Yun, Jumi [Department of Fine Chemical Engineering and Applied Chemistry, BK21-E2M, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Lee, Dae Hoon [Environment Research Division, Korea Institute of Machinery and Materials, 171 Jang-dong, Yusong-gu, Daejeon 305-343 (Korea, Republic of); Im, Ji Sun [Department of Fine Chemical Engineering and Applied Chemistry, BK21-E2M, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Kim, Hyung-Il, E-mail: hikim@cnu.ac.kr [Department of Fine Chemical Engineering and Applied Chemistry, BK21-E2M, Chungnam National University, Daejeon 305-764 (Korea, Republic of)

2012-08-01

Transdermal drug delivery system (TDDS) was prepared with temperature-responsive hydrogel. The graphite was oxidized and incorporated into hydrogel matrix to improve the thermal response of hydrogel. The micro heater was fabricated to control the temperature precisely by adopting a joule heating method. The drug in hydrogel was delivered through a hairless mouse skin by controlling temperature. The efficiency of drug delivery was improved obviously by incorporation of graphite oxide due to the excellent thermal conductivity and the increased interfacial affinity between graphite oxide and hydrogel matrix. The fabricated micro heater was effective in controlling the temperature over lower critical solution temperature of hydrogel precisely with a small voltage less than 1 V. The cell viability test on graphite oxide composite hydrogel showed enough safety for using as a transdermal drug delivery patch. The performance of TDDS could be improved noticeably based on temperature-responsive hydrogel, thermally conductive graphite oxide, and efficient micro heater. - Graphical abstract: The high-performance transdermal drug delivery system could be prepared by combining temperature-responsive hydrogel, thermally conductive graphite oxide with improved interfacial affinity, and efficient micro heater fabricated by a joule heating method. Highlights: Black-Right-Pointing-Pointer High performance of transdermal drug delivery system with an easy control of voltage. Black-Right-Pointing-Pointer Improved thermal response of hydrogel by graphite oxide incorporation. Black-Right-Pointing-Pointer Efficient micro heater fabricated by a joule heating method.

Enhancement of the bioavailability of an antihypertensive drug by transdermal protransfersomal system: formulation and in vivo study.

Science.gov (United States)

Morsi, Nadia M; Aboelwafa, Ahmed A; Dawoud, Marwa H S

2018-06-01

Timolol Maleate (TiM), a nonselective β-adrenergic blocker, is a potent highly effective agent for management of hypertension. The drug suffers from poor oral bioavailability (50%) due to its first pass effect and a short elimination half-life of 4 h; resulting in its frequent administration. Transdermal formulation may circumvent these problems in the form of protransfersomes. The aim of this study is to develop and optimize transdermal protransfersomal system of Timolol Maleate by film deposition on carrier method where protransfersomes were converted to transfersomes upon skin hydration following transdermal application under occlusive conditions. Two 2 3 full factorial designs were employed to investigate the influence of three formulation variables which were; phosphatidyl choline: surfactant molar ratio, carrier: mixture and the type of SAA each on particle size, drug entrapment efficiency and release rate. The optimized formulation was evaluated regarding permeation through hairless rat skin and compared with oral administration of aqueous solution on male Wistar rats. Optimized protransfersomal system had excellent permeation rate through shaved rat skin (780.69 μg/cm 2 /h) and showed six times increase in relative bioavailability with prolonged plasma profile up to 72 h. A potential protransfresomal transdermal system was successfully developed and factorial design was found to be a smart tool in its optimization.

A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin.

Science.gov (United States)

Seong, Keum-Yong; Seo, Min-Soo; Hwang, Dae Youn; O'Cearbhaill, Eoin D; Sreenan, Seamus; Karp, Jeffrey M; Yang, Seung Yun

2017-11-10

Proteins are important biologic therapeutics used for the treatment of various diseases. However, owing to low bioavailability and poor skin permeability, transdermal delivery of protein therapeutics poses a significant challenge. Here, we present a new approach for transdermal protein delivery using bullet-shaped double-layered microneedle (MN) arrays with water-swellable tips. This design enabled the MNs to mechanically interlock with soft tissues by selective distal swelling after skin insertion. Additionally, prolonged release of loaded proteins by passive diffusion through the swollen tips was obtained. The bullet-shaped MNs provided an optimal geometry for mechanical interlocking, thereby achieving significant adhesion strength (~1.6Ncm -2 ) with rat skin. By harnessing the MN's reversible swelling/deswelling property, insulin, a model protein drug, was loaded in the swellable tips using a mild drop/dry procedure. The insulin-loaded MN patch released 60% of insulin when immersed in saline over the course of 12h and approximately 70% of the released insulin appeared to have preserved structural integrity. An in vivo pilot study showed a prolonged release of insulin from swellable MN patches, leading to a gradual decrease in blood glucose levels. This self-adherent transdermal MN platform can be applied to a variety of protein drugs requiring sustained release kinetics. Copyright © 2017 Elsevier B.V. All rights reserved.

Cardiac Gene Expression Knockdown Using Small Inhibitory RNA-Loaded Microbubbles and Ultrasound.

Directory of Open Access Journals (Sweden)

Jonathan A Kopechek

Full Text Available RNA interference has potential therapeutic value for cardiac disease, but targeted delivery of interfering RNA is a challenge. Custom designed microbubbles, in conjunction with ultrasound, can deliver small inhibitory RNA to target tissues in vivo. The efficacy of cardiac RNA interference using a microbubble-ultrasound theranostic platform has not been demonstrated in vivo. Therefore, our objective was to test the hypothesis that custom designed microbubbles and ultrasound can mediate effective delivery of small inhibitory RNA to the heart. Microbubble and ultrasound mediated cardiac RNA interference was tested in transgenic mice displaying cardiac-restricted luciferase expression. Luciferase expression was assayed in select tissues of untreated mice (n = 14. Mice received intravenous infusion of cationic microbubbles bearing small inhibitory RNA directed against luciferase (n = 9 or control RNA (n = 8 during intermittent cardiac-directed ultrasound at mechanical index of 1.6. Simultaneous echocardiography in a separate group of mice (n = 3 confirmed microbubble destruction and replenishment during treatment. Three days post treatment, cardiac luciferase messenger RNA and protein levels were significantly lower in ultrasound-treated mice receiving microbubbles loaded with small inhibitory RNA directed against luciferase compared to mice receiving microbubbles bearing control RNA (23±7% and 33±7% of control mice, p<0.01 and p = 0.03, respectively. Passive cavitation detection focused on the heart confirmed that insonification resulted in inertial cavitation. In conclusion, small inhibitory RNA-loaded microbubbles and ultrasound directed at the heart significantly reduced the expression of a reporter gene. Ultrasound-targeted destruction of RNA-loaded microbubbles may be an effective image-guided strategy for therapeutic RNA interference in cardiac disease.

Rapidly Dissolving Microneedle Patches for Transdermal Iron Replenishment Therapy.

Science.gov (United States)

Maurya, Abhijeet; Nanjappa, Shivakumar H; Honnavar, Swati; Salwa, M; Murthy, S Narasimha

2018-02-17

The prevalence of iron deficiency anemia (IDA) is predominant in women and children especially in developing countries. The disorder affects cognitive functions and physical activity. Although oral iron supplementation and parenteral therapy remains the preferred choice of treatment, gastric side effects and risk of iron overload decreases adherence to therapy. Transdermal route is an established approach, which circumvents the side effects associated with conventional therapy. In this project, an attempt was made to investigate the use of rapidly dissolving microneedles loaded with ferric pyrophosphate (FPP) as a potential therapeutic approach for management of IDA. Microneedle array patches were made using the micromolding technique and tested in vitro using rat skin to check the duration required for dissolution/disappearance of needles. The ability of FPP-loaded microneedles to replenish iron was investigated in anemic rats. Rats were fed iron-deficient diet for 5 weeks to induce IDA following which microneedle treatment was initiated. Recovery of rats from anemic state was monitored by measuring hematological and biochemical parameters. Results from in vivo study displayed significant improvements in hemoglobin and serum iron levels after 2-week treatment with FPP-loaded microneedles. The study effectively demonstrated the potential of microneedle-mediated iron replenishment for treatment of IDA. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Thermoresponsive Hydrogels and Their Biomedical Applications: Special Insight into Their Applications in Textile Based Transdermal Therapy

Directory of Open Access Journals (Sweden)

Sudipta Chatterjee

2018-04-01

Full Text Available Various natural and synthetic polymers are capable of showing thermoresponsive properties and their hydrogels are finding a wide range of biomedical applications including drug delivery, tissue engineering and wound healing. Thermoresponsive hydrogels use temperature as external stimulus to show sol-gel transition and most of the thermoresponsive polymers can form hydrogels around body temperature. The availability of natural thermoresponsive polymers and multiple preparation methods of synthetic polymers, simple preparation method and high functionality of thermoresponsive hydrogels offer many advantages for developing drug delivery systems based on thermoresponsive hydrogels. In textile field applications of thermoresponsive hydrogels, textile based transdermal therapy is currently being applied using drug loaded thermoresponsive hydrogels. The current review focuses on the preparation, physico-chemical properties and various biomedical applications of thermoresponsive hydrogels based on natural and synthetic polymers and especially, their applications in developing functionalized textiles for transdermal therapies. Finally, future prospects of dual responsive (pH/temperature hydrogels made by these polymers for textile based transdermal treatments are mentioned in this review.

Formulation, characterization and clinical evaluation of propranolol hydrochloride gel for transdermal treatment of superficial infantile hemangioma.

Science.gov (United States)

Zhou, Wenhu; He, Shiying; Yang, Yijun; Jian, Dan; Chen, Xiang; Ding, Jinsong

2015-01-01

The objective of the present study is to formulate and characterize propranolol hydrochloride (PPL · HCl) gel, and to evaluate the efficacy of this formulation in transdermal treatment for superficial infantile hemangioma (IH). The transdermal PPL · HCl gel was prepared by a direct swelling method, which chose hydroxypropyl methylcellulose (HPMC) as the matrix and used terpenes plus alcohols as permeation enhancer. Permeation studies of PPL · HCl were carried out with modified Franz diffusion cells through piglet skin. Our results pointed to that among all studied permeation enhancers, farnesol plus isopropanol was the most effective combination (Q24, 6027.4 ± 563.1 μg/cm(2), ER, 6.8), which was significantly higher than that of control gel (p homemade PPL · HCl oral solution as a control. Clinical studies also confirmed the excellent therapeutic response and few side effects of the PPL · HCl gel. These results suggest that transdermal application of the PPL · HCl gel is an effective and safe formulation in treating superficial IH.

Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery

Directory of Open Access Journals (Sweden)

Naren Subbiah

2017-01-01

Full Text Available Phospholipid-based deformable nanovesicles (DNVs that have flexibility in shape offer an adaptable and facile method to encapsulate diverse classes of therapeutics and facilitate localized transdermal delivery while minimizing systemic exposure. Here we report the use of a microfluidic reactor for the synthesis of DNVs and show that alteration of input parameters such as flow speeds as well as molar and flow rate ratios increases entrapment efficiency of drugs and allows fine-tuning of DNV size, elasticity, and surface charge. To determine the ability of DNV-encapsulated drug to be delivered transdermally to a local site, we synthesized, characterized, and tested DNVs carrying the fluorescently labeled hydrophilic bisphosphonate drug AF-647 zoledronate (AF647-Zol. AF647-Zol DNVs were lyophilized, resuspended, and applied topically as a paste to the calvarial skin of mice. High-resolution fluorescent imaging and confocal microscopy revealed significant increase of encapsulated payload delivery to the target tissue—cranial bone—by DNVs as compared to nondeformable nanovesicles (NVs or aqueous drug solutions. Interestingly, NV delivery was not superior to aqueous drug solution. Our studies show that microfluidic reactor-synthesized DNVs can be produced in good yield, with high encapsulation efficiency, reproducibility, and stability after storage, and represent a useful vehicle for localized transdermal drug delivery.

Hydrogels containing redispersible spray-dried melatonin-loaded nanocapsules: a formulation for transdermal-controlled delivery

Science.gov (United States)

Hoffmeister, Cristiane RD; Durli, Taís L.; Schaffazick, Scheila R.; Raffin, Renata P.; Bender, Eduardo A.; Beck, Ruy CR; Pohlmann, Adriana R.; Guterres, Sílvia S.

2012-05-01

The aim of the present study was to develop a transdermal system for controlled delivery of melatonin combining three strategies: nanoencapsulation of melatonin, drying of melatonin-loaded nanocapsules, and incorporation of nanocapsules in a hydrophilic gel. Nanocapsules were prepared by interfacial deposition of the polymer and were spray-dried using water-soluble excipients. In vitro drug release profiles were evaluated by the dialysis bag method, and skin permeation studies were carried out using Franz cells with porcine skin as the membrane. The use of 10% ( w/ v) water-soluble excipients (lactose or maltodextrin) as spray-drying adjuvants furnished redispersible powders (redispersibility index approximately 1.0) suitable for incorporation into hydrogels. All formulations showed a better controlled in vitro release of melatonin compared with the melatonin solution. The best controlled release results were achieved with hydrogels prepared with dried nanocapsules (hydrogels > redispersed dried nanocapsules > nanocapsule suspension > melatonin solution). The skin permeation studies demonstrated a significant modulation of the transdermal melatonin permeation for hydrogels prepared with redispersible nanocapsules. In this way, the additive effect of the different approaches used in this study (nanoencapsulation, spray-drying, and preparation of semisolid dosage forms) allows not only the control of melatonin release, but also transdermal permeation.

Impact of various progestins with or without transdermal testosterone on gonadotropin levels for non-invasive hormonal male contraception: a randomized clinical trial.

Science.gov (United States)

Zitzmann, M; Rohayem, J; Raidt, J; Kliesch, S; Kumar, N; Sitruk-Ware, R; Nieschlag, E

2017-05-01

Although several progestins have been tested for hormonal male contraception, the effects of dosage and nature of various progestins on gonadotropin suppression combined with and without additional testosterone has not been performed in a comparative trial. The aim of this study was to evaluate the differential impact of four oral or transdermal progestins on the suppression of gonadotropins in healthy men: oral: cyproterone acetate (CPA), levonorgestrel (LNG), norethisterone acetate (NETA), and transdermal: Nestorone ® (NES), all in combination with transdermal testosterone (T). Randomized clinical trial testing was performed with four progestins at two doses each. After a 2-week progestin-only treatment, transdermal T was added for further 4 weeks and was followed by a 3-week recovery period. Progestin-dose per day: CPA 10 mg/20 mg, NES 2 mg/3 mg/dose e.g. 200/300 μg/day absorbed, NETA 5 mg/10 mg, LNG 120 μg/240 μg. From an andrology outpatient clinic, 56 healthy men aged 18-50 years, with body mass index ≤33 kg × m -2 were included in the study. Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied. Secondary outcome measure included were serum testosterone concentrations, sperm concentrations, and safety parameters. Intergroup comparisons demonstrated that CPA and LNG had the strongest effect on LH/FSH suppression. Nevertheless, every substance showed significant inhibitory effects on gonadotropin secretion, especially in combination with transdermal T. A decrease in hematocrit and insulin sensitivity as well as cholesterol subfractions and triglycerides was uniformly seen for every group. The combination of oral or transdermal progestins with a transdermal testosterone preparation is able to suppress gonadotropins. Further dose titration studies with sperm suppression as an end-point should be conducted to determine the lowest effective dose for hormonal male contraception. © 2017 American

Skin temperature increase mediated by wearable, long duration, low-intensity therapeutic ultrasound

Science.gov (United States)

Langer, Matthew D.; Huang, Wenyi; Ghanem, Angi; Guo, Yuan; Lewis, George K.

2017-03-01

One of the safety concerns with the delivery of therapeutic ultrasound is overheating of the transducer-skin interface due to poor or improper coupling. The objective of this research was to define a model that could be used to calculate the heating in the skin as a result of a novel, wearable long-duration ultrasound device. This model was used to determine that the maximum heating in the skin remained below the minimum threshold necessary to cause thermal injury over multiple hours of use. In addition to this model data, a human clinical study used wire thermocouples on the skin surface to measure heating characteristics during treatment with the sustained ultrasound system. Parametric analysis of the model determined that the maximum temperature increase is at the surface of the skin ranged from 40-41.8° C when perfusion was taken into account. The clinical data agreed well with the model predictions. The average steady state temperature observed across all 44 subjects was 40°C. The maximum temperature observed was less than 44° C, which is clinically safe for over 5 hours of human skin contact. The resultant clinical temperature data paired well with the model data suggesting the model can be used for future transducer and ultrasound system design simulation. As a result, the device was validated for thermal safety for typical users and use conditions.

Trans-Stent B-Mode Ultrasound and Passive Cavitation Imaging.

Science.gov (United States)

Haworth, Kevin J; Raymond, Jason L; Radhakrishnan, Kirthi; Moody, Melanie R; Huang, Shao-Ling; Peng, Tao; Shekhar, Himanshu; Klegerman, Melvin E; Kim, Hyunggun; McPherson, David D; Holland, Christy K

2016-02-01

Angioplasty and stenting of a stenosed artery enable acute restoration of blood flow. However, restenosis or a lack of re-endothelization can subsequently occur depending on the stent type. Cavitation-mediated drug delivery is a potential therapy for these conditions, but requires that particular types of cavitation be induced by ultrasound insonation. Because of the heterogeneity of tissue and stochastic nature of cavitation, feedback mechanisms are needed to determine whether the sustained bubble activity is induced. The objective of this study was to determine the feasibility of passive cavitation imaging through a metal stent in a flow phantom and an animal model. In this study, an endovascular stent was deployed in a flow phantom and in porcine femoral arteries. Fluorophore-labeled echogenic liposomes, a theragnostic ultrasound contrast agent, were injected proximal to the stent. Cavitation images were obtained by passively recording and beamforming the acoustic emissions from echogenic liposomes insonified with a low-frequency (500 kHz) transducer. In vitro experiments revealed that the signal-to-noise ratio for detecting stable cavitation activity through the stent was greater than 8 dB. The stent did not significantly reduce the signal-to-noise ratio. Trans-stent cavitation activity was also detected in vivo via passive cavitation imaging when echogenic liposomes were insonified by the 500-kHz transducer. When stable cavitation was detected, delivery of the fluorophore into the arterial wall was observed. Increased echogenicity within the stent was also observed when echogenic liposomes were administered. Thus, both B-mode ultrasound imaging and cavitation imaging are feasible in the presence of an endovascular stent in vivo. Demonstration of this capability supports future studies to monitor restenosis with contrast-enhanced ultrasound and pursue image-guided ultrasound-mediated drug delivery to inhibit restenosis. Copyright © 2016 World Federation for

Amphiphilic poly{[α-maleic anhydride-ω-methoxypoly(ethylene glycol]-co-(ethyl cyanoacrylate} graft copolymer nanoparticles as carriers for transdermal drug delivery

Directory of Open Access Journals (Sweden)

Jinfeng Xing

2009-10-01

Full Text Available Jinfeng Xing, Liandong Deng, Jun Li, Anjie DongDepartment of Polymer Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, People’s Republic of ChinaAbstract: In this study, the transdermal drug delivery properties of D,L-tetrahydropalmatine (THP-loaded amphiphilic poly{[α-maleic anhydride-ω-methoxy-poly(ethylene glycol]-co-(ethyl cyanoacrylate} (PEGECA graft copolymer nanoparticles (PEGECAT NPs were evaluated by skin penetration experiments in vitro. The transdermal permeation experiments in vitro were carried out in Franz diffusion cells using THP-loaded PEGECAT NPs as the donor system. Transmission electron microscopy and Fourier transform infrared spectroscopy were used to characterize the receptor fluid. The results indicate that the THP-loaded PEGECAT NPs are able to penetrate the rat skin. Fluorescent microscopy measurements demonstrate that THP-loaded PEGECAT NPs can penetrate the skin not only via appendage routes but also via epidermal routes. This nanotechnology has potential application in transdermal drug delivery. Keywords: poly{[α-maleic anhydride-ω-methoxy-poly(ethylene glycol]-co-(ethyl cyanoacrylate}, nanoparticles, transdermal drug delivery, D,L-tetrahydropalmatine

Efficacy and safety of a transdermal contraceptive system.

Science.gov (United States)

Smallwood, G H; Meador, M L; Lenihan, J P; Shangold, G A; Fisher, A C; Creasy, G W

2001-11-01

To evaluate the efficacy, cycle control, compliance, and safety of a transdermal contraceptive system that delivers norelgestromin 150 microg and ethinyl estradiol 20 microg daily. In this open-label, 73-center study, 1672 healthy, ovulatory, sexually active women received ORTHO EVRA/EVRA for six (n = 1171) or 13 cycles (n = 501). The treatment regimen for each cycle was three consecutive 7-day patches (21 days) followed by 1 patch-free week. The overall and method-failure probabilities of pregnancy through 13 cycles were 0.7% and 0.4%, respectively. The incidence of breakthrough bleeding was low throughout the study. Perfect compliance (21 consecutive days of dosing, followed by a 7-day drug-free interval; no patch could be worn for more than 7 days) was achieved in 90% of subject cycles; only 1.9% of patches detached completely. Adverse events were typical of hormonal contraception, and most were mild-to-moderate in severity and not treatment limiting. The most common adverse events resulting in discontinuation were application site reactions (1.9%), nausea (1.8%), emotional lability (1.5%), headache (1.1%), and breast discomfort (1.0%). The transdermal contraceptive patch provides effective contraception and cycle control, and is well tolerated. The weekly change schedule for the contraceptive patch is associated with excellent compliance and wearability characteristics.

Preparation and the in vitro evaluation of nanoemulsion system for the transdermal delivery of granisetron hydrochloride.

Science.gov (United States)

Zheng, Wen-wu; Zhao, Ling; Wei, Yu-meng; Ye, Yun; Xiao, Shun-han

2010-08-01

The objective of this study was to develop and evaluate nanoemulsion system for transdermal delivery of granisetron hydrochloride. Pseudo-ternary phase diagram was constructed to ascertain the concentration range of components of nanoemulsion composed of isopropyl myristate (IPM) as an oil phase, tween 85 as surfactant, ethanol as cosurfactant, water as aqueous phase. The effects of the content of IPM as an oil phase and n-methyl pyrrolidone (NMP) as transdermal enhancer on rat skin permeation of granisetron hydrochloride nanoemulsion were studied in vitro. The results showed that the mean particle size of nanoemulsion ranged from 50.4+/-1.5 to 82.4+/-0.9 nm with homogeneous size distribution. The resulted optimum formulation composed of 2.5% granisetron hydrochloride, 4% IPM, 40% tween 85/ethanol (1 : 1) and 10% NMP showed that the skin permeation rate was the highest (85.39+/-2.90 microg/cm(2)/h) and enhancement of drug permeability was 4.1-fold for transdermal delivery of granisetron hydrochloridein comparison with the control group (20% of tween 85 and 20% of ethanol micelle solution containing 2.5% of granisetron hydrochloride without IPM), and cumulative permeation amount was the highest (891.8+/-2.86 microg/cm(2)) with the shortest lag time (0.11+/-0.02 h) and was stable for at least 12 months. Therefore, the nanoemulsion system developed in this study offers a promising vehicle for the transdermal delivery system of granisetron hydrochloride, which may be as effective as oral or intravenous dosage forms and avoid some difficulties associated with these dosage forms.

In vitro study of the effects of ultrasound-mediated glycerol on optical attenuation of human normal and cancerous esophageal tissues with optical coherence tomography

International Nuclear Information System (INIS)

Zhang, Y Q; Wei, H J; Guo, Z Y; Gu, H M; Guo, X; Zhu, Z G; Yang, H Q; Xie, S S

2013-01-01

Previous studies from our group have demonstrated that glucose solution can induce optical clearing enhancement of esophageal tissues with optical coherence tomography (OCT). The aims of this study were to evaluate the optical clearing effects of ultrasound-mediated optical clearing agents (OCAs) and to find more effective methods to distinguish human normal esophageal tissues (NE) and cancerous esophageal tissues (CE). Here we used the OCT technique to investigate the optical attenuation of NE and CE in vitro after treatment with 30% glycerol alone and glycerol combined with ultrasound, respectively. Experimental results showed that the averaged attenuation coefficient of CE was significantly larger than that of NE. The maximal decreases of averaged attenuation coefficients of NE and CE were approximately 48.7% and 36.2% after treatment with 30% glycerol alone, and they were significantly lower than those treated with 30% glycerol and ultrasound (57.5% in NE and 44.8% in CE). Moreover, after treatment with 30% glycerol alone, the averaged attenuation coefficients of NE and CE reached their minima in about 80 min and 65 min, respectively. The times were much shorter in NE and CE after treatment with glycerol with ultrasound, being about 62 min and 50 min, respectively. The results suggest that there is a significant difference in the optical properties of NE and CE, and that OCT with an ultrasound–OCAs combination has the ability to distinguish CE from NE. (paper)

Tolterodine Tartrate Proniosomal Gel Transdermal Delivery for Overactive Bladder

Directory of Open Access Journals (Sweden)

Rajan Rajabalaya

2016-08-01

Full Text Available The goal of this study was to formulate and evaluate side effects of transdermal delivery of proniosomal gel compared to oral tolterodine tartrate (TT for the treatment of overactive bladder (OAB. Proniosomal gels are surfactants, lipids and soy lecithin, prepared by coacervation phase separation. Formulations were analyzed for drug entrapment efficiency (EE, vesicle size, surface morphology, attenuated total reflectance Fourier transform infrared (ATR-FTIR spectroscopy, in vitro skin permeation, and in vivo effects. The EE was 44.87%–91.68% and vesicle size was 253–845 nm for Span formulations and morphology showed a loose structure. The stability and skin irritancy test were also carried out for the optimized formulations. Span formulations with cholesterol-containing formulation S1 and glyceryl distearate as well as lecithin containing S3 formulation showed higher cumulative percent of permeation such as 42% and 35%, respectively. In the in vivo salivary secretion model, S1 proniosomal gel had faster recovery, less cholinergic side effect on the salivary gland compared with that of oral TT. Histologically, bladder of rats treated with the proniosomal gel formulation S1 showed morphological improvements greater than those treated with S3. This study demonstrates the potential of proniosomal vesicles for transdermal delivery of TT to treat OAB.

Efficient Transdermal Delivery of Benfotiamine in an Animal Model

Directory of Open Access Journals (Sweden)

Gyula Varadi

2015-01-01

Full Text Available We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake.  Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-epithelial layers.  In this proof of concept study in guinea pigs, we found that a single topical application of either a solubilized form of benfotiamine (15 mg or a microcrystalline suspension form (25 mg resulted in considerable increases of the dephosphorylated benfotiamine (S-benzoylthiamine in the skin tissue as well as in significant increases in the thiamine and thiamine phosphate pools compared to control animals.  The presence of a ~8000x increase in thiamine and increases in its phosphorylated derivatives in the epidermis and dermis tissue of the test animals gives a strong indication that the topical treatment with benfotiamine works very well for the desired outcome of producing an intracellular increase of the activating cofactor pool for transketolase enzyme, which is implicated in the pathophysiology of diabetic neuropathy.

Transesterification of used vegetable oil catalyzed by barium oxide under simultaneous microwave and ultrasound irradiations

International Nuclear Information System (INIS)

Martinez-Guerra, Edith; Gude, Veera Gnaneswar

2014-01-01

Graphical abstract: Transesterification reaction mediated by simultaneous microwave and ultrasound irradiations with barium oxide (BaO) heterogeneous catalyst. - Highlights: • Synergistic effect of simultaneous microwave/ultrasound irradiations was evaluated. • Yields were higher for the MW/US reactions compared to MW or US individually. • BaO catalyzed MW/US transesterification reaction is more environmental-friendly. • BaO catalyzed MW/US transesterification reaction provides better biodiesel yields. • Optimum power density must be identified for energy-efficient biodiesel production. - Abstract: This study presents a novel application of simultaneous microwave and ultrasound (MW/US) irradiations on transesterification of used vegetable oil catalyzed by barium oxide, heterogeneous catalyst. Experiments were conducted to study the optimum process conditions, synergistic effect of microwave and ultrasound irradiations and the effect of power density. From the process parametric optimization study, the following conditions were determined as optimum: 6:1 methanol to oil ratio, 0.75% barium oxide catalyst by wt.%, and 2 min of reaction time at a combined power output rate of 200 W (100/100 MW/US). The biodiesel yields were higher for the simultaneous MW/US mediated reactions (∼93.5%) when compared to MW (91%) and US (83.5%) irradiations individually. Additionally, the effect of power density and a discussion on the synergistic effect of the microwave and ultrasound mediated reactions were presented. A power density of 7.6 W/mL appears to be effective for MW, and MW/US irradiated reactions (94.4% and 94.7% biodiesel yields respectively), while a power density of 5.1 W/mL was appropriate for ultrasound irradiation (93.5%). This study concludes that the combined microwave and ultrasound irradiations result in a synergistic effect that reduces the heterogeneity of the transesterification reaction catalyzed by heterogeneous catalysts to enhance the biodiesel

Development of domperidone bilayered matrix type transdermal patches: physicochemical, in vitro and ex vivo characterization

Directory of Open Access Journals (Sweden)

S.K Madishetti

2010-09-01

Full Text Available "nBackground and the purpose of the study: Domperidone (DOM is a dopamine- receptor (D2 antagonist, which is widely used in the treatment of motion-sickness. The pharmacokinetic parameters make DOM a suitable candidate for transdermal delivery. The purpose of the present investigation was to develop transdermal delivery systems for DOM and to evaluate their physicochemical characteristics, in vitro release an ex vivo permeation through rat abdominal skin and their mechanical properties. "nMethods: Bilayered matrix type transdermal drug delivery systems (TDDS of DOM were prepared by film casting technique using hydroxypropyl methyl cellulose as primary and Eudragit RL 100 as secondary layers. Brij-35 was incorporated as a solubilizer, d-limonene and propylene glycol were employed as permeation enhancer and plasticizer respectively. The prepared TDDS were extensively evaluated for in vitro release, moisture absorption, moisture content, water vapor transmission, ex vivo permeation through rat abdominal skin, mechanical properties and stability studies. The physicochemical interaction between DOM and polymers were investigated by Differential Scanning Calorimetry (DSC and Fourier Transform Infrared Spectroscopy (FTIR. "nResults: All the formulations exhibited satisfactory physicochemical and mechanical characteristics. The optimized formulation F6 showed maximum cumulative percentage of drug release (90.7%, permeation (6806.64 μg in 24 hrs, flux (86.02 μg /hr/cm2 and permeation coefficient of 0.86x10-2 cm/hr. Values of tensile strength (4.34 kg/mm2 and elastic modulus (5.89 kg/cm2 revealed that formulation F6 was strong but not brittle. DSC and FTIR studies showed no evidence of interaction between the drug and polymers. A shelf life of 2 years is predicted for the TDDS. Conclusions: Domperidone bilayered matrix type transdermal therapeutic systems could be prepared with the required flux and suitable mechanical properties.

Recent developments in skin mimic systems to predict transdermal permeation.

Science.gov (United States)

Waters, Laura J

2015-01-01

In recent years there has been a drive to create experimental techniques that can facilitate the accurate and precise prediction of transdermal permeation without the use of in vivo studies. This review considers why permeation data is essential, provides a brief summary as to how skin acts as a natural barrier to permeation and discusses why in vivo studies are undesirable. This is followed by an in-depth discussion on the extensive range of alternative methods that have been developed in recent years. All of the major 'skin mimic systems' are considered including: in vitro models using synthetic membranes, mathematical models including quantitative structure-permeability relationships (QSPRs), human skin equivalents and chromatographic based methods. All of these model based systems are ideally trying to achieve the same end-point, namely a reliable in vitro-in vivo correlation, i.e. matching non-in vivo obtained data with that from human clinical trials. It is only by achieving this aim, that any new method of obtaining permeation data can be acknowledged as a potential replacement for animal studies, for the determination of transdermal permeation. In this review, the relevance and potential applicability of the various models systems will also be discussed.

The dynamic behavior of microbubbles during long ultrasound tone-burst excitation: mechanistic insights into ultrasound-microbubble mediated therapeutics using high-speed imaging and cavitation detection

Science.gov (United States)

Pacella, John J.; Villanueva, Flordeliza S.

2015-01-01

Ultrasound (US)-microbubble (MB) mediated therapies have been shown to restore perfusion and enhance drug/gene delivery. Due to the presumption that MBs do not persist during long US exposure under high acoustic pressures, most schemes utilize short US pulses when a high US pressure is employed. However, we recently observed an enhanced thrombolytic effect using long US pulses at high acoustic pressures. Therefore we explored the fate of MBs during long tone-burst exposures (5 ms) at various acoustic pressures and MB concentrations via direct high-speed optical observation and passive cavitation detection. MBs first underwent stable or inertial cavitation depending on the acoustic pressure, and then formed gas-filled clusters that continued to oscillate, break up, and form new clusters. Cavitation detection confirmed continued, albeit diminishing acoustic activity throughout the 5-ms US excitation. These data suggest that persisting cavitation activity during long tone-bursts may confer additional therapeutic effects. PMID:26603628

Lipid Nanocapsule-Based Gels for Enhancement of Transdermal Delivery of Ketorolac Tromethamine

Directory of Open Access Journals (Sweden)

Jaleh Varshosaz

2011-01-01

Full Text Available Previous reports show ineffective transdermal delivery of ketorolac by nanostructured lipid carriers (NLCs. The aim of the present work was enhancement of transdermal delivery of ketorolac by another colloidal carriers, lipid nanocapsules (LNCs. LNCs were prepared by emulsification with phase transition method and mixed in a Carbomer 934P gel base with oleic acid or propylene glycol as penetration enhancers. Permeation studies were performed by Franz diffusion cell using excised rat abdominal skin. Aerosil-induced rat paw edema model was used to investigate the in vivo performance. LNCs containing polyethylene glycol hydroxyl stearate, lecithin in Labrafac as the oily phase, and dilution of the primary emulsion with 3.5-fold volume of cold water produced the optimized nanoparticles. The 1% Carbomer gel base containing 10% oleic acid loaded with nanoparticles enhanced and prolonged the anti-inflammatory effects of this drug to more than 12 h in Aerosil-induced rat paw edema model.

Response to intravenous fentanyl infusion predicts subsequent response to transdermal fentanyl.

Science.gov (United States)

Hayashi, Norihito; Kanai, Akifumi; Suzuki, Asaha; Nagahara, Yuki; Okamoto, Hirotsugu

2016-04-01

Prediction of the response to transdermal fentanyl (FENtd) before its use for chronic pain is desirable. We tested the hypothesis that the response to intravenous fentanyl infusion (FENiv) can predict the response to FENtd, including the analgesic and adverse effects. The study subjects were 70 consecutive patients with chronic pain. The response to fentanyl at 0.1 mg diluted in 50 ml of physiological saline and infused over 30 min was tested. This was followed by treatment with FENtd (Durotep MT patch 2.1 mg) at a dose of 12.5 µg/h for 2 weeks. Pain intensity before and after FENiv and 2 weeks after FENtd, and the response to treatment, were assessed by the numerical rating scale (NRS), clinical global impression-improvement scale (CGI-I), satisfaction scale (SS), and adverse effects. The NRS score decreased significantly from 7 (4-9) [median (range)] at baseline to 3 (0-8) after FENiv (p 0.04, each). The analgesic and side effects after intravenous fentanyl infusion can be used to predict the response to short-term transdermal treatment with fentanyl.

Enhanced delivery of hydrophilic peptides in vitro by transdermal microneedle pretreatment.

Science.gov (United States)

Zhang, Suohui; Qiu, Yuqin; Gao, Yunhua

2014-02-01

The aims of this study were to investigate the utility of solid microneedle arrays (150 µm in length) in enhancing transdermal delivery of peptides and to examine the relationship between peptide permeation rates and D2O flux. Four model peptides were used (Gly-Gln-Pro-Arg [tetrapeptide-3, 456.6 Da], Val-Gly-Val-Ala-Pro-Gly [hexapeptide, 498.6 Da], AC-Glu-Glu-Met-Gln-Arg-Arg-NH2 [acetyl hexapeptide-3, 889 Da] and Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2 [oxytocin, 1007.2 Da]). The influence of microneedle pretreatment on skin permeation was evaluated using porcine ear skin with Franze diffusion cell. Peptide permeation across the skin was significantly enhanced by microneedle pretreatment, and permeation rates were dependent on peptide molecular weights. A positive correlation between D2O flux and acetyl hexapeptide-3 clearances suggests that convective solvent flow contributes to the enhanced transdermal peptide delivery. It is concluded that solid microneedle arrays are effective devices to enhance skin delivery of peptides.

Enhanced delivery of hydrophilic peptides in vitro by transdermal microneedle pretreatment

Directory of Open Access Journals (Sweden)

Suohui Zhang

2014-02-01

Full Text Available The aims of this study were to investigate the utility of solid microneedle arrays (150 µm in length in enhancing transdermal delivery of peptides and to examine the relationship between peptide permeation rates and D2O flux. Four model peptides were used (Gly–Gln–Pro–Arg [tetrapeptide-3, 456.6 Da], Val–Gly–Val–Ala–Pro–Gly [hexapeptide, 498.6 Da], AC–Glu–Glu–Met–Gln–Arg–Arg–NH2 [acetyl hexapeptide-3, 889 Da] and Cys–Tyr–Ile–Gln–Asn–Cys–Pro–Leu–Gly–NH2 [oxytocin, 1007.2 Da]. The influence of microneedle pretreatment on skin permeation was evaluated using porcine ear skin with Franze diffusion cell. Peptide permeation across the skin was significantly enhanced by microneedle pretreatment, and permeation rates were dependent on peptide molecular weights. A positive correlation between D2O flux and acetyl hexapeptide-3 clearances suggests that convective solvent flow contributes to the enhanced transdermal peptide delivery. It is concluded that solid microneedle arrays are effective devices to enhance skin delivery of peptides.

Microemulsion for simultaneous transdermal delivery of benzocaine and indomethacin: in vitro and in vivo evaluation.

Science.gov (United States)

El Maghraby, Gamal M; Arafa, Mona F; Osman, Mohamed A

2014-12-01

This study investigated simultaneous transdermal delivery of indomethacin and benzocaine from microemulsion. Eucalyptus oil based microemulsion was used with Tween 80 and ethanol being employed as surfactant and cosurfactant, respectively. A microemulsion formulation comprising eucalyptus oil, polyoxyethylene sorbitan momooleate (Tween 80), ethanol and water (20:30:30:20) was selected. Indomethacin (1% w/w) and benzocaine (20% w/w) were incorporated separately or combined into this formulation before in vitro and in vivo evaluation. Application of indomethacin microemulsion enhanced the transdermal flux and reduced the lag time compared to saturated aqueous control. The same trend was evident for benzocaine microemulsion. Simultaneous application of the two drugs in microemulsion provided similar enhancement pattern. The in vivo evaluation employed the pinprick method and revealed rapid anesthesia after application of benzocaine microemulsion with the onset being 10 min and the action lasting for 50 min. For indomethacin microemulsion, the analgesic effect was recorded after 34.5 min and lasted for 70.5 min. Simultaneous application of benzocaine and indomethacin provided synergistic effect. The onset of action was achieved after 10 min and lasted for 95 min. The study highlighted the potential of microemulsion formulation in simultaneous transdermal delivery of two drugs.

Once-daily transdermal rivastigmine in the treatment of Alzheimer’s disease

Directory of Open Access Journals (Sweden)

Andreas Wentrup

2008-11-01

Full Text Available Andreas Wentrup, Wolfgang H Oertel, Richard DodelDepartment of Neurology, Philipps-University Marburg, GermanyAbstract: During the past decade, transdermal delivery systems (TDS have become increasingly important for treating neurologic and psychiatric disorders. The rivastigmine patch was the first patch to be approved to treat Alzheimer’s disease (AD. The 9.5 mg/24 h patch has equal efficacy to the capsules and reduces gastrointestinal adverse events, such as nausea and vomiting, by two-thirds. This treatment is well tolerated by patients because drug delivery is even and continuous, reducing fluctuation in drug plasma level, and attenuating the development of centrally mediated cholinergic side effects. Furthermore, once-a-day application of the patch enables an easy treatment schedule, ease of handling, infrequent skin irritations, and a patient- and caregiver-friendly mode of administration. Improved compliance with a subsequent drug administration may contribute to better clinical efficacy, reduce caregiver burden, result in a slower rate of institutionalization, and lead to a decrease in healthcare and medical costs. Because of these advantages, the rivastigmine patch has enabled great progress in the treatment of AD, and represents an excellent alternative to the orally administered cholinesterase inhibitors.Keywords: Alzheimer’s disease, rivastigmine, patch, dementia

Local transdermal therapy to the breast for breast cancer prevention and DCIS therapy: preclinical and clinical evaluation.

Science.gov (United States)

Lee, Oukseub; Ivancic, David; Allu, Subhashini; Shidfar, Ali; Kenney, Kara; Helenowski, Irene; Sullivan, Megan E; Muzzio, Miguel; Scholtens, Denise; Chatterton, Robert T; Bethke, Kevin P; Hansen, Nora M; Khan, Seema A

2015-12-01

Women at high risk of breast cancer and those with carcinoma in situ need non-toxic, well-tolerated preventive interventions. One promising approach is drug delivery through the breast skin (local transdermal therapy, LTT). Our goal was to test novel drugs for LTT, to establish that LTT is applicable to non-steroidal drugs. Athymic nude rats were treated with oral tamoxifen, transdermal 4-hydroxytamoxifen (4-OHT) or endoxifen gel applied daily to the axillary mammary gland for 6 weeks (Study 1). Study 2 was identical to Study 1, testing transdermal telapristone acetate (telapristone) gel versus subcutaneous implant. At euthanasia, mammary glands and blood were collected. In Study 3, consenting women requiring mastectomy were randomized to diclofenac patch applied to the abdomen or the breast for 3 days preoperatively. At surgery, eight tissue samples per breast were collected from predetermined locations, along with venous blood. Drug concentrations were measured using liquid chromatography-tandem mass spectroscopy. Mammary tissue concentrations of 4-OHT, endoxifen, and telapristone were significantly higher in the axillary glands of the gel-treated animals, compared to inguinal glands or to systemically treated animals. Plasma concentrations were similar in gel and systemically treated animals. The clinical trial showed significantly higher mammary concentrations when diclofenac was applied to the breast skin versus the abdominal skin, but concentrations were variable. These results demonstrate that lipophilic drugs can be developed for LTT; although the nude rat is suitable for testing drug permeability, delivery is systemic. In human, however, transdermal application to the breast skin provides local delivery.

Controlled release of optimized electroporation enhances the transdermal efficiency of sinomenine hydrochloride for treating arthritis in vitro and in clinic

Science.gov (United States)

Feng, Shun; Zhu, Lijun; Huang, Zhisheng; Wang, Haojia; Li, Hong; Zhou, Hua; Lu, Linlin; Wang, Ying; Liu, Zhongqiu; Liu, Liang

2017-01-01

Sinomenine hydrochloride (SH) is an ideal drug for the treatment of rheumatoid arthritis and osteoarthritis. However, high plasma concentration of systemically administered SH can release histamine, which can cause rash and gastrointestinal side effects. Topical delivery can increase SH concentration in the synovial fluid without high plasma level, thus minimizing systemic side effects. However, passive diffusion of SH was found to be inefficient because of the presence of the stratum corneum layer. Therefore, an effective method is required to compensate for the low efficiency of SH passive diffusion. In this study, transdermal experiments in vitro and clinical tests were utilized to explore the optimized parameters for electroporation of topical delivery for SH. Fluorescence experiment and hematoxylin and eosin staining analysis were performed to reveal the mechanism by which electroporation promoted permeation. In vitro, optimized electroporation parameters were 3 KHz, exponential waveform, and intensity 10. Using these parameters, transdermal permeation of SH was increased by 1.9–10.1 fold in mice skin and by 1.6–47.1 fold in miniature pig skin compared with passive diffusion. After the electroporation stimulation, the intercellular intervals and epidermal cracks in the skin increased. In clinical tests, SH concentration in synovial fluid was 20.84 ng/mL after treatment with electroporation. Therefore, electroporation with optimized parameters could significantly enhance transdermal permeation of SH. The mechanism by which electroporation promoted permeation was that the electronic pulses made the skin structure looser. To summarize, electroporation may be an effective complementary method for transdermal permeation of SH. The controlled release of electroporation may be a promising clinical method for transdermal drug administration. PMID:28670109

The Role of Acoustic Cavitation in Ultrasound-triggered Drug Release from Echogenic Liposomes

Science.gov (United States)

Kopechek, Jonathan A.

Cardiovascular disease (CVD) is the leading cause of death in the United States and globally. CVD-related mortality, including coronary heart disease, heart failure, or stroke, generally occurs due to atherosclerosis, a condition in which plaques build up within arterial walls, potentially causing blockage or rupture. Targeted therapies are needed to achieve more effective treatments. Echogenic liposomes (ELIP), which consist of a lipid membrane surrounding an aqueous core, have been developed to encapsulate a therapeutic agent and/or gas bubbles for targeted delivery and ultrasound image enhancement. Under certain conditions ultrasound can cause nonlinear bubble growth and collapse, known as "cavitation." Cavitation activity has been associated with enhanced drug delivery across cellular membranes. However, the mechanisms of ultrasound-mediated drug release from ELIP have not been previously investigated. Thus, the objective of this dissertation is to elucidate the role of acoustic cavitation in ultrasound-mediated drug release from ELIP. To determine the acoustic and physical properties of ELIP, the frequency-dependent attenuation and backscatter coefficients were measured between 3 and 30 MHz. The results were compared to a theoretical model by measuring the ELIP size distribution in order to determine properties of the lipid membrane. It was found that ELIP have a broad size distribution and can provide enhanced ultrasound image contrast across a broad range of clinically-relevant frequencies. Calcein, a hydrophilic fluorescent dye, and papaverine, a lipophilic vasodilator, were separately encapsulated in ELIP and exposed to color Doppler ultrasound pulses from a clinical diagnostic ultrasound scanner in a flow system. Spectrophotometric techniques (fluorescence and absorbance measurements) were used to detect calcein or papaverine release. As a positive control, Triton X-100 (a non-ionic detergent) was added to ELIP samples not exposed to ultrasound in order

Conductive polymer nanotube patch for fast and controlled in vivo transdermal drug delivery

Science.gov (United States)

Nguyen, Thao M.

Transdermal drug delivery has created new applications for existing therapies and offered an alternative to the traditional oral route where drugs can prematurely metabolize in the liver causing adverse side effects. Opening the transdermal delivery route to large hydrophilic drugs is one of the greatest challenges due to the hydrophobicity of the skin. However, the ability to deliver hydrophilic drugs using a transdermal patch would provide a solution to problems of other delivery methods for hydrophilic drugs. The switching of conductive polymers (CP) between redox states cause simultaneous changes in the polymer charge, conductivity, and volume—properties that can all be exploited in the biomedical field of controlled drug delivery. Using the template synthesis method, poly(3,4-ethylenedioxythiophene (PEDOT) nanotubes were synthesized electrochemically and a transdermal drug delivery patch was successfully designed and developed. In vitro and in vivo uptake and release of hydrophilic drugs were investigated. The relationship between the strength of the applied potential and rate of drug release were also investigated. Results revealed that the strength of the applied potential is proportional to the rate of drug release; therefore one can control the rate of drug release by controlling the applied potential. The in vitro studies focused on the kinetics of the drug delivery system. It was determined that the drug released mainly followed zero-order kinetics. In addition, it was determined that applying a releasing potential to the transdermal drug delivery system lead to a higher release rate constant (up to 7 times greater) over an extended period of time (˜24h). In addition, over 24 hours, an average of 80% more model drug molecules were released with an applied potential than without. The in vivo study showed that the drug delivery system was capable of delivering model hydrophilic drugs molecules through the dermis layer of the skin within 30 minutes

Simultaneous, noninvasive, and transdermal extraction of urea and homocysteine by reverse iontophoresis

Directory of Open Access Journals (Sweden)

et al

2011-02-01

Full Text Available Congo Tak-Shing Ching1,2,3, Tzong-Ru Chou1, Tai-Ping Sun1,2, Shiow-Yuan Huang3, Hsiu-Li Shieh21Graduate Institute of Biomedicine and Biomedical Technology; 2Department of Electrical Engineering, National Chi Nan University, Nantou, Taiwan; 3Department of Photonics and Communication Engineering, Asia University, Taichung, Taiwan, Republic of ChinaBackground: Cardiovascular and kidney diseases are a global public health problem and impose a huge economic burden on health care services. Homocysteine, an amino acid, is associated with coronary heart disease, while urea is a harmful metabolic substance which can be used to reflect kidney function. Monitoring of these two substances is therefore very important. This in vitro study aimed to determine whether homocysteine is extractable transdermally and noninvasively, and whether homocysteine and urea can be extracted simultaneously by reverse iontophoresis.Methods: A diffusion cell incorporated with porcine skin was used for all experiments with the application of a direct current (dc and four different symmetrical biphasic direct currents (SBdc for 12 minutes via Ag/AgCl electrodes. The dc and the SBdc had a current density of 0.3 mA/cm2.Results: The SBdc has four different phase durations of 15 sec, 30 sec, 60 sec, and 180 sec. It was found that homocysteine can be transdermally extracted by reverse iontophoresis. Simultaneous extraction of homocysteine and urea by reverse iontophoresis is also possible.Conclusion: These results suggest that extraction of homocysteine and urea by SBdc are phase duration-dependent, and the optimum mode for simultaneous homocysteine and urea extraction is the SBdc with the phase duration of 60 sec.Keywords: reverse iontophoresis, homocysteine, urea, monitoring, noninvasive, transdermal

Optimization of transdermal delivery using magainin pore-forming peptide

OpenAIRE

Kim, Yeu-Chun; Ludovice, Peter J.; Prausnitz, Mark R.

2008-01-01

The skin's outer layer of stratum corneum, which is a thin tissue containing multilamellar lipid bilayers, is the main barrier to drug delivery to the skin. To increase skin permeability, our previous work has shown large enhancement of transdermal permeation using a pore-forming peptide, magainin, which was formulated with N-lauroyl sarcosine (NLS) in 50% ethanol-in-PBS. Mechanistic analysis suggested that magainin and NLS can increase skin permeability by disrupting stratum corneum lipid st...

Transdermic absorption of Melagenina II

International Nuclear Information System (INIS)

Hernandez Gonzalez, I.; Martinez Lopez, B.; Ruiz Pena, M.; Caso Pena, R.

1997-01-01

The transdermic absorption of Melagenina II (MII) was evaluated. MII was a labelled with 125I by the yodogen method and purified by column chromatography with Sephadex LH-20 in ethanol: water (7:3). In vitro absorption of ( 125I ) - MII thought human skin was carried out in Keshary-Chien modified diffusion cells. Tape stripping method was applied after 24 hours to evaluate the accumulated activity in dermis and epidermis. In vivo assays were performed in Sprague Dawley rats to analyze absorption of MII until 24 hours after a single application and for five days a low penetrability of the drug while in vivo there were not found blood levels significantly greater than zero , nevertheless and important amount of radioactivity was found in feces and urine. The activity was concentrated mainly in the application site in both models

Methylphenidate Transdermal System in Adult ADHD and Impact on Emotional and Oppositional Symptoms

Science.gov (United States)

Marchant, Barrie K.; Reimherr, Frederick W.; Robison, Reid J.; Olsen, John L.; Kondo, Douglas G.

2011-01-01

Objective: This trial evaluated the effect of methylphenidate transdermal system (MTS) on the full spectrum of adult symptoms (attention-disorganization, hyperactivity-impulsivity, emotional dysregulation [ED], and oppositional-defiant disorder [ODD]) found in this disorder. Method: This placebo-controlled, double-blind, flexible-dose, crossover…

In Vitro Drug Transfer Due to Drug Retention in Human Epidermis Pretreated with Application of Marketed Estradiol Transdermal Systems.

Science.gov (United States)

Krishnaiah, Yellela S R; Pavurala, Naresh; Yang, Yang; Manda, Prashanth; Katragadda, Usha; Yang, Yongsheng; Shah, Rakhi; Fang, Guodong; Khan, Mansoor A

2017-08-01

Study objective was to assess skin-to-skin drug transfer potential that may occur due to drug retention in human epidermis (DRE) pretreated with application of estradiol transdermal drug delivery systems (TDDS) and other estradiol transdermal dosage forms (gels and sprays). TDDS (products-A, B, and C) with varying formulation design and composition, and other estradiol transdermal products (gel and spray) were applied to heat separated human epidermis (HSE) and subjected to in vitro drug permeation study. Amounts of DRE were quantified after 24 h. The DRE with product-B was significantly (P  0.05) amounts of DRE. A separate in vitro permeation study was carried out to determine amounts of drug transferred from drug-retaining epidermis to untreated HSE. The amounts of drug transferred, due to DRE after 8 h, with product-C were significantly (P drug transfer due to the DRE after labeled period of using estradiol TDDS, though the clinical relevance of these findings is yet to be determined.

Ultrasound pregnancy

Science.gov (United States)

Pregnancy sonogram; Obstetric ultrasonography; Obstetric sonogram; Ultrasound - pregnancy; IUGR - ultrasound; Intrauterine growth - ultrasound; Polyhydramnios - ultrasound; Oligohydramnios - ultrasound; ...

Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction.

Science.gov (United States)

Xu, Yali; Cui, Hai; Zhu, Qiong; Hua, Xing; Xia, Hongmei; Tan, Kaibin; Gao, Yunhua; Zhao, Jing; Liu, Zheng

2016-01-01

Objective. Blood-brain barrier (BBB) is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p ultrasound-exposed hemisphere (4 ± 1, grade 2) while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction

Directory of Open Access Journals (Sweden)

Yali Xu

2016-01-01

Full Text Available Objective. Blood-brain barrier (BBB is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p<0.01. Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4±1, grade 2 while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

A New Combination of Testosterone and Nestorone Transdermal Gels for Male Hormonal Contraception

Science.gov (United States)

Ilani, Niloufar; Roth, Mara Y.; Amory, John K.; Swerdloff, Ronald S.; Dart, Clint; Page, Stephanie T.; Bremner, William J.; Sitruk-Ware, Regine; Kumar, Narender; Blithe, Diana L.

2012-01-01

Context: Combinations of testosterone (T) and nestorone (NES; a nonandrogenic progestin) transdermal gels may suppress spermatogenesis and prove appealing to men for contraception. Objective: The objective of the study was to determine the effectiveness of T gel alone or combined with NES gel in suppressing spermatogenesis. Design and Setting: This was a randomized, double-blind, comparator clinical trial conducted at two academic medical centers. Participants: Ninety-nine healthy male volunteers participated in the study. Interventions: Volunteers were randomized to one of three treatment groups applying daily transdermal gels (group 1: T gel 10 g + NES 0 mg/placebo gel; group 2: T gel 10 g + NES gel 8 mg; group 3: T gel 10 g + NES gel 12 mg). Main Outcome Variable: The main outcome variable of the study was the percentage of men whose sperm concentration was suppressed to 1 million/ml or less by 20–24 wk of treatment. Results: Efficacy data analyses were performed on 56 subjects who adhered to the protocol and completed at least 20 wk of treatment. The percentage of men whose sperm concentration was 1 million/ml or less was significantly higher for T + NES 8 mg (89%, P male range throughout the treatment period. Adverse effects were minimal in all groups. Conclusion: A combination of daily NES + T gels suppressed sperm concentration to 1 million/ml or less in 88.5% of men, with minimal adverse effects, and may be further studied as a male transdermal hormonal contraceptive. PMID:22791756

Current advances in transdermal delivery of drugs for alzheimer's disease

OpenAIRE

Thuy Trang Nguyen; Vo Van Giau; Tuong Kha Vo

2017-01-01

Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the...

Nanoethosomal transdermal delivery of vardenafil for treatment of erectile dysfunction: optimization, characterization, and in vivo evaluation

Directory of Open Access Journals (Sweden)

Fahmy UA

2015-11-01

Full Text Available Usama A Fahmy Department of Pharmaceutics & Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Vesicular drug delivery systems have recently gained attention as a way of improving dosing accuracy for drugs with poor transdermal permeation. The current study focuses on utilization of the natural biocompatible vesicles to formulate vardenafil nanoethosomes (VRD-NE, for the enhancement of their transdermal permeation and bioavailability. Fifteen formulations were prepared by thin-layer evaporation technique according to Box–Behnken design to optimize formulation variables. The effects of lipid composition, sonication time, and ethanol concentration on particle size and encapsulation efficiency were studied. The diffusion of vardenafil (VRD from the prepared nanoethosomes specified by the design was carried out using automated Franz diffusion cell apparatus. The optimized formula was investigated for in vivo pharmacokinetic parameters compared with oral VRD suspension. Confocal laser scanning microscopy images were used to confirm enhanced diffusion release of VRD in rat skin. The results showed that the optimized formula produced nanoethosomes with an average size of 128 nm and an entrapment efficiency of 76.23%. VRD-NE provided a significant improvement in permeation with an enhancement ratio of 3.05-fold for a film made with optimally formulated VRD-NE compared with a film made with VRD powder. The transdermal bioavailability of VRD from the nanoethosome film was approximately twofold higher than the oral bioavailability from an aqueous suspension. VRD-NE thus provide a promising transdermal drug delivery system. As a result, management of impotence for a longer duration could be achieved with a reduced dosage rate that improves patient tolerability and compliance for the treatment of erectile dysfunction.Keywords: Box–Behnken design, impotence, vesicles, nanoparticles

In vitro transdermal delivery of caffeine, theobromine, theophylline and catechin from extract of Guarana, Paullinia Cupana.

Science.gov (United States)

Heard, Charles M; Johnson, Sarah; Moss, Gary; Thomas, Chris P

2006-07-06

Extracts of guarana (Paullinia cupana) feature as putatively stimulating ingredients in a number of foods, drinks and dietary/herbal supplements. The objective of this work was to investigate in vitro the transdermal delivery of the major pharmacologically active compounds contained in guarana extract. Saturated solutions of guarana were prepared in polyethylene glycol 400 (PEG400), propylene glycol (PG) and H(2)O at 32 degrees C. Guarana extract was also formulated in Duro-tak 2287 transdermal adhesive in a range of concentrations and the diffusional release was determined in addition to adhesive properties. Transdermal delivery across full thickness pig ear skin was investigated in vitro using Franz-type diffusion cells, with reverse-phase HPLC being used for the quantification of the permeation of theobromine (TB), theophylline (TP), (+)-catechin (C) and caffeine (CF). Based upon a combination of release and adhesive property data a patch containing 5.55 mg guarana extract cm(-2) was deemed optimal. The general trend for the delivery of the 4 analytes was: water >5.55 mg cm(-2) patch approximately PG>PEG400. For CF the greatest steady state flux was obtained from the water vehicle: 19 microg cm(-2)h(-1), with approximately 420 microg cm(-2) permeating after 24h. This was some 6x times more than from the drug-in-adhesive patch and 10x greater than PG, a well-known penetration enhancer, and 50x that of the 'regular' excipient PEG400. A water vehicle also provided the greatest delivery of TB (0.45 microg cm(-2) h(-1)), TP (0.022 microg cm(-2) h(-1)), and C (0.10 microg cm(-2) h(-1)). An inverse relationship was noted between lipophilicity and k(p) in each vehicle. The simultaneous transdermal delivery of the major actives of guarana was established, with permeation rates being highly concentration and vehicle dependent.

Novel diffusion cell for in vitro transdermal permeation, compatible with automated dynamic sampling

NARCIS (Netherlands)

Bosman, I.J; Lawant, A.L; Avegaart, S.R.; Ensing, K; de Zeeuw, R.A

The development of a new diffusion cell for in vitro transdermal permeation is described. The so-called Kelder cells were used in combination with the ASPEC system (Automatic Sample Preparation with Extraction Columns), which is designed for the automation of solid-phase extractions (SPE). Instead

Recent developments on ultrasound-assisted organic synthesis in aqueous medium

Directory of Open Access Journals (Sweden)

Banerjee Bubun

2017-01-01

Full Text Available In the recent past, a number of methods were reported on the application of ultrasound in organic reactions for the synthesis of diverse organic scaffolds. On the other hand, as far as green chemistry is concerned, water is the safest of all solvents. Thus, a “strong collaboration” between ultrasonic irradiation and aqueous medium holds the key to the development of an environmentally sustainable protocol. The present review summarizes the latest developments in ultrasound-assisted and water-mediated organic synthesis reported to date.

Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

Directory of Open Access Journals (Sweden)

Marco Antonio Botelho

2014-02-01

Full Text Available OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10% combined with estriol (0.1% + estradiol (0.25% for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05 after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women.

Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

International Nuclear Information System (INIS)

Botelho, Marco Antonio; Queiroz, Dinalva Brito; Barros, Gisele; Guerreiro, Stela; Umbelino, Sonia; Lyra, Arao; Borges, Boniek; Freitas, Allan; Almeida, Jackson Guedes; Quintans Junior, Lucindo

2014-01-01

Objective:to determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. Methods: a total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. Results: an improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04 ± 4.9 to 57.12 ± 4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. Conclusion: the nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. (author)

Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

Energy Technology Data Exchange (ETDEWEB)

Botelho, Marco Antonio; Queiroz, Dinalva Brito; Barros, Gisele; Guerreiro, Stela; Umbelino, Sonia; Lyra, Arao; Borges, Boniek; Freitas, Allan, E-mail: marcobotelho@pq.cnpq.br [Universidade Potiguar, Natal, RN (Brazil). Lab. de Nanotecnologia; Fechine, Pierre [Universidade Federal do Ceara (GQMAT/UFCE), Fortaleza, CE (Brazil). Dept. de Quimica Analitica. Grupo Avancado de Biomateriais em Quimica; Queiroz, Danilo Caldas de [Instituto Federal de Ciencia e Tecnologia (IFCT), Fortaleza, CE (Brazil). Lab. de Biotecnologia; Ruela, Ronaldo [Instituto de Biotecnologia Aplicada (INBIOS), Fortaleza, CE (Brazil); Almeida, Jackson Guedes [Universidade Federal do Vale de Sao Francisco (UNIVALE), Petrolina, PE (Brazil). Fac. de Ciencias Farmaceuticas; Quintans Junior, Lucindo [Universidade Federal de Sergipe (UFSE), Sao Cristovao, SE (Brazil). Dept. de Fisiologia

2014-06-01

Objective:to determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. Methods: a total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. Results: an improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04 ± 4.9 to 57.12 ± 4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. Conclusion: the nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. (author)

Efficacy of a single dose of a transdermal diclofenac patch as pre ...

African Journals Online (AJOL)

2012-01-25

Jan 25, 2012 ... When the side-effects were compared between the groups using a test of proportions, it was not significant. Discussion. The results of our study suggest that when applied at the beginning of surgery, a transdermal patch of diclofenac is as effective as intramuscular diclofenac in prolonging the requirement ...

Formulation Design and Development of a Unani Transdermal Patch for Antiemetic Therapy and Its Pharmaceutical Evaluation

Directory of Open Access Journals (Sweden)

Mohd Nauman Saleem

2016-01-01

Full Text Available The Transdermal Drug Delivery System (TDDS is one of the novel routes for systemic delivery of drugs through intact skin. A transdermal patch (TP is a medicated patch that is placed on skin for delivery of medication through skin into the blood stream. The aim of present study was to formulate and evaluate a Unani transdermal patch that could be used for antiemetic therapy. The incorporation of Unani ingredients, namely, Khardal (Brassica nigra, Zanjabeel (Zingiber officinale, Podina (Mentha arvensis, and Sirka (Vinegar were envisaged. The TP was prepared by solvent evaporation technique and was evaluated for organoleptic characteristics and other physicochemical properties, such as thickness, weight uniformity, folding endurance, moisture content, drug content, and tolerability and acceptability of patch. The in vitro permeation study of the patch was carried out through Franz diffusion cell using egg shell membrane as barrier membrane. Phosphate buffer pH 7.4 was used as dissolution medium and the temperature was maintained at 37 ± 1°C. The in vitro permeation study of the prepared TP indicated a time dependent increase in drug release throughout the study. The percentage of cumulative drug release was found to be 77.38% in 24 hours. The study shows a new approach to work in Unani pharmaceutics.

High intensity focused ultrasound technology, its scope and applications in therapy and drug delivery.

Science.gov (United States)

Phenix, Christopher Peter; Togtema, Melissa; Pichardo, Samuel; Zehbe, Ingeborg; Curiel, Laura

2014-01-01

Ultrasonography is a safe, inexpensive and wide-spread diagnostic tool capable of producing real-time non-invasive images without significant biological effects. However, the propagation of higher energy, intensity and frequency ultrasound waves through living tissues can induce thermal, mechanical and chemical effects useful for a variety of therapeutic applications. With the recent development of clinically approved High Intensity Focused Ultrasound (HIFU) systems, therapeutic ultrasound is now a medical reality. Indeed, HIFU has been used for the thermal ablation of pathological lesions; localized, minimally invasive ultrasound-mediated drug delivery through the transient formation of pores on cell membranes; the temporary disruption of skin and the blood brain barrier; the ultrasound induced break-down of blood clots; and the targeted release of drugs using ultrasound and temperature sensitive drug carriers. This review seeks to engage the pharmaceutical research community by providing an overview on the biological effects of ultrasound as well as highlighting important therapeutic applications, current deficiencies and future directions.

In vitro and ex vivo evaluations on transdermal delivery of the HIV inhibitor IQP-0410.

Directory of Open Access Journals (Sweden)

Anthony S Ham

Full Text Available The aim of this study was to investigate the physicochemical and in vitro/ex vivo characteristics of the pyrmidinedione IQP-0410 formulated into transdermal films. IQP-0410 is a potent therapeutic anti-HIV nonnucleoside reverse transcriptase inhibitor that would be subjected to extensive first pass metabolism, through conventional oral administration. Therefore, IQP-0410 was formulated into ethyl cellulose/HPMC-based transdermal films via solvent casting. In mano evaluations were performed to evaluate gross physical characteristics. In vitro release studies were performed in both Franz cells and USP-4 dissolution vessels. Ex vivo release and permeability assays were performed on human epidermal tissue models, and the permeated IQP-0410 was collected for in vitro HIV-1 efficacy assays in CEM-SS cells and PBMCs. Film formulation D3 resulted in pliable, strong transdermal films that were loaded with 2% (w/w IQP-0410. Composed of 60% (w/w ethyl cellulose and 20% (w/w HPMC, the films contained < 1.2% (w/w of water and were hygroscopic resulting in significant swelling under humid conditions. The water permeable nature of the film resulted in complete in vitro dissolution and drug release in 26 hours. When applied to ex vivo epidermal tissues, the films were non-toxic to the tissue and also were non-toxic to HIV target cells used in the in vitro efficacy assays. Over a 3 day application, the films delivered IQP-0410 through the skin tissue at a zero-order rate of 0.94 ± 0.06 µg/cm(2/hr with 134 ± 14.7 µM collected in the basal media. The delivered IQP-0410 resulted in in vitro EC50 values against HIV-1 of 2.56 ± 0.40 nM (CEM-SS and 0.58 ± 0.03 nM (PBMC. The film formulation demonstrated no significant deviation from target values when packaged in foil pouches under standard and accelerated environmental conditions. It was concluded that the transdermal film formulation was a potentially viable method of administering IQP-0410 that warrants

Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine

Directory of Open Access Journals (Sweden)

Hong X

2013-09-01

Full Text Available Xiaoyun Hong,1,2,* Liangming Wei,3,* Fei Wu,2,* Zaozhan Wu,2 Lizhu Chen,2 Zhenguo Liu,1 Weien Yuan2 1Department of Neurology, Xinhua Hospital, Shanghai, People's Republic of China; 2School of Pharmacy, Shanghai JiaoTong University, Shanghai, People's Republic of China; 3Research Institute of Micro/Nano Science and Technology, Shanghai JiaoTong University, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. Keywords: microneedle, dissolving, biodegradable, sustained release

Use of rivastigmine transdermal patch in the treatment of Alzheimer's disease.

Science.gov (United States)

Winblad, Bengt; Machado, João Carlos

2008-12-01

Cholinesterase inhibitors such as rivastigmine and donepezil exhibit a dose-response relationship, with higher doses of the drugs demonstrating greater efficacy. Transdermal patches provide smooth continuous drug delivery, with the potential to offer efficacious levels of drug exposure while avoiding the peaks and troughs associated with side effects. As a small, lipophilic and hydrophilic molecule, rivastigmine (C14H22N2O2) is chemically well-suited to transdermal delivery. The technology underlying the rivastigmine patch allows it to be discreetly small and thin. The target dose 9.5 mg/24 h rivastigmine patch has a diameter of just 3.5 cm and a surface area of 10 cm2. A large randomized controlled trial has demonstrated that the target dose 9.5 mg/24 h rivastigmine patch provided similar efficacy to the highest rivastigmine capsule doses, yet with three times fewer reports of nausea and vomiting. Thus, the rivastigmine patch enables quick and easy access to high dose efficacy. The skin tolerability profile is good, and the patch has demonstrated excellent adhesion. The apparent success of rivastigmine patch, in terms of clinical utility and patient acceptability, suggests that it may mark the next generation of dementia treatment.

Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration.

Science.gov (United States)

Berkó, Szilvia; Szűcs, Kálmán F; Balázs, Boglárka; Csányi, Erzsébet; Varju, Gábor; Sztojkov-Ivanov, Anita; Budai-Szűcs, Mária; Bóta, Judit; Gáspár, Róbert

2016-01-01

Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Both intravenously and EP-administered neostigmine (0.2-66.7 μg/kg) increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 μg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice.

Patient-controlled analgesia : therapeutic interventions using transdermal electro-activated and electro-modulated drug delivery

NARCIS (Netherlands)

Indermun, S.; Choonara, Y.E.; Kumar, P.; Du Toit, L.C.; Modi, G.; Luttge, R.; Pillay, V.

2014-01-01

Chronic pain poses a major concern to modern medicine and is frequently undertreated, causing suffering and disability. Patient-controlled analgesia, although successful, does have limitations. Transdermal delivery is the pivot to which analgesic research in drug delivery has centralized, especially

In Vitro Investigation of the Individual Contributions of Ultrasound-Induced Stable and Inertial Cavitation in Targeted Drug Delivery.

Science.gov (United States)

Gourevich, Dana; Volovick, Alexander; Dogadkin, Osnat; Wang, Lijun; Mulvana, Helen; Medan, Yoav; Melzer, Andreas; Cochran, Sandy

2015-07-01

Ultrasound-mediated targeted drug delivery is a therapeutic modality under development with the potential to treat cancer. Its ability to produce local hyperthermia and cell poration through cavitation non-invasively makes it a candidate to trigger drug delivery. Hyperthermia offers greater potential for control, particularly with magnetic resonance imaging temperature measurement. However, cavitation may offer reduced treatment times, with real-time measurement of ultrasonic spectra indicating drug dose and treatment success. Here, a clinical magnetic resonance imaging-guided focused ultrasound surgery system was used to study ultrasound-mediated targeted drug delivery in vitro. Drug uptake into breast cancer cells in the vicinity of ultrasound contrast agent was correlated with occurrence and quantity of stable and inertial cavitation, classified according to subharmonic spectra. During stable cavitation, intracellular drug uptake increased by a factor up to 3.2 compared with the control. Reported here are the value of cavitation monitoring with a clinical system and its subsequent employment for dose optimization. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Ultrasound-mediated drug delivery to the brain: principles, progress and prospects

NARCIS (Netherlands)

Dasgupta, I.; Liu, M.; Ojha, T.; Storm, Gerrit; Kiessling, F.; Lammers, Twan Gerardus Gertudis Maria

2016-01-01

The blood–brain barrier (BBB) limits drug delivery to the central nervous system. When combined with microbubbles, ultrasound can transiently permeate blood vessels in the brain. This approach, which can be referred to as sonoporation or sonopermeabilization, holds significant promise for shuttling

A dose-finding, cross-over study to evaluate the effect of a Nestorone®/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women.

Science.gov (United States)

Brache, Vivian; Merkatz, Ruth; Kumar, Narender; Jesam, Cristian; Sussman, Heather; Hoskin, Elena; Roberts, Kevin; Alami, Mohcine; Taylor, Deshawn; Jorge, Aidelis; Croxatto, Horacio; Lorange, Ellen; Mishell, Daniel R; Sitruk-Ware, Regine

2015-10-01

This study aims to determine the lowest effective of three Nestorone (NES)/estradiol (E2) transdermal gel doses to ensure ovulation suppression in 90-95% of cycles. This was a randomized, open-label, three-treatment-period cross-over study to evaluate the effects of NES/E2 transdermal gel on ovulation inhibition, suppression of follicular growth and pharmacokinetic parameters. The doses were low (1.5 mg NES/0.5 mg E2), medium (3.0 mg NES/1.0 mg E2) and high (4.5 mg NES/1.5 mg E2). Participants applied gel daily to a fixed area on the abdomen for 21 consecutive days. They were interviewed regarding their experiences using the gel. Eighteen participants were randomized; 16 completed the study. Median NES C(max) values for low, medium and high dose groups at day 21 were 318.6 pmol/L, 783.0 pmol/L and 1063.8 pmol/L, respectively. Median maximum follicular diameter was higher with the lowest dose with 16.2 mm versus 10.0 and 10.4 mm with the medium and high doses, respectively. Among adherent participants, ovulation was inhibited in all dose groups, except for one participant in the medium dose (6.7%) that had luteal activity and an ultrasound image suggestive of a luteinized unruptured follicle. There were few reports of unscheduled bleeding, with more episodes reported for the lower dose. Adverse events were mild, and no skin irritation was reported from gel application. While all three doses blocked ovulation effectively and were evaluated as safe and acceptable, the medium dose was considered the lowest effective dose based on a more adequate suppression of follicular development. Further development of this novel contraceptive delivering NES and E2 is warranted and has potential for improved safety compared to ethinyl-estradiol-based methods. Copyright © 2015 Elsevier Inc. All rights reserved.

Prostate Ultrasound

Medline Plus

Full Text Available ... Physician Resources Professions Site Index A-Z Ultrasound - Prostate Ultrasound of the prostate uses sound waves to ... Ultrasound Imaging? What is Ultrasound Imaging of the Prostate? Ultrasound is safe and painless, and produces pictures ...

WE-G-12A-01: High Intensity Focused Ultrasound Surgery and Therapy

Energy Technology Data Exchange (ETDEWEB)

Farahani, K [National Cancer Institute, Rockville, MD (United States); O' Neill, B [The Methodist Hospital Research Institute, Houston, TX (United States)

2014-06-15

More and more emphasis is being made on alternatives to invasive surgery and the use of ionizing radiation to treat various diseases including cancer. Novel screening, diagnosis, treatment and monitoring of response to treatment are also hot areas of research and new clinical technologies. Ultrasound(US) has gained traction in all of the aforementioned areas of focus. Especially with recent advances in the use of ultrasound to noninvasively treat various diseases/organ systems. This session will focus on covering MR-guided focused ultrasound and the state of the art clinical applications, and the second speaker will survey the more cutting edge technologies e.g. Focused Ultrasound (FUS) mediated drug delivery, principles of cavitation and US guided FUS. Learning Objectives: Fundamental physics and physical limitations of US interaction with tissue and nanoparticles The alteration of tissue transport using focused ultrasound US control of nanoparticle drug carriers for targeted release The basic principles of MRI-guided focused ultrasound (MRgFUS) surgery and therapy the current state of the art clinical applications of MRgFUS requirements for quality assurance and treatment planning.

Efficacy of biorhythmic transdermal combined hormone treatment in relieving climacteric symptoms: a pilot study

Directory of Open Access Journals (Sweden)

B Formby

2011-02-01

Full Text Available B Formby, F SchmidtThe Rasmus Institute for Medical Research, Program in Reproductive Endocrinology, Santa Barbara, CA, USAObjective: To evaluate the efficacy of a combination of bioidentical combined 17β-estradiol and progesterone transdermal delivery system (lipophilic emulsion-type base to relieve climacteric symptoms. The hormonal replacement was given during a period of 6 months at four different cyclic doses to mimic the normal ovary secretory pattern.Design: An open, randomized, comparative, between-patient trial conducted over 6 months in 29 menopausal women with climacteric symptoms assessed with the Kupperman index at baseline and during treatments. Saliva and serum values of 17β-estradiol and progesterone were quantitated before treatment and after 3 and 6 months. Pharmacokinetic data following transdermal administration of 17β-estradiol (0.3 mg, daily and progesterone (100 mg, daily were calculated from saliva levels using high-performance liquid chromatography analysis.Results: Improvement in climacteric symptoms was reported in 93% of women evaluated before and after 3 and 6 months of treatment. Values of saliva 17β-estradiol increased after 6 months from 0.6 ± 0.3 pg/mL to 14.1 ± 3.3 pg/mL, and the values of serum 17β-estradiol increased from 3.3 ± 2.8 pg/mL to 80.6 ± 21.9 pg/mL. Of responders, 88% characterized symptom relief as complete. No adverse health-related events were attributed to the bioidentical hormone therapy. Time to maximum saliva concentrations (Tmax, in all experimental cases, was observed after 6 hours. Baseline values were reached within 24 hours, indicating a diurnal rhythm of 17β-estradiol seen in normally cyclic women over the 24-hour period, ie, its daily biological rhythm.Conclusion: Percutaneous absorption of 17β-estradiol, as well as the absorption of progesterone, was associated with relief of climacteric symptoms. The cyclical transdermal delivery of combined bioidentical hormones may be

Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration

Directory of Open Access Journals (Sweden)

Berkó S

2016-05-01

Full Text Available Szilvia Berkó,1,* Kálmán F Szűcs,2,* Boglárka Balázs,1,3 Erzsébet Csányi,1 Gábor Varju,4 Anita Sztojkov-Ivanov,2 Mária Budai-Szűcs,1 Judit Bóta,2 Róbert Gáspár2 1Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; 2Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; 3Gedeon Richter Plc., Budapest, 4Dr Derm Clinic of Anti-Aging Dermatology, Aesthetic Laser and Plastic Surgery, Budapest, Hungary *These authors contributed equally to this work Purpose: Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. Methods: The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Results: Both intravenously and EP-administered neostigmine (0.2–66.7 µg/kg increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 µg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. Conclusion: The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice. Keywords: transdermal

A prospective randomized comparative study of the effects of intranasal and transdermal 17 β-estradiol on postmenopausal symptoms and vaginal cytology

Directory of Open Access Journals (Sweden)

Odabasi A

2007-01-01

Full Text Available Context: Investigating the adverse effects of oral hormone replacement therapy (HRT, the clinical effectiveness of alternative combinations and route of administrations. Aim: To compare the effects of intranasal and transdermal 17β-estradiol combined with vaginal progesterone on vasomotor symptoms and vaginal cytology. Settings and Design: A 12-week, prospective, randomized comparative study was conducted between July 2005 and September 2006. Materials and Methods: Eighty postmenopausal women aged between 42-57 years, who had scores of ≥1.7 on the menopause rating scale-I (MRS-I items "1-6", were randomly assigned to receive intranasal (300 µg/day, n =40 or transdermal (50 µg/day, n =40 17β-estradiol continuously. All patients also received a vaginal progesterone gel twice weekly. Vasomotor symptoms were evaluated at weeks 0, 4, 8 and 12. Vaginal maturation index (VMI was evaluated at weeks 0 and 12 of the study. Statistical Analyses: The Mann-Whitney U and the Wilcoxon tests were used. P < 0.05 was regarded as significant. Results: Thirty-two women in the intranasal and 29 women in the transdermal group completed the study. The total score of the MRS, the sum-scores of Factor 1 "HOT FLUSHES" and Factor 2 "PSYCHE" significantly decreased in both groups at week 4. Factor 3 "ATROPHY" scores significantly decreased only in the transdermal group at week 12. The VMI showed no changes within and between the two groups at the end of the study. Conclusion: Intranasal and transdermal 17β-estradiol combined with vaginal progesterone gel as a continuous HRT caused a similar decrease in vasomotor symptoms but did not have any significant effect on VMI after 12 weeks of treatment in this study population.

Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent.

Science.gov (United States)

Unger, E C; McCreery, T P; Sweitzer, R H; Caldwell, V E; Wu, Y

1998-12-01

Paclitaxel-carrying lipospheres (MRX-552) were developed and evaluated as a new ultrasound contrast agent for chemotherapeutic drug delivery. Paclitaxel was suspended in soybean oil and added to an aqueous suspension of phospholipids in vials. The headspace of the vials was replaced with perfluorobutane gas; the vials were sealed, and they were agitated at 4200 rpm on a shaking device. The resulting lipospheres containing paclitaxel were studied for concentration, size, acute toxicity in mice, and acoustic activity and drug release with ultrasound. Lipospheres containing sudan black dye were produced to demonstrate the acoustically active liposphere (AAL)-ultrasound release concept. Acoustically active lipospheres containing paclitaxel had a mean particle count of approximately 1 x 10(9) particles per mL and a mean size of 2.9 microns. Acute toxicity studies in mice showed a 10-fold reduction in toxicity for paclitaxel in AALs compared with free paclitaxel. The AALs reflected ultrasound as a contrast agent. Increasing amounts of ultrasound energy selectively ruptured the AALs and released the paclitaxel. Acoustically active lipospheres represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of AALs for ultrasound-mediated drug delivery.

Expanding the domain of drug delivery for HIV prevention: exploration of the transdermal route.

Science.gov (United States)

Puri, Ashana; Sivaraman, Arunprasad; Zhang, Wei; Clark, Meredith R; Banga, Ajay K

2017-01-01

Constant efforts for HIV prevention using antiretroviral drugs, pre- and postexposure prophylactic agents, and microbicides are being made by researchers. Drug-delivery systems such as oral tablets and coitally dependent vaginal gels are short acting, require daily application, and are associated with user adherence issues, whereas the coitally independent systems such as injectables and biodegradable implants are long acting, lasting several months, during which time the termination of prophylaxis is impractical in case of adverse effects. An effective drug-delivery system to be used for an intermediate duration, if available, would be an attractive alternative option for users in terms of adherence. Transdermal delivery systems, overcoming most of the limitations of the other routes of administration and aiming to provide sustained delivery of drugs through skin, may be explored for HIV prevention. Passive and physical enhancement techniques may be designed strategically to improve the transdermal delivery of HIV preventive agents.

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... specific content. Related Articles and Media Sonohysterography Ultrasound - Abdomen Children's (Pediatric) Ultrasound - Abdomen Obstetric Ultrasound Ultrasound - Prostate Kidney and ...

Film forming systems for topical and transdermal drug delivery

Directory of Open Access Journals (Sweden)

Kashmira Kathe

2017-11-01

Full Text Available Skin is considered as an important route of administration of drugs for both local and systemic effects. The effectiveness of topical therapy depends on the physicochemical properties of the drug and adherence of the patient to the treatment regimen as well as the system's ability to adhere to skin during the therapy so as to promote drug penetration through the skin barrier. Conventional formulations for topical and dermatological administration of drugs have certain limitations like poor adherence to skin, poor permeability and compromised patient compliance. For the treatment of diseases of body tissues and wounds, the drug has to be maintained at the site of treatment for an effective period of time. Topical film forming systems are such developing drug delivery systems meant for topical application to the skin, which adhere to the body, forming a thin transparent film and provide delivery of the active ingredients to the body tissue. These are intended for skin application as emollient or protective and for local action or transdermal penetration of medicament for systemic action. The transparency is an appreciable feature of this polymeric system which greatly influences the patient acceptance. In the current discussion, the film forming systems are described as a promising choice for topical and transdermal drug delivery. Further the various types of film forming systems (sprays/solutions, gels and emulsions along with their evaluation parameters have also been reviewed.

Development of antimigraine transdermal delivery systems of pizotifen malate.

Science.gov (United States)

Serna-Jiménez, C E; del Rio-Sancho, S; Calatayud-Pascual, M A; Balaguer-Fernández, C; Femenía-Font, A; López-Castellano, A; Merino, V

2015-08-15

The aim of this study was to develop and evaluate a transdermal delivery system of pizotifen malate. Pizotifen is frequently used in the preventive treatment of migraine, but is also indicated in eating disorders. In the course of the project, the effects of chemical enhancers such as ethanol, 1,8-cineole, limonene, azone and different fatty acids (decanoic, decenoic, dodecanoic, linoleic and oleic acids) were determined, first using a pizotifen solution. Steady state flux, diffusion and partition parameters were estimated by fitting the Scheuplein equation to the data obtained. Among the chemical enhancers studied, decenoic acid showed the highest enhancement activity, which seemed to be due to the length of its alkyl chain and unsaturation at the 9th carbon. The influence of iontophoresis and the involvement of electrotransport in said process was determined. The absorption profile obtained with iontophoresis was similar to that obtained with fatty acids and terpenes, though skin deposition of the drug was lower with the former. Transdermal delivery systems (TDS) of pizotifen were manufactured by including chemical enhancers, decenoic acid or oleic acid, and were subsequently characterized. When the results obtained with solutions were compared with those obtained with the TDS, a positive enhancement effect was observed with the latter with respect to the partitioning and diffusion of the drug across the skin. Our findings endorse the suitability of our TDS for delivering therapeutic amounts of pizotifen malate. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of Microneedle Type on Transdermal Permeation of Rizatriptan.

Science.gov (United States)

Uppuluri, Chandrateja; Shaik, Ashraf Sultana; Han, Tao; Nayak, Atul; Nair, Karthik J; Whiteside, Benjamin R; Nalluri, Buchi N; Das, Diganta B

2017-07-01

The present study was aimed to investigate the effect of salient microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation of rizatriptan (RIZ). Studies were carried out using two types of MN devices viz. AdminPatch® arrays (ADM) (0.6, 0.9, 1.2 and 1.5 mm lengths) and laboratory-fabricated polymeric MNs (PMs) of 0.6 mm length. In the case of the PMs, arrays were applied three times at different places within a 1.77-cm 2 skin area (PM-3) to maintain the MN density closer to 0.6 mm ADM. Histological studies revealed that PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 4.9- and 4.2-fold increases in the RIZ steady-state flux values were observed with 1.5 mm ADM and PM-3 applications when compared to the passive studies. A good correlation between different dimensionless parameters like the amount of RIZ permeated (C t /C s ), thickness (h/L) and surface area (S a /L 2 ) of the skin was observed with scaling analyses. Numerical simulations provided further information regarding the distribution of RIZ in MN-treated skin after application of different MNs. Overall, the study suggests that MN application enhances the RIZ transdermal permeation and the geometrical parameters of MNs play an important role in the degree enhancement.

Methylphenidate Transdermal System in Adults with Past Stimulant Misuse: An Open-Label Trial

Science.gov (United States)

McRae-Clark, Aimee L.; Brady, Kathleen T.; Hartwell, Karen J.; White, Kathleen; Carter, Rickey E.

2011-01-01

Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the…

Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the Stratum Corneum

Directory of Open Access Journals (Sweden)

Ahlam Zaid Alkilani

2015-10-01

Full Text Available The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies.

Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the stratum corneum

Science.gov (United States)

Zaid Alkilani, Ahlam; McCrudden, Maelíosa T.C.; Donnelly, Ryan F.

2015-01-01

The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies. PMID:26506371

Ultrasound Microbubble Treatment Enhances Clathrin-Mediated Endocytosis and Fluid-Phase Uptake through Distinct Mechanisms.

Directory of Open Access Journals (Sweden)

Farnaz Fekri

Full Text Available Drug delivery to tumors is limited by several factors, including drug permeability of the target cell plasma membrane. Ultrasound in combination with microbubbles (USMB is a promising strategy to overcome these limitations. USMB treatment elicits enhanced cellular uptake of materials such as drugs, in part as a result of sheer stress and formation of transient membrane pores. Pores formed upon USMB treatment are rapidly resealed, suggesting that other processes such as enhanced endocytosis may contribute to the enhanced material uptake by cells upon USMB treatment. How USMB regulates endocytic processes remains incompletely understood. Cells constitutively utilize several distinct mechanisms of endocytosis, including clathrin-mediated endocytosis (CME for the internalization of receptor-bound macromolecules such as Transferrin Receptor (TfR, and distinct mechanism(s that mediate the majority of fluid-phase endocytosis. Tracking the abundance of TfR on the cell surface and the internalization of its ligand transferrin revealed that USMB acutely enhances the rate of CME. Total internal reflection fluorescence microscopy experiments revealed that USMB treatment altered the assembly of clathrin-coated pits, the basic structural units of CME. In addition, the rate of fluid-phase endocytosis was enhanced, but with delayed onset upon USMB treatment relative to the enhancement of CME, suggesting that the two processes are distinctly regulated by USMB. Indeed, vacuolin-1 or desipramine treatment prevented the enhancement of CME but not of fluid phase endocytosis upon USMB, suggesting that lysosome exocytosis and acid sphingomyelinase, respectively, are required for the regulation of CME but not fluid phase endocytosis upon USMB treatment. These results indicate that USMB enhances both CME and fluid phase endocytosis through distinct signaling mechanisms, and suggest that strategies for potentiating the enhancement of endocytosis upon USMB treatment may

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... Ultrasound - Abdomen Obstetric Ultrasound Ultrasound - Prostate Kidney and Bladder Stones Abnormal Vaginal Bleeding Ovarian Cancer Images related to Ultrasound - Pelvis Sponsored by Please ...

The Ultrasound pattern sum score - UPSS. A new method to differentiate acute and subacute neuropathies using ultrasound of the peripheral nerves.

Science.gov (United States)

Grimm, Alexander; Décard, Bernhard F; Axer, Hubertus; Fuhr, Peter

2015-11-01

Ultrasound differentiation of neuropathies is a great challenge. We, therefore, suggest a standardized score to operationalize differentiation between several acute and subacute onset neuropathies. We retrospectively analyzed the ultrasound data of 61 patients with acute or subacute neuropathies, e.g. chronic immune-mediated neuropathies, Guillain-Barré syndrome (GBS), and axonal/vasculitic neuropathies. We compared these data to 28 healthy controls. Based on these results an ultrasound pattern sum score (UPSS) with three sub-scores (UPS-A for the sensorimotor nerves, UPS-B for the cervical roots and the vagal nerve and UPS-C for the sural nerve) was developed. Afterwards, the applicability of the score was prospectively validated in 10 patients with chronic neuropathies and in 14 patients with unknown acute and subacute PNP before performing additional tests. UPS-A and UPSS were significantly higher in CIDP than in other neuropathies and controls (p85%. Vasculitic neuropathies showed an intermediate type of UPSS compared to other axonal neuropathies (ppower to the method of the peripheral nerve ultrasound. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... Children's (Pediatric) Ultrasound - Abdomen Obstetric Ultrasound Ultrasound - Prostate Kidney and Bladder Stones Abnormal Vaginal Bleeding Ovarian Cancer Images related to Ultrasound - Pelvis Sponsored by Please ...

A comparative study on the transdermal penetration effect of gaseous and aqueous plasma reactive species

Science.gov (United States)

Liu, Xin; Gan, Lu; Ma, Mingyu; Zhang, Song; Liu, Jingjing; Chen, Hongxiang; Liu, Dawei; Lu, Xinpei

2018-02-01

To improve the depth of plasma active species in the skin, it is very important to develop skin disease treatment using plasma. In this article, an air plasma source was used to work directly with the skin of a mouse. A tortuous pathway, hair follicles, electroporation and a microneedle do not aid the transdermal delivery of gaseous plasma active species, therefore these gaseous plasma active species cannot penetrate mouse skin with a thickness of ~0.75 mm. The plasma activated water (PAW) produced by the air plasma source was used to study the transdermal penetration of the aqueous plasma activated species. This aqueous plasma activated species can penetrate the skin through hair follicles, intercellular and transcellular routes. The pH of the PAW did not affect the penetration efficiency of the aqueous plasma active species.

The effect of transdermal nicotine patches on sleep and dreams.

Science.gov (United States)

Page, F; Coleman, G; Conduit, R

2006-07-30

This study was undertaken to determine the effect of 24-h transdermal nicotine patches on sleep and dream mentation in 15 smokers aged 20 to 33. Utilising a repeated measures design, it was found that more time awake and more ASDA micro-arousals occurred while wearing the nicotine patch compared to placebo. Also, the percentage of REM sleep decreased, but REM latency and the proportion of time spent in NREM sleep stages did not change significantly. Dream reports containing visual imagery, visual imagery ratings and the number of visualizable nouns were significantly greater from REM compared to Stage 2 awakenings, regardless of patch condition. However, a general interaction effect was observed. Stage 2 dream variables remained equivalent across nicotine and placebo conditions. Within REM sleep, more dream reports containing visual imagery occurred while wearing the nicotine patch, and these were rated as more vivid. The greater frequency of visual imagery reports and higher imagery ratings specifically from REM sleep suggests that previously reported dreaming side effects from 24-h nicotine patches may be specific to REM sleep. Combined with previous animal studies showing that transdermally delivered nicotine blocks PGO activity in REM sleep, the current results do no appear consistent with PGO-based hypotheses of dreaming, such as the Activation-Synthesis (AS) or Activation, Input and Modulation (AIM) models.

Carbon nanotubes buckypapers for potential transdermal drug delivery

International Nuclear Information System (INIS)

Schwengber, Alex; Prado, Héctor J.; Zilli, Darío A.; Bonelli, Pablo R.

2015-01-01

Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT–drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. - Highlights: • Drug loaded buckypapers from carbon nanotubes were prepared and characterized. • Their potentialities for transdermal drug delivery applications were evaluated. • Characteristics of carbon nanotubes and the structure of the drug affected release • A higher carbon nanotube:drug mass ratio decelerated release • Up to one week controlled release profiles were obtained for the drug flurbiprofen

Carbon nanotubes buckypapers for potential transdermal drug delivery

Energy Technology Data Exchange (ETDEWEB)

Schwengber, Alex [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Prado, Héctor J. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Cátedra de Tecnología Farmacéutica II, Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, C1033AAJ Buenos Aires (Argentina); Zilli, Darío A. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Bonelli, Pablo R. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, C1033AAJ Buenos Aires (Argentina); and others

2015-12-01

Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT–drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. - Highlights: • Drug loaded buckypapers from carbon nanotubes were prepared and characterized. • Their potentialities for transdermal drug delivery applications were evaluated. • Characteristics of carbon nanotubes and the structure of the drug affected release • A higher carbon nanotube:drug mass ratio decelerated release • Up to one week controlled release profiles were obtained for the drug flurbiprofen.

Prehospital Ultrasound

Directory of Open Access Journals (Sweden)

Jen-Tang Sun

2014-06-01

Full Text Available Ultrasound is a commonly used diagnostic tool in clinical conditions. With recent developments in technology, use of portable ultrasound devices has become feasible in prehospital settings. Many studies also proved the feasibility and accuracy of prehospital ultrasound. In this article, we focus on the use of prehospital ultrasound, with emphasis on trauma and chest ultrasound.

Evaluation of the Percutaneous Absorption of Ketamine HCl, Gabapentin, Clonidine HCl, and Baclofen, in Compounded Transdermal Pain Formulations, Using the Franz Finite Dose Model.

Science.gov (United States)

Bassani, August S; Banov, Daniel

2016-02-01

This study evaluates the ability of four commonly used analgesics (ketamine HCl, gabapentin, clonidine HCl, and baclofen), when incorporated into two transdermal compounding bases, Lipoderm and Lipoderm ActiveMax, to penetrate human cadaver trunk skin in vitro, using the Franz finite dose model. In vitro experimental study. Methods. Ketamine HCl 5% w/w, gabapentin 10% w/w, clonidine HCl 0.2% w/w, and baclofen 2% w/w were compounded into two transdermal bases, Lipoderm and Lipoderm ActiveMax. Each compounded drug formulation was tested on skin from three different donors and three replicate skin sections per donor. The Franz finite dose model was used in this study to evaluate the percutaneous absorption and distribution of drugs within each formulation. Rapid penetration to peak flux was detected for gabapentin and baclofen at approximately 1 hour after application. Clonidine HCl also had a rapid penetration to peak flux occurring approximately 1 hour after application and had a secondary peak at approximately 40 hours. Ketamine HCl exhibited higher overall absorption rates than the other drugs, and peaked at 6–10 hours. Similar patterns of drug distribution within the skin were also observed using both transdermal bases. This study suggests that the combination of these 4 analgesic drugs can be successfully delivered transdermally, using either Lipoderm or Lipoderm ActiveMax. Compounded transdermal drug preparations may then provide physicians with an alternative to traditional oral pain management regimens that can be personalized to the specific patient with the potential for enhanced pain control.

Transfection of CXCR-4 using microbubble-mediated ultrasound irradiation and liposomes improves the migratory ability of bone marrow stromal cells.

Science.gov (United States)

Wang, Gong; Zhuo, Zhongxiong; Zhang, Qian; Xu, Yali; Wu, Shengzheng; Li, Lu; Xia, Hongmei; Gao, Yunhua

2015-01-01

Bone marrow stromal cells (BMSCs) have proven useful for the treatment of various human diseases and injuries. However, their reparative capacity is limited by their poor migration and homing ability, which are primarily dependent on the SDF-1/CXCR4 axis. Most subcultured BMSCs lack CXCR4 receptor expression on the cell surface and exhibit impaired migratory capacity. To increase responsiveness to SDF-1 and promote cell migration and survival of cultured BMSCs, we used a combination of ultrasound-targeted microbubble destruction (UTMD) and liposomes to increase CXCR4 expression in vitro. We isolated and cultured rat BMSCs to their third passage and transduced them with recombinant plasmid pDsRed-CXCR4 using microbubble-mediated ultrasound irradiation and liposomes. Compared to some viral vectors, the method we employed here resulted in significantly better transfection efficiency, CXCR4 expression, and technical reproducibility. The benefits of this approach are likely due to the combination of "sonoporation" caused by shockwaves and microjet flow resulting from UTMD-generated cavitation. Following transfection, we performed a transwell migration assay and found that the migration ability of CXCR4-modified BMSCs was 9-fold higher than controls. The methods we describe here provide an effective, safe, non-viral means to achieve high levels of CXCR4 expression. This is associated with enhanced migration of subcultured BMSCs and may be useful for clinical application as well.

Flexible and Stretchable Microneedle Patches with Integrated Rigid Stainless Steel Microneedles for Transdermal Biointerfacing.

Science.gov (United States)

Rajabi, Mina; Roxhed, Niclas; Shafagh, Reza Zandi; Haraldson, Tommy; Fischer, Andreas Christin; Wijngaart, Wouter van der; Stemme, Göran; Niklaus, Frank

2016-01-01

This paper demonstrates flexible and stretchable microneedle patches that combine soft and flexible base substrates with hard and sharp stainless steel microneedles. An elastomeric polymer base enables conformal contact between the microneedle patch and the complex topography and texture of the underlying skin, while robust and sharp stainless steel microneedles reliably pierce the outer layers of the skin. The flexible microneedle patches have been realized by magnetically assembling short stainless steel microneedles into a flexible polymer supporting base. In our experimental investigation, the microneedle patches were applied to human skin and an excellent adaptation of the patch to the wrinkles and deformations of the skin was verified, while at the same time the microneedles reliably penetrate the surface of the skin. The unobtrusive flexible and stretchable microneedle patches have great potential for transdermal biointerfacing in a variety of emerging applications such as transdermal drug delivery, bioelectric treatments and wearable bio-electronics for health and fitness monitoring.

Influence of electrical and chemical factors on transdermal iontophoretic delivery of three diclofenac salts.

Science.gov (United States)

Fang, J Y; Wang, R J; Huang, Y B; Wu, P C; Tsai, Y H

2001-04-01

The aim of this present study was to investigate the in vitro transdermal iontophoretic delivery of three diclofenac salts--diclofenac sodium (DFS), diclofenac potassium (DFP), and diclofenac diethylammonium (DFD). A series of physicochemical and electrical variables which might affect iontophoretic permeation of diclofenac salts was studied. Application of 0.3 mA/cm2 current density significantly increased the transdermal flux of diclofenac salts as compared to passive transport. The iontophoretic enhancement increased in the order of DFS>DFP>DFD. The permeability coefficient of diclofenac salts all decreased with increasing donor concentration during iontophoresis. The addition of buffer ions and salt ions such as NaCl, KCl, and C4H12ClN reduced the permeation of diclofenac salts due to competition. However, this effect was lesser for DFD than for DFS and DFP. Comparing the various application modes of iontophoresis, the discontinuous on/off mode showed lower but more constant flux than the continuous mode.

Transdermal fentanyl for pain caused by radiotherapy in head and neck cancer patients treated in an outpatient setting. A multicenter trial in Taiwan

International Nuclear Information System (INIS)

Chang, J.T.C.; Lin Chienyu; Wang Hungming; Lin Jinching; Lee Moonsing; Chen Yujen

2010-01-01

This study evaluated the efficacy and safety of transdermal fentanyl in the outpatient treatment of head and neck cancer patients with pain caused by radiotherapy. Patients with a visual analogue scale score ≥4 were invited to participate in the study. The following variables were collected: visual analogue scale, the Brief Pain Inventory, concomitant pain medications and adverse effects. A total of 163 head and neck cancer patients were enrolled (148 males and 15 females; median age, 53 years; age range, 21-72 years). Seventy-two (44%) patients had a visual analogue scale score >6 at enrollment, despite the use of non-steroidal anti-inflammatory drugs or weak opioids. Ninety-four (57.7%) patients received concurrent chemotherapy. A total of 88 patients completed the study, whereas 55 underwent a drop-out by side effects. The most frequently reported adverse events were vomiting (23.9%) and nausea (16.6%). Treatment with transdermal fentanyl resulted in a significant decrease in visual analogue scale and Brief Pain Inventory scores that persisted during treatment. In the overall efficacy evaluation, the pain-alleviating effect, the easiness of application and the overall impression of transdermal fentanyl were rated as good by 54.5%, 65.9% and 59.1% of the completers, respectively. Effects of transdermal fentanyl were rated as good by 64.8% of the investigators. Our data provide evidence that transdermal fentanyl is effective and relatively easy to use for outpatient treatment of pain control in head and neck cancer patients following radiotherapy in selected patients. Reduction of side effects and effective pain management need to be paramount in the management of head and neck cancer patients undergoing radiotherapy. (author)

Iontophoretic transdermal drug delivery: a multi-layered approach.

Science.gov (United States)

Pontrelli, Giuseppe; Lauricella, Marco; Ferreira, José A; Pena, Gonçalo

2017-12-11

We present a multi-layer mathematical model to describe the transdermal drug release from an iontophoretic system. The Nernst-Planck equation describes the basic convection-diffusion process, with the electric potential obtained by solving the Laplace's equation. These equations are complemented with suitable interface and boundary conditions in a multi-domain. The stability of the mathematical problem is discussed in different scenarios and a finite-difference method is used to solve the coupled system. Numerical experiments are included to illustrate the drug dynamics under different conditions. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

Rapid, low cost prototyping of transdermal devices for personal healthcare monitoring

Directory of Open Access Journals (Sweden)

Sanjiv Sharma

2017-04-01

Full Text Available The next generation of devices for personal healthcare monitoring will comprise molecular sensors to monitor analytes of interest in the skin compartment. Transdermal devices based on microneedles offer an excellent opportunity to explore the dynamics of molecular markers in the interstitial fluid, however good acceptability of these next generation devices will require several technical problems associated with current commercially available wearable sensors to be overcome. These particularly include reliability, comfort and cost. An essential pre-requisite for transdermal molecular sensing devices is that they can be fabricated using scalable technologies which are cost effective.We present here a minimally invasive microneedle array as a continuous monitoring platform technology. Method for scalable fabrication of these structures is presented. The microneedle arrays were characterised mechanically and were shown to penetrate human skin under moderate thumb pressure. They were then functionalised and evaluated as glucose, lactate and theophylline biosensors. The results suggest that this technology can be employed in the measurement of metabolites, therapeutic drugs and biomarkers and could have an important role to play in the management of chronic diseases. Keywords: Microneedles, Minimally invasive sensors, Continuous glucose monitoring (CGM, Continuous lactate monitoring (CLM, Interstitial therapeutic drug monitoring (iTDM

Use and cardiovascular safety of transdermal and other granisetron preparations in cancer management

International Nuclear Information System (INIS)

Mason, Jay W; Moon, Thomas E

2013-01-01

5-HT 3 antagonists have been available as oral and intravenous preparations for decades. The availability more recently of transdermal granisetron and the anticipated availability of a subcutaneous granisetron preparation have provided helpful alternatives to patients, and these preparations have been shown to have less potential to prolong QT than other drugs in the class

Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats

Science.gov (United States)

Song, Zhaojun; Wang, Zhigang; Shen, Jieliang; Xu, Shengxi; Hu, Zhenming

2017-01-01

Background Spinal cord injuries (SCIs) can cause severe disability or death. Treatment options include surgical intervention, drug therapy, and stem cell transplantation. However, the efficacy of these methods for functional recovery remains unsatisfactory. Purpose This study was conducted to explore the effect of ultrasound (US)-mediated destruction of poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) expressing nerve growth factor (NGF) (NGF/PLGA NBs) on nerve regeneration in rats following SCI. Materials and methods Adult male Sprague Dawley rats were randomly divided into four treatment groups after Allen hit models of SCI were established. The groups were normal saline (NS) group, NGF and NBs group, NGF and US group, and NGF/PLGA NBs and US group. Histological changes after SCI were observed by hematoxylin and eosin staining. Neuron viability was determined by Nissl staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to examine cell apoptosis. NGF gene and protein expressions were detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Green fluorescent protein expression in the spinal cord was examined using an inverted fluorescence microscope. The recovery of neural function was determined using the Basso, Beattie, and Bresnahan test. Results NGF therapy using US-mediated NGF/PLGA NBs destruction significantly increased NGF expression, attenuated histological injury, decreased neuron loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in rats with SCI. Conclusion US-mediated NGF/PLGA NBs destruction effectively transfects the NGF gene into target tissues and has a significant effect on the injured spinal cord. The combination of US irradiation and gene therapy through NGF/PLGA NBs holds great promise for the future of nanomedicine and the development of noninvasive treatment options for SCI and other diseases. PMID:28280337

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... Ultrasound - Pelvis Ultrasound imaging of the pelvis uses sound waves to produce pictures of the structures and ... pictures of the inside of the body using sound waves. Ultrasound imaging, also called ultrasound scanning or ...

Prostate Ultrasound

Medline Plus

Full Text Available ... ultrasound or with a rectal examination, an ultrasound-guided biopsy can be performed. This procedure involves advancing ... of the Prostate) Prostate Cancer Ultrasound- and MRI-Guided Prostate Biopsy Images related to Ultrasound - Prostate Sponsored ...

Prostate Ultrasound

Medline Plus

Full Text Available ... Z Ultrasound - Prostate Ultrasound of the prostate uses sound waves to produce pictures of a man’s prostate ... pictures of the inside of the body using sound waves. Ultrasound imaging, also called ultrasound scanning or ...

Ultrasound -- Pelvis

Science.gov (United States)

... endometrial polyps fibroids cancer, especially in patients with abnormal uterine bleeding Some physicians also use 3-D ultrasound or ... Obstetric Ultrasound Ultrasound - Prostate Kidney and Bladder Stones Abnormal Vaginal Bleeding Ovarian Cancer Images related to Ultrasound - Pelvis Sponsored ...

Development of matrix type transdermal patches of lercanidipine hydrochloride: physicochemical and in-vitro characterization

Directory of Open Access Journals (Sweden)

T Mamatha

2010-03-01

Full Text Available Background and the purpose of the study: Lercanidipine hydrochloride (LRDP is used in the treatment of hypertension because of its selectivity and specificity on the smooth vascular cells. The pharmacokinetic parameters make LRDP a suitable candidate for transdermal delivery. The purpose of the study was to select a suitable formulation for the development of transdermal drug-delivery system (TDDS of LRDP and to determine the effect of penetration enhancer, limonene on drug permeation. Methods: The matrix type TDDS of LRDP were prepared by solvent evaporation technique. Formulations A1, A2, A3, A4, A5 and A6 were composed of Eudragit RL100 (ERL and hydroxypropyl methyl cellulose (HPMC in 1.5:8.5, 3:7, 4:6, 6:4, 7:3 and 8.5:1.5 ratios respectively. All the six formulations carried 10 mg of LRDP/patch area, 8 % v/w of d-limonene as a penetration enhancer, 20 % v/w of propylene glycol as plasticizer in methanol and dichloromethane as solvent system. The prepared TDDS were evaluated for physicochemical characteristics, in-vitro release, ex-vivo permeation and skin irritation. The ex-vivo permeation studies were carried out across excised rat skin using Franz diffusion cell. Results: All the formulations exhibited satisfactory physicochemical characteristics. Cumulative percentage of the drug released in 24 hrs from the six formulations were 82.0 %, 74.9 %, 63.2 %, 63.5 %, 59.8 % and 53.5 % respectively. Corresponding values for the cumulative amounts of the drug permeated across the rat skin for the above matrix films were 2644.5, 2347.2, 2249.5, 1933.4, 2021.5 and 1663.4 µg/cm2 respectively. By fitting the data into zero order, first order and Higuchi model, it was concluded that drug release from matrix films followed Higuchi model and the mechanism of the drug release was diffusion mediated. The patches were seemingly free of potentially hazardous skin irritation.  Conclusions: The patches composed of ERL, HPMC (1.5:8.5 with 8 % v/w limonene as

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... endometrial polyps fibroids cancer, especially in patients with abnormal uterine bleeding Some physicians also use 3-D ultrasound or ... Obstetric Ultrasound Ultrasound - Prostate Kidney and Bladder Stones Abnormal Vaginal Bleeding Ovarian Cancer Images related to Ultrasound - Pelvis Sponsored ...

The efficacy and safety of a novel lipophilic formulation of methimazole for the once daily transdermal treatment of cats with hyperthyroidism.

Science.gov (United States)

Hill, K E; Gieseg, M A; Kingsbury, D; Lopez-Villalobos, N; Bridges, J; Chambers, P

2011-01-01

Previous studies on transdermal methimazole have used pluronic lecithin organogel as the vehicle. This might not be the most suitable vehicle for a lipophilic drug, such as methimazole. Once daily transdermal administration of a novel lipophilic formulation of methimazole is as safe and effective as oral carbimazole in treating hyperthyroidism in cats. Forty-five client-owned cats diagnosed with hyperthyroidism. Prospective study. Cats with newly diagnosed, untreated hyperthyroidism were treated with carbimazole (5 mg p.o., q12h) or methimazole (10 mg) applied to the inner pinnae q24h. Cats were examined after 0, 1, 4, 8, and 12 weeks of treatment. Clinical signs, body weight, systolic blood pressure, hematologic, serum biochemical and urine parameters, total serum thyroxine concentrations (TT4), and serum methimazole concentrations were recorded. No significant differences between groups were detected at day 0. Both formulations were effective in treating hyperthyroidism. No significant differences were detected in thyroxine concentrations, body weight, blood pressure, heart rate, alkaline phosphatase, alanine aminotransferase, creatinine, urea, and urine specific gravity (USG) between groups. The serum methimazole concentrations correlated poorly with TT4-concentrations in both groups. In this 12-week trial, once daily application of a novel formulation of transdermal methimazole applied to the pinnae was as effective and safe as twice daily oral carbimazole in the treatment of cats with hyperthyroidism. This novel formulation and transdermal application could have practical advantages to some pet owners. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Treatment with subcutaneous and transdermal fentanyl: Results from a population pharmacokinetic study in cancer patients

NARCIS (Netherlands)

A.W. Oosten (Astrid); J.A. Abrantes (João A.); S. Jönsson (Siv); P. de Bruijn (Peter); E.J.M. Kuip (Evelien); A. Falcão (Amílcar); C.C.D. van der Rijt (Carin); A.H.J. Mathijssen (Ron)

2016-01-01

textabstractPurpose: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we

A Transdermal Drug Delivery System Based on LIGA Technology and Soft Lithography

Science.gov (United States)

Matteucci, Marco; Perennes, Frederic; Marmiroli, Benedetta; Di Fabrizio, Enzo

2007-01-01

This report presents a transdermal drug delivery system based on LIGA fabricated microparts. It is a portable device combining a magnetically actuated micro gear pump with a microneedle array. The fluidic behaviour of the system is analyzed in order to predict its performance according to the dimension of the microparts and then compared to experimental data. The manufacturing process of both micropump and microneedle array are described.

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... Radiation Therapy for Gynecologic Cancers Radiation Therapy for Prostate Cancer top of page This page was reviewed on ... Abdomen Children's (Pediatric) Ultrasound - Abdomen Obstetric Ultrasound Ultrasound - Prostate Kidney and Bladder Stones Abnormal Vaginal Bleeding ... Images related to Ultrasound - Pelvis Sponsored by Please ...

MRI-Guided Focused Ultrasound as a New Method of Drug Delivery

Directory of Open Access Journals (Sweden)

M. Thanou

2013-01-01

Full Text Available Ultrasound-mediated drug delivery under the guidance of an imaging modality can improve drug disposition and achieve site-specific drug delivery. The term focal drug delivery has been introduced to describe the focal targeting of drugs in tissues with the help of imaging and focused ultrasound. Focal drug delivery aims to improve the therapeutic profile of drugs by improving their specificity and their permeation in defined areas. Focused-ultrasound- (FUS- mediated drug delivery has been applied with various molecules to improve their local distribution in tissues. FUS is applied with the aid of microbubbles to enhance the permeability of bioactive molecules across BBB and improve drug distribution in the brain. Recently, FUS has been utilised in combination with MRI-labelled liposomes that respond to temperature increase. This strategy aims to “activate” nanoparticles to release their cargo locally when triggered by hyperthermia induced by FUS. MRI-guided FUS drug delivery provides the opportunity to improve drug bioavailability locally and therefore improve the therapeutic profiles of drugs. This drug delivery strategy can be directly translated to clinic as MRg FUS is a promising clinically therapeutic approach. However, more basic research is required to understand the physiological mechanism of FUS-enhanced drug delivery.

Treatment with subcutaneous and transdermal fentanyl: results from a population pharmacokinetic study in cancer patients

NARCIS (Netherlands)

Oosten, A.W.; Abrantes, J.A.; Jonsson, S.; Bruijn, P. de; Kuip, E.J.M.; Falcao, A.; Rijt, C.C. van der; Mathijssen, R.H.

2016-01-01

PURPOSE: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the

Transdermal rivastigmine for HIV-associated cognitive impairment: A randomized pilot study.

Directory of Open Access Journals (Sweden)

Jose A Muñoz-Moreno

Full Text Available To assess the efficacy and safety of transdermal rivastigmine for the treatment of HIV-associated cognitive impairment.We recruited HIV-infected patients with cognitive impairment on stable antiretroviral therapy in a randomized controlled pilot trial with a 48-week follow-up. An additional assessment was held at 12 weeks. Participants received transdermal rivastigmine (9.5 mg daily, lithium (400 mg twice daily, titrated progressively, or remained in a control group (no new medication. The primary efficacy endpoint was change in a global cognitive score (NPZ-7. Secondary endpoints included change in specific cognitive measures, domains, and functional parameters. Safety covered the frequency of adverse events and changes in laboratory results.Seventy-six subjects were screened, and 29 were finally enrolled. Better cognitive outcomes were observed in all groups, although there were no significant differences between the arms (mean NPZ-7 change [SD]: rivastigmine, 0.35 (0.14; lithium, 0.25 (0.40; control, 0.20 (0.44 (p = 0.78. The rivastigmine group showed the highest positive trend (mean NPZ-7 [SD], baseline vs week 48: rivastigmine, -0.47 (0.22 vs -0.11 (0.29, p = 0.06; lithium, -0.50 (0.40 vs -0.26 (0.21, p = 0.22; control, -0.52 (0.34 vs -0.32 (0.52, p = 0.44. The cognitive domains with the highest positive trends were information processing speed at week 12 and executive function at week 48 (rivastigmine vs control: information processing speed, 0.35 (0.64 vs -0.13 (0.25, p = 0.17, d = 0.96; and executive functioning, 0.73 (0.33 vs 0.03 (0.74, p = 0.09, d = 1.18. No relevant changes were observed regarding functional outcomes. A total of 12 (41% individuals dropped out of the study: 2 (20% were due to medication-related effects in the rivastigmine group and 4 (36% in the lithium group. No severe adverse events were reported.The results from this small randomized trial indicate that transdermal rivastigmine did not provide significant

Aptamer-conjugated and drug-loaded acoustic droplets for ultrasound theranosis.

Science.gov (United States)

Wang, Chung-Hsin; Kang, Shih-Tsung; Lee, Ya-Hsuan; Luo, Yun-Ling; Huang, Yu-Fen; Yeh, Chih-Kuang

2012-02-01

Tumor therapy requires multi-functional treatment strategies with specific targeting of therapeutics to reduce general toxicity and increase efficacy. In this study we fabricated and functionally tested aptamer-conjugated and doxorubicin (DOX)-loaded acoustic droplets comprising cores of liquid perfluoropentane compound and lipid-based shell materials. Conjugation of sgc8c aptamers provided the ability to specifically target CCRF-CEM cells for both imaging and therapy. High-intensity focused ultrasound (HIFU) was introduced to trigger targeted acoustic droplet vaporization (ADV) which resulted in both mechanical cancer cell destruction by inertial cavitation and chemical treatment through localized drug release. HIFU insonation showed a 56.8% decrease in cell viability with aptamer-conjugated droplets, representing a 4.5-fold increase in comparison to non-conjugated droplets. In addition, the fully-vaporized droplets resulted in the highest DOX uptake by cancer cells, compared to non-vaporized or partially vaporized droplets. Optical studies clearly illustrated the transient changes that occurred upon ADV of droplet-targeted CEM cells, and B-mode ultrasound imaging revealed contrast enhancement by ADV in ultrasound images. In conclusion, our fabricated droplets functioned as a hybrid chemical and mechanical strategy for the specific destruction of cancer cells upon ultrasound-mediated ADV, while simultaneously providing ultrasound imaging capability. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effect of microemulsions on transdermal delivery of citalopram: optimization studies using mixture design and response surface methodology

Directory of Open Access Journals (Sweden)

Huang CT

2013-06-01

Full Text Available Chi-Te Huang,1 Ming-Jun Tsai,2,3 Yu-Hsuan Lin,1 Yaw-Sya Fu,4 Yaw-Bin Huang,5 Yi-Hung Tsai,5 Pao-Chu Wu11School of Pharmacy, Kaohsiung Medical University, Kaohsiung City, 2Department of Neurology, China Medical University Hospital, Taichung, 3School of Medicine, Medical College, China Medical University, Taichung, 4Faculty of Biomedical Science and Environmental Biology, 5Graduate Institute of Clinical Pharmacy, Kaohsiung Medical University, Kaohsiung City, Taiwan, Republic of ChinaAbstract: The aim of this study was to evaluate the potential of microemulsions as a drug vehicle for transdermal delivery of citalopram. A computerized statistical technique of response surface methodology with mixture design was used to investigate and optimize the influence of the formulation compositions including a mixture of Brij 30/Brij 35 surfactants (at a ratio of 4:1, 20%–30%, isopropyl alcohol (20%–30%, and distilled water (40%–50% on the properties of the drug-loaded microemulsions, including permeation rate (flux and lag time. When microemulsions were used as a vehicle, the drug permeation rate increased significantly and the lag time shortened significantly when compared with the aqueous control of 40% isopropyl alcohol solution containing 3% citalopram, demonstrating that microemulsions are a promising vehicle for transdermal application. With regard to the pharmacokinetic parameters of citalopram, the flux required for the transdermal delivery system was about 1280 µg per hour. The microemulsions loaded with citalopram 3% and 10% showed respective flux rates of 179.6 µg/cm2 and 513.8 µg/cm2 per hour, indicating that the study formulation could provide effective therapeutic concentrations over a practical application area. The animal study showed that the optimized formulation (F15 containing 3% citalopram with an application area of 3.46 cm2 is able to reach a minimum effective therapeutic concentration with no erythematous reaction

Nanostructured lipid carriers for transdermal delivery of acid labile lansoprazole.

Science.gov (United States)

Lin, Wen Jen; Duh, Yi Shein

2016-11-01

The aim of this study was to develop nanostructured lipid carriers (NLCs) for transdermal delivery of acid-labile lansoprazole (LPZ). The drug loading, particle size, zeta potential, thermal behavior and stability of NLCs were evaluated. The particle size of NLCs was in the range of 90-210nm and the zeta potential was -61.9 to +3.2mV dependent of the compositions. Stearylamine (SA) prevented lansoprazole degradation and maintained drug stable in NLCs. The anionic sodium dodecyl sulfate (SDS) adsorbed on the lipid surface and formed complex with cationic SA to prevent NLCs aggregation. The effects of type (e.g., isopropyl myristate (IPM), menthol) and concentration (e.g., 1.25, 2.50, 3.75%w/w) of enhancers on penetration of lansoprazole NLC hydrogels were investigated in vitro using Wistar rat skin. The steady-state flux of lansoprazole NLC hydrogel containing 3.75% IPM was the highest which was enhanced by 2.7 folds as compared to enhancer-free NLC hydrogel. In vivo pharmacokinetics of lansoprazole following transdermal delivery of NLC hydrogel showed that the elimination of drug was significantly reduced and the mean residence time of drug was prominently prolonged as compared to intravenous drug solution (p<0.005). The accumulation of drug in the skin and continuous penetration of drug through the skin accounted for the maintenance of drug concentration for at least 24h. Copyright © 2016 Elsevier B.V. All rights reserved.

A new once-a-day fentanyl citrate patch (Fentos Tape) could be a new treatment option in patients with end-of-dose failure using a 72-h transdermal fentanyl matrix patch.

Science.gov (United States)

Koike, Kazuhiko; Terui, Takeshi; Nagasako, Tomokazu; Horiuchi, Iori; Machino, Takayuki; Kusakabe, Toshiro; Hirayama, Yasuo; Mihara, Hiroyoshi; Yamakage, Michiaki; Kato, Junji; Nishisato, Takuji; Ishitani, Kunihiko

2016-03-01

The recommended dosing interval for transdermal fentanyl is every 72 h. However, some patients will have "end-of-dose failure," which may be seen as an increase of episodes of severe pain flares at the third day after application of the patch. A new once-a-day fentanyl patch was developed in Japan since 2010. This study aimed to assess the efficacy of the once-a-day fentanyl citrate patch for patients with cancer-related pain receiving the 72-h transdermal fentanyl not lasting 72 h. We performed a cross-sectional retrospective analysis of 445 inpatients with the 72-h transdermal fentanyl at Higashi Sapporo Hospital. We could switch to the once-a-day fentanyl citrate patch if patients reported inadequate pain relief beyond 48 h after application of the 72-h transdermal fentanyl. Patients recorded baseline scores for background pain intensity (PI) and the frequency of use of daily rescue medication for breakthrough cancer pain (BTcP). Of all patients, 10.1% showed the increase in PI of 30% or more baseline PI on the third day after application of the 72-h transdermal fentanyl. Of patients, 84.4% were converted from equivalent dose of the 72-h transdermal fentanyl to the once-a-day fentanyl citrate patch. On the third day after switching, 60.5% of patients showed a reduction of more than 30% from baseline PI. Switching to the once-a-day fentanyl citrate patch significantly reduced the mean frequency of daily rescue dose for BTcP. A once-a-day fentanyl citrate patch provided stable pain control. Its use may be considered as the dominant strategy for patients receiving a 72-h transdermal fentanyl not lasting 72 h.

Transdermal Delivery and Cutaneous Targeting of Antivirals using a Penetration Enhancer and Lysolipid Prodrugs

Czech Academy of Sciences Publication Activity Database

Diblíková, D.; Kopečná, M.; Školová, B.; Krečmerová, Marcela; Roh, J.; Hrabálek, A.; Vávrová, K.

2014-01-01

Roč. 31, č. 4 (2014), s. 1071-1081 ISSN 0724-8741 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonate antivirals * lysolipid prodrug * penetration enhancer * skin absorption * transdermal drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 3.420, year: 2014

General Ultrasound Imaging

Medline Plus

Full Text Available ... inserted into a man's rectum to view the prostate. Transvaginal ultrasound. The transducer is inserted into a ... Stenting Ultrasound-Guided Breast Biopsy Obstetric Ultrasound Ultrasound - Prostate Biopsies - Overview Images related to General Ultrasound Videos ...

General Ultrasound Imaging

Medline Plus

Full Text Available ... News Physician Resources Professions Site Index A-Z General Ultrasound Ultrasound imaging uses sound waves to produce ... the limitations of General Ultrasound Imaging? What is General Ultrasound Imaging? Ultrasound is safe and painless, and ...

Transdermal uptake of diethyl phthalate and di(n-butyl) phthalate directly from air: Experimental verification

DEFF Research Database (Denmark)

Weschler, Charles J.; Bekö, Gabriel; Koch, Holger M.

2015-01-01

of phthalate esters. Objectives: This study investigated transdermal uptake, directly from air, of diethyl phthalate (DEP) and di(n-butyl) phthalate (DnBP) in humans. Methods: In a series of experiments, six human participants were exposed for 6 hr in a chamber containing deliberately elevated air...

Genetic, pathological and physiological determinants of transdermal fentanyl pharmacokinetics in 620 cancer patients of the EPOS study

DEFF Research Database (Denmark)

Barratt, Daniel T; Bandak, Benedikte; Klepstad, Pål

2014-01-01

This study aimed to investigate whether CYP3A4/5 genetic variants, together with clinical and patient factors, influence serum fentanyl and norfentanyl concentrations and their ratio in cancer pain patients receiving transdermal fentanyl....

Synergistic effect of iontophoresis and chemical enhancers on transdermal permeation of tolterodine tartrate for the treatment of overactive bladder

Directory of Open Access Journals (Sweden)

D. Prasanthi

2013-01-01

Full Text Available Purpose The objective of the study was to evaluate the synergistic transdermal permeation effect of chemical enhancers and iontophoresis technique on tolterodine tartrate (TT transdermal gel and to evaluate its pharmacokinetic properties. Materials and Methods Taguchi robust design was used for optimization of formulations. Skin permeation rates were evaluated using the Keshary-chein type diffusion cells in order to optimize the gel formulation. In-vivo studies of the optimized formulation were performed in a rabbit model and histopathology studies of optimized formulation were performed on rats. Results Transdermal gels were formulated successfully using Taguchi robust design method. The type of penetration enhancer, concentration of penetration enhancer, current density and pulse on/off ratio were chosen as independent variables. Type of penetration enhancer was found to be the significant factor for all the responses. Permeation parameters were evaluated when maximum cumulative amount permeated in 24 hours (Q24 was 145.71 ± 2.00µg/cm2 by CIT4 formulation over control (91.89 ± 2.30µg/cm2. Permeation was enhanced by 1.75 fold by CIT4 formulation. Formulation CIT4 containing nerolidol (5% and iontophoretic variables applied (0.5mA/cm2 and pulse on/off ratio 3:1 was optimized. In vivo studies with optimized formulation CIT4 showed increase in AUC and T1/2 when compared to oral suspension in rabbits. The histological studies showed changes in dermis indicating the effect of penetration enhancers and as iontophoresis was continued only for two cycles in periodic fashion so it did not cause any skin damage observed in the slides. Conclusion Results indicated that iontophoresis in combination with chemical enhancers is an effective method for transdermal administration of TT in the treatment of overactive bladder.

Prostate Ultrasound

Medline Plus

Full Text Available ... through blood vessels. Ultrasound imaging is a noninvasive medical test that helps physicians diagnose and treat medical conditions. Prostate ultrasound, also called transrectal ultrasound, provides ...

An experimental trial exploring the impact of continuous transdermal alcohol monitoring upon alcohol consumption in a cohort of male students.

Science.gov (United States)

Neville, Fergus G; Williams, Damien J; Goodall, Christine A; Murer, Jeffrey S; Donnelly, Peter D

2013-01-01

To examine the impact of continuous transdermal alcohol monitoring upon alcohol consumption in male students at a Scottish university. Using a within-subject mixed-methods design, 60 male university students were randomly allocated into three experimental conditions using AUDIT score stratified sampling. Participants in Conditions A and B were asked not to consume alcohol for a 14-day period, with those in Condition A additionally being required to wear a continuous transdermal alcohol monitoring anklet. Condition C participants wore an anklet and were asked to continue consuming alcohol as normal. Alcohol consumption was measured through alcohol timeline follow-back, and using data collected from the anklets where available. Diaries and focus groups explored participants' experiences of the trial. Alcohol consumption during the 14-day trial decreased significantly for participants in Conditions A and B, but not in C. There was no significant relative difference in units of alcohol consumed between Conditions A and B, but significantly fewer participants in Condition A drank alcohol than in Condition B. Possible reasons for this difference identified from the focus groups and diaries included the anklet acting as a reminder of commitment to the study (and the agreement to sobriety), participants feeling under surveillance, and the use of the anklet as a tool to resist social pressure to consume alcohol. The study provided experience in using continuous transdermal alcohol monitors in an experimental context, and demonstrated ways in which the technology may be supportive in facilitating sobriety. Results from the study have been used to design a research project using continuous transdermal alcohol monitors with ex-offenders who recognise a link between their alcohol consumption and offending behaviour.

Solid Microneedles for Transdermal Delivery of Amantadine Hydrochloride and Pramipexole Dihydrochloride

Directory of Open Access Journals (Sweden)

Mylien T. Hoang

2015-09-01

Full Text Available The aim of this project was to study the influence of microneedles on transdermal delivery of amantadine hydrochloride and pramipexole dihydrochloride across porcine ear skin in vitro. Microchannel visualization studies were carried out and characterization of the microchannel depth was performed using confocal laser scanning microscopy (CLSM to demonstrate microchannel formation following microneedle roller application. We also report, for the first time, the use of TA.XT Plus Texture Analyzer to characterize burst force in pig skin for transdermal drug delivery experiments. This is the force required to rupture pig skin. The mean passive flux of amantadine hydrochloride, determined using a developed LC–MS/MS technique, was 22.38 ± 4.73 µg/cm2/h, while the mean flux following the use of a stainless steel microneedle roller was 49.04 ± 19.77 µg/cm2/h. The mean passive flux of pramipexole dihydrochloride was 134.83 ± 13.66 µg/cm2/h, while the flux following the use of a stainless steel microneedle roller was 134.04 ± 0.98 µg/cm2/h. For both drugs, the difference in flux values following the use of solid stainless steel microneedle roller was not statistically significantly (p > 0.05. Statistical analysis was carried out using the Mann–Whitney Rank sum test.

Increased skin permeation efficiency of imperatorin via charged ultradeformable lipid vesicles for transdermal delivery

Directory of Open Access Journals (Sweden)

Lin HW

2018-02-01

Full Text Available Hongwei Lin,1,2 Qingchun Xie,1,2 Xin Huang,1,2 Junfeng Ban,1,2 Bo Wang,1,2 Xing Wei,3 Yanzhong Chen,1,2 Zhufen Lu1,2 1Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3Guangdong Shennong Chinese Medicine Research Institute, Guangzhou, People’s Republic of China Aim: The aim of this work was to develop a novel vesicular carrier, ultradeformable liposomes (UDLs, to expand the applications of the Chinese herbal medicine, imperatorin (IMP, and increase its transdermal delivery. Methods: In this study, we prepared IMP-loaded UDLs using the thin-film hydration method and evaluated their encapsulation efficiency, vesicle deformability, skin permeation, and the amounts accumulated in different depths of the skin in vitro. The influence of different charged surfactants on the properties of the UDLs was also investigated. Results: The results showed that the UDLs containing cationic surfactants had high entrapment efficiency (60.32%±2.82%, an acceptable particle size (82.4±0.65 nm, high elasticity, and prolonged drug release. The penetration rate of IMP in cationic-UDLs was 3.45-fold greater than that of IMP suspension, which was the highest value among the vesicular carriers. UDLs modified with cationic surfactant also showed higher fluorescence intensity in deeper regions of the epidermis. Conclusion: The results of our study suggest that cationic surfactant-modified UDLs could increase the transdermal flux, prolong the release of the drug, and serve as an effective dermal delivery system for IMP. Keywords: ultradeformable liposomes, cationic, imperatorin, skin permeation, transdermal drug delivery

Effectiveness and tolerability of transdermal rivastigmine in the treatment of Alzheimer’s disease in daily practice

Directory of Open Access Journals (Sweden)

Seibert J

2012-04-01

Full Text Available Johannes Seibert1, Ferenc Tracik2,3, Konstantin Articus2, Stefan Spittler41Outpatient Clinic, Heidelberg, Germany; 2Novartis Pharma, Nürnberg, Germany; 3Department of Neurology, Heinrich-Heine University, Düsseldorf, Germany; 4Alexianer Krefeld, Maria Hilf Clinic, Krefeld, GermanyBackground: Oral cholinesterase inhibitors at doses efficacious for the treatment of Alzheimer’s disease (AD are often prematurely discontinued due to gastrointestinal side effects. In controlled clinical trials, transdermal rivastigmine demonstrated less such effects at similar efficacy. The current study aimed to verify the validity of this data in daily practice.Methods: This was a prospective, multicenter, observational study on transdermal rivastigmine in Germany. Eligible patients were those with AD who had not yet been treated with rivastigmine. Outcome measures were changes in clock-drawing test, Mini-Mental State Examination (MMSE, Caregiver Burden Scale, Clinical Global Impression (CGI, physicians’ assessments of tolerability, and the incidence of adverse events (AEs over 4 months of treatment.Results: In 257 centers 1113 patients were enrolled; 614 women and 499 men, mean age 76.5 years. In 58% of patients AD was treated for the first time and in 42% therapy was switched to transdermal rivastigmine, mostly due to lack of tolerability (13.6% or effectiveness (26.9%. After 4 months, 67.4% of patients were on the target dose of 9.5 mg/day and 21.8% were still on 4.6 mg/day. MMSE significantly improved in patients with and without pretreatment (ΔMMSE, 0.9 ± 3.4 and 0.8 ± 3.4, respectively, both P < 0.001; the CGI score improved in 60.9% and 61.3% of patients, respectively. Overall 11.7% of patients had AEs, mainly affecting the skin or the gastrointestinal tract; in 1.1% of cases AEs were serious; 14.7% of patients discontinued therapy, 6.0% due to AEs. With rivastigmine treatment the percentage of patients taking psychotropic comedication decreased

Evaluations of imidazolium ionic liquids as novel skin permeation enhancers for drug transdermal delivery.

Science.gov (United States)

Zhang, Ding; Wang, Huai-Ji; Cui, Xiu-Ming; Wang, Cheng-Xiao

2017-06-01

In this work, imidazolium ionic liquids (imidazolium ILs) were employed as the novel chemical permeation enhancers (CPEs) and their performances and mechanisms of action were deeply investigated. Testosterone was used as a model drug to investigate the transdermal delivery enhancement of twenty imdidazolium ILs. The results suggested that the promotion activity connected to the structure and composition of the ILs. The quantitative structure-activity relationship (QSAR) model revealed a good linearity between the electronic properties of ILs and their enhancements. Furthermore, the transepidermal water loss (TEWL) and scanning laser confocal microscope (CLSM) examinations showed the strong improvement of ILs on skin barrier permeability, which were well correlated with the drug penetration profiles. The total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and atomic force microscope (AFM) evaluations of skins indicated that the ILs can disrupt the regular and compact arrangements of the corneocytes, change the surface properties of stratum corneum, and make the skin structure more permeable. Our work demonstrated the significant skin permeation promotion profiles of the imidazolium ILs, which are of great potential in transdermal drug delivery systems.

Determination of two capsaicinoids in analgesic transdermal patches using RP-HPLC and UV spectroscopy

Directory of Open Access Journals (Sweden)

F. Kobarfard

2017-11-01

Full Text Available Background and objectives: At the present time, a considerable frontier in the administration of therapeutic medications is transdermal drug delivery. Methods: In this study, a rapid, precise, sensitive and selective reversed-phasehigh performance liquid chromatography (RP-HPLC method has been evaluated, developed and validated to separate and quantitate capsaicin and dihydrocapsaicin (main active agents in analgesic dermal patches produced in Iran. Results: After isolation from laminated adhesive patches, capsaicinoids were analyzed on Lichrospher C18 analytical columns with reversed phase, using a mobile phase composition of methanol and distilled water (70:30 v/v and without any buffer (pH=6.5. The flow rate was 1 mL/min and the UV detector was operating at 281 nm. The assay was found to be linear over the range of 0.1-1.0 mg/mL. All validation parameters were within the acceptable range. Conclusion: It seems that the developed method was fairly sensitive and reliable in measuring capsaicinoids in commercially available analgesic transdermal patches in Iran.

Inefficacy of high-dose transdermal fentanyl in a patient with neuropathic pain, a case report.

NARCIS (Netherlands)

Bleeker, C.P.; Bremer, R.; Dongelmans, D.A.; Dongen, R.T.M. van; Crul, B.J.P.

2001-01-01

Pain partially responsive to opioids can lead to rapid escalating dosages due to tolerance development. In this report the case of a 58-year-old female with neuropathic pain using increasing transdermal (TTS) fentanyl dosages to a maximum dose of 3400 microg/h resulting in fentanyl plasma levels of

Dodecyl Amino Glucoside Enhances Transdermal and Topical Drug Delivery via Reversible Interaction with Skin Barrier Lipids

Czech Academy of Sciences Publication Activity Database

Kopečná, M.; Macháček, M.; Prchalová, Eva; Štěpánek, P.; Drašar, P.; Kotora, Martin; Vávrová, K.

2017-01-01

Roč. 34, č. 3 (2017), s. 640-653 ISSN 0724-8741 Institutional support: RVO:61388963 Keywords : penetration enhancers * sugar * topical drug delivery * transdermal drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Pharmacology and pharmacy Impact factor: 3.002, year: 2016

A Novel Transdermal Power Transfer Device for the Application of Implantable Microsystems

Directory of Open Access Journals (Sweden)

Jing-Quan Liu

2015-03-01

Full Text Available This paper presents a transdermal power transfer device for the application of implantable devices or systems. The device mainly consists of plug and socket. The power transfer process can be started after inserting the plug into the socket with an applied potential on the plug. In order to improve the maneuverability and reliability of device during power transfer process, the metal net with mesh structure were added as a part of the socket to serve as intermediate electrical connection layer. The socket was encapsulated by polydimethylsiloxane (PDMS with good biocompatibility and flexibility. Two stainless steel hollow needles placed in the same plane acted as the insertion part of the needle plug, and Parylene C thin films were deposited on needles to serve as insulation layers. At last, the properties of the transdermal power transfer device were tested. The average contact resistance between needle and metal mesh was 0.454 Ω after 50 random insertions, which showed good electrical connection. After NiMH (nickel-metal hydride batteries were recharged for 10 min with current up to 200 mA, the caused resistive heat was less than 0.6 °C, which also demonstrated the low charging temperature and was suitable for charging implantable devices.

Development of Novel Formulations to Enhance in Vivo Transdermal Permeation of Tocopherol

Directory of Open Access Journals (Sweden)

Nada Aly H.

2014-09-01

Full Text Available Tocopherol represents a big challenge for transdermal permeation owing to its extreme hydrophobicity and large molecular mass. The aim of the present study was to develop alpha-tocopherol (T topical formulations and evaluate their ex vivo and in vivo permeation. Franz diffusion cells were used for ex vivo permeation, and neonatal rats were used for in vivo permeation. Seven gel formulations and 21 liquid formulations were investigated for physical stability, viscosity and permeation of T. Analysis of T was performed by a validated HPLC method using a UV detector. The ex vivo permeation from gel and emulsion formulations was very poor (0.001-0.015 %. Highest permeation was observed from monophasic liquid formulations containing dimethyl sulfoxide (DMSO, tocopheryl polyethylene glycols (TPGs, propylene glycol, ethanol and 9.5 % T. The in vivo results demonstrated higher retention in the epidermis compared to subcutaneous tissues, 1377 and 1.13 μg g-1, respectively. Increasing T concentration from 4.8 to 9.5 % did not increase the amount permeated or % of T retained. It was concluded that simple solutions of T in the presence of DMSO and TPGs were more promising systems for effective transdermal permeation compared to gel, emulsion or oleaginous systems.

Patient considerations in the use of transdermal iontophoretic fentanyl for acute postoperative pain

Directory of Open Access Journals (Sweden)

Hartrick CT

2016-04-01

Full Text Available Craig T Hartrick,1 Cecile R Pestano,1 Li Ding,2 Hassan Danesi,2 James B Jones,2 1Beaumont Health System, Troy, MI, 2The Medicines Company, Parsippany, NJ, USA Abstract: Opioids are commonly used in the management of moderate-to-severe postoperative pain. Patient-controlled analgesic techniques are recognized as preferred administration methods. Previously, research has focused on intravenously administered opioids via a programmable pump. More recently, an iontophoretic transdermal system (ITS, which is patient controlled, has been developed. The focus of this review is on pain management using the fentanyl ITS during the 24–72-hour time period immediately following surgery. Fentanyl ITS offers a needle-free alternative to traditional intravenous (IV patient-controlled analgesia (PCA system that is as effective and safe as IV PCA. This system is easy to use for both patients and nurses. The use of fentanyl ITS is generally associated with a better ease-of-care profile, including a greater ease of mobility, from a patients' perspective when compared with morphine IV PCA. Keywords: patient-controlled analgesia, fentanyl iontophoretic transdermal system, ease of care, mobility, patient perspective, review

From high doses of oral rivastigmine to transdermal rivastigmine patches: user experience and satisfaction among caregivers of patients with mild to moderate Alzheimer disease.

Science.gov (United States)

Reñé, R; Ricart, J; Hernández, B

2014-03-01

Rivastigmine, a treatment for mild to moderate Alzheimer disease (AD), is the first cholinesterase inhibitor to be available in the transdermal format. We aim to describe user experience and satisfaction with the rivastigmine patch, as well as any clinical changes perceived in patients. Observational, cross-sectional, multicentre study with 239 investigators and 1851 informal caregivers of patients with mild to moderate AD. Patients were treated with transdermal rivastigmine patches for ≥ 6 months and had previously received high doses of oral rivastigmine. Mean caregiver age was 59.8±14.4 years and 70.9% were women. They spent 10.0±7.1hours per day providing care and 79.8% lived with the patient. Patch instructions were described as easy to follow by 97.1% of the caregivers and 92.1% of them rated patch application as easy or very easy. The most commonly cited disadvantage was adhesion problems (26.8%). Discontinuation of treatment was due to cutaneous reactions in most cases. Overall, 76.5% of the caregivers were satisfied or very satisfied with transdermal treatment and 77.4% considered that its interference with daily activities was minimal or null. The patch was preferred to oral treatment by 94.3% of caregivers. Clinical Global Impression of Change ratings improved according to 61.3% of the caregivers and 53% of the investigators. Few caregivers reported medication forgetfulness. Most caregivers of patients with mild to moderate AD preferred the transdermal format of rivastigmine to the oral format. Caregivers also reported overall satisfaction, ease of use, and reduced impact on daily activities for transdermal rivastigmine format, in addition to patient improvement compared to their condition under the previous treatment. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Effects of transdermal magnesium chloride on quality of life for patients with fibromyalgia: a feasibility study.

Science.gov (United States)

Engen, Deborah J; McAllister, Samantha J; Whipple, Mary O; Cha, Stephen S; Dion, Liza J; Vincent, Ann; Bauer, Brent A; Wahner-Roedler, Dietlind L

2015-09-01

Fibromyalgia is a syndrome characterized by chronic pain, fatigue, depression, and sleep disturbances. Its primary cause is unclear. Several studies have reported decreased intracellular magnesium levels in patients with fibromyalgia and have found negative correlation between magnesium levels and fibromyalgia symptoms. To gather preliminary data on whether transdermal magnesium can improve quality of life for women who have fibromyalgia. This is a patient questionnaires and survey in a fibromyalgia clinic at a tertiary medical center. Forty female patients with the diagnosis of fibromyalgia were enrolled. Each participant was provided a spray bottle containing a transdermal magnesium chloride solution and asked to apply 4 sprays per limb twice daily for 4 weeks. Participants were asked to complete the Revised Fibromyalgia Impact Questionnaire, SF-36v2 Health Survey, and a quality-of-life analog scale at baseline, week 2, and week 4. Questionnaire and survey scores, evaluated through intent-to-treat and per-protocol analyses. Twenty-four patients completed the study (mean [SD] age, 57.2 [7.6] years; white, 95%; mean body mass index, 31.3 kg/m2). With intention-to-treat analysis, Revised Fibromyalgia Impact Questionnaire subscale and total scores were significantly improved at week 2 and week 4 (total score, P=0.001). Per-protocol analysis results were similar: all subscales of the Revised Fibromyalgia Impact Questionnaire were significantly improved at week 2 and week 4 (total score, P=0.001). This pilot study suggests that transdermal magnesium chloride applied on upper and lower limbs may be beneficial to patients with fibromyalgia. ClinicalTrials.gov.ldentifier NCT01968772.

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... three types of pelvic ultrasound: abdominal, vaginal (for women), and rectal (for men). These exams are frequently ... pelvic ultrasound: abdominal ( transabdominal ) vaginal ( transvaginal / endovaginal ) for women rectal ( transrectal ) for men A Doppler ultrasound exam ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... a pelvic ultrasound examination. Doppler ultrasound , also called color Doppler ultrasonography, is a special ultrasound technique that ... and processes the sounds and creates graphs or color pictures that represent the flow of blood through ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... Ultrasound imaging is a noninvasive medical test that helps physicians diagnose and treat medical conditions. There are ... Ultrasound page for more information . Ultrasound examinations can help diagnose symptoms experienced by women such as: pelvic ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... ultrasound images are captured in real-time, they can show the structure and movement of the body's ... Obstetrical Ultrasound page for more information . Ultrasound examinations can help diagnose symptoms experienced by women such as: ...

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

Directory of Open Access Journals (Sweden)

Sutton JT

2014-10-01

Full Text Available JT Sutton,1 JL Raymond,1 MC Verleye,2 GJ Pyne-Geithman,3 CK Holland4 1University of Cincinnati, Biomedical Engineering Program, Cincinnati, OH, 2University of Notre Dame Department of Chemical Engineering, Notre Dame, IN, 3University of Cincinnati, College of Medicine, Department of Neurosurgery and the University of Cincinnati Neuroscience Institute, and Mayfield Clinic, Cincinnati, OH, 4University of Cincinnati, College of Medicine, Internal Medicine, Division of Cardiovascular Diseases, Cincinnati, OH, USA Abstract: Ultrasound-mediated drug delivery is a novel technique for enhancing the penetration of drugs into diseased tissue beds noninvasively. By encapsulating drugs into microsized and nanosized liposomes, the therapeutic can be shielded from degradation within the vasculature until delivery to a target site by ultrasound exposure. Traditional in vitro or ex vivo techniques to quantify this delivery profile include optical approaches, cell culture, and electrophysiology. Here, we demonstrate an approach to characterize the degree of nitric oxide (NO delivery to porcine carotid tissue by direct measurement of ex vivo vascular tone. An ex vivo perfusion model was adapted to assess ultrasound-mediated delivery of NO. This potent vasodilator was coencapsulated with inert octafluoropropane gas to produce acoustically active bubble liposomes. Porcine carotid arteries were excised post mortem and mounted in a physiologic buffer solution. Vascular tone was assessed in real time by coupling the artery to an isometric force transducer. NO-loaded bubble liposomes were infused into the lumen of the artery, which was exposed to 1 MHz pulsed ultrasound at a peak-to-peak acoustic pressure amplitude of 0.34 MPa. Acoustic cavitation emissions were monitored passively. Changes in vascular tone were measured and compared with control and sham NO bubble liposome exposures. Our results demonstrate that ultrasound-triggered NO release from bubble liposomes

Design, formulation and optimization of novel soft nano-carriers for transdermal olmesartan medoxomil delivery: In vitro characterization and in vivo pharmacokinetic assessment.

Science.gov (United States)

Kamran, Mohd; Ahad, Abdul; Aqil, Mohd; Imam, Syed Sarim; Sultana, Yasmin; Ali, Asgar

2016-05-30

Olmesartan is a hydrophobic antihypertensive drug with a short biological half-life, and low bioavailability, presents a challenge with respect to its oral administration. The objective of the work was to formulate, optimize and evaluate the transdermal potential of novel vesicular nano-invasomes, containing above anti-hypertensive agent. To achieve the above purpose, soft carriers (viz. nano-invasomes) of olmesartan with β-citronellene as potential permeation enhancer were developed and optimized using Box-Behnken design. The physicochemical characteristics e.g., vesicle size, shape, entrapment efficiency and skin permeability of the nano-invasomes formulations were evaluated. The optimized formulation was further evaluated for in vitro drug release, confocal microscopy and in vivo pharmacokinetic study. The optimum nano-invasomes formulation showed vesicles size of 83.35±3.25nm, entrapment efficiency of 65.21±2.25% and transdermal flux of 32.78±0.703 (μg/cm(2)/h) which were found in agreement with the predicted value generated by Box-Behnken design. Confocal laser microscopy of rat skin showed that optimized formulation was eventually distributed and permeated deep into the skin. The pharmacokinetic study presented that transdermal nano-invasomes formulation showed 1.15 times improvement in bioavailability of olmesartan with respect to the control formulation in Wistar rats. It was concluded that the response surfaces estimated by Design Expert(®) illustrated obvious relationship between formulation factors and response variables and nano-invasomes were found to be a proficient carrier system for transdermal delivery of olmesartan. Copyright © 2016 Elsevier B.V. All rights reserved.

General Ultrasound Imaging

Medline Plus

Full Text Available ... What are the limitations of General Ultrasound Imaging? What is General Ultrasound Imaging? Ultrasound is safe and ... be heard with every heartbeat. top of page What are some common uses of the procedure? Ultrasound ...

General Ultrasound Imaging

Medline Plus

Full Text Available ... Index A-Z General Ultrasound Ultrasound imaging uses sound waves to produce pictures of the inside of ... pictures of the inside of the body using sound waves. Ultrasound imaging, also called ultrasound scanning or ...

General Ultrasound Imaging

Medline Plus

Full Text Available ... guide biopsy of breast cancer ( see the Ultrasound-Guided Breast Biopsy page . diagnose a variety of heart ... Articles and Media Angioplasty and Vascular Stenting Ultrasound-Guided Breast Biopsy Obstetric Ultrasound Ultrasound - Prostate Biopsies - Overview ...

General Ultrasound Imaging

Medline Plus

Full Text Available ... of an ultrasound examination. Doppler ultrasound , also called color Doppler ultrasonography, is a special ultrasound technique that ... kidneys. There are three types of Doppler ultrasound: Color Doppler uses a computer to convert Doppler measurements ...

General Ultrasound Imaging

Medline Plus

Full Text Available ... those sound waves to create an image. Ultrasound examinations do not use ionizing radiation (as used in ... ultrasound study may be part of an ultrasound examination. Doppler ultrasound , also called color Doppler ultrasonography, is ...

Low dose transdermal estradiol induces breast density and heterogeneity changes comparable to those of raloxifene

DEFF Research Database (Denmark)

Nielsen, Mads; Raundahl, Jakob; Pettersen, Paola

2009-01-01

Objective: To investigate whether transdermal low dose estradiol treatment induces changes in mammographic density or heterogeneity compared to raloxifene. Secondarily, if these changes relate to changes in bone formation/resorption markers, and if these findings indicate elevation of breast canc...

Oral and transdermal DL-methylphenidate-ethanol interactions in C57BL/6J mice: potentiation of locomotor activity with oral delivery.

Science.gov (United States)

Bell, Guinevere H; Griffin, William C; Patrick, Kennerly S

2011-12-01

Many abusers of dl-methylphenidate co-abuse ethanol. The present animal study examined behavioral effects of oral or transdermal DL-methylphenidate in combination with a high, depressive dose of ethanol to model co-abuse. Locomotor activity of C57BL/6J mice was recorded for 3 h following dosing with either oral DL-methylphenidate (7.5 mg/kg) or transdermal DL-methylphenidate (Daytrana®;1/4 of a 12.5 cm(2) patch; mean dose 7.5 mg/kg), with or without oral ethanol (3 g/kg). Brains were enantiospecifically analyzed for the isomers of methylphenidate and the transesterification metabolite ethylphenidate. An otherwise depressive dose of ethanol significantly potentiated oral DL-methylphenidate induced increases in total distance traveled for the first 100 min (pbrain D-methylphenidate concentrations were significantly elevated by ethanol in both the oral (65% increase) and transdermal (88% increase) groups. The corresponding L-ethylphenidate concentrations were 10 ng/g and 130 ng/g. Stimulant induced motor activity in rodents may correlate with abuse liability. Potentiation of DL-methylphenidate motor effects by concomitant ethanol carries implications regarding increased abuse potential of DL-methylphenidate when combined with ethanol. Copyright © 2011 Elsevier Inc. All rights reserved.

Musculoskeletal ultrasound in rheumatology in Korea: targeted ultrasound initiative survey.

Science.gov (United States)

Kang, Taeyoung; Wakefield, Richard J; Emery, Paul

2016-04-01

In collaboration with the Targeted Ultrasound Initiative (TUI), to conduct the first study in Korea to investigate current practices in ultrasound use among Korean rheumatologists. We translated the TUI Global Survey into Korean and added questions to better understand the specific challenges facing rheumatologists in Korea. To target as many rheumatologists in Korea as possible, we created an on-line version of this survey, which was conducted from March to April 2013. Rheumatologists are in charge of ultrasound in many Korean hospitals. Rheumatologists in hospitals and private clinics use ultrasound to examine between one and five patients daily; they use ultrasound for diagnosis more than monitoring and receive compensation of about US$30-50 per patient. There are marked differences in the rates of ultrasound usage between rheumatologists who work in private practice compared with tertiary hospitals. Korean rheumatologists not currently using ultrasound in their practice appear eager to do so. This survey provides important insights into the current status of ultrasound in rheumatology in Korea and highlights several priorities; specifically, greater provision of formal training, standardization of reporting and accrual of greater experience among ultrasound users. If these needs are addressed, all rheumatology departments in Korea are likely to use ultrasound or have access to it in the future. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

A new approach for noninvasive transdermal determination of blood uric acid levels

Directory of Open Access Journals (Sweden)

Ching CTS

2014-06-01

Full Text Available Congo Tak-Shing Ching,1,2 Kok-Khun Yong,3 Yan-Dong Yao,4 Huan-Ting Shen,3 Shiu-Man Hsieh,5 Deng-Yun Jheng,1 Tai-Ping Sun,1,6 Hsiu-Li Shieh11Department of Electrical Engineering, National Chi Nan University, Nantou, 2Department of Photonics and Communication Engineering, Asia University, Taichung, 3Department of Internal Medicine, Puli Christian Hospital, Nantou, People’s Republic of China; 4Division of Science and Technology, Hong Kong Community College, Hong Kong; 5Department of Orthopedic Surgery, Puli Christian Hospital, 6Department of Electronic Engineering, Nan Kai University of Technology, Nantou, People’s Republic of ChinaAbstract: The aims of this study were to investigate the most effective combination of physical forces from laser, electroporation, and reverse iontophoresis for noninvasive transdermal extraction of uric acid, and to develop a highly sensitive uric acid biosensor (UAB for quantifying the uric acid extracted. It is believed that the combination of these physical forces has additional benefits for extraction of molecules other than uric acid from human skin. A diffusion cell with porcine skin was used to investigate the most effective combination of these physical forces. UABs coated with ZnO2 nanoparticles and constructed in an array configuration were developed in this study. The results showed that a combination of laser (0.7 W, electroporation (100 V/cm2, and reverse iontophoresis (0.5 mA/cm2 was the most effective and significantly enhanced transdermal extraction of uric acid. A custom-designed UAB coated with ZnO2 nanoparticles and constructed in a 1×3 array configuration (UAB-1×3-ZnO2 demonstrated enough sensitivity (9.4 µA/mM for quantifying uric acid extracted by the combined physical forces of laser, electroporation, and RI. A good linear relationship (R2=0.894 was demonstrated to exist between the concentration of uric acid (0.2–0.8 mM inside the diffusion cell and the current response of the

The Efficacy and Tolerability of the Clonidine Transdermal Patch in the Treatment for Children with Tic Disorders: A Prospective, Open, Single-Group, Self-Controlled Study.

Science.gov (United States)

Song, Pan-Pan; Jiang, Li; Li, Xiu-Juan; Hong, Si-Qi; Li, Shuang-Zi; Hu, Yue

2017-01-01

To evaluate the efficacy and tolerability of a clonidine transdermal patch in the treatment of children with tic disorders (TD) and to establish a predictive model for patients. Forty-one patients who met the inclusion criteria entered into 12 weeks of prospective, open, single-group, self-controlled treatment with a clonidine transdermal patch. The Yale Global Tic Severity Scale (YGTSS) was employed before therapy (baseline) and at 4, 8, and 12 weeks after therapy. (1) The total effect rates of treatment with a clonidine transdermal patch were 29.27, 53.66, and 63.41% at 4, 8, and 12 weeks, respectively. Compared with the baseline, the differences were significant at three different observation periods. (2) Compared to the level of 25% reduction, there were significant decreases in the score-reducing rate of motor tic and total tic severities at 12 weeks. (3) If the disease course was ≤24 months and the motor tic score was tic score was >16, there was an effective rate of 57.1%. If the disease course was >24 months and the clinical classification was chronic TD, there was an effective rate of 62.5%. If the disease course was >24 months and the clinical classification was Tourette's syndrome, 90% of the patients were invalid. (4) The main adverse events were rash, slight dizziness, and headache. (1) When patients were pretreated with a D2-dopamine receptor antagonist that was ineffective or not tolerated well, switching to a clonidine transdermal patch treatment was effective and safe. (2) A clonidine transdermal patch could be a first-line medication for mild and moderate TD cases that are characterized by motor tics.

Ultrasound

Science.gov (United States)

Ultrasound is a useful procedure for monitoring the baby's development in the uterus. Ultrasound uses inaudible sound waves to produce a two-dimensional image of the baby while inside the mother's ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... transducer sends out high-frequency sound waves (that the human ear cannot hear) into the body and then ... ultrasound , there are no known harmful effects on humans. top of page What are the limitations of Pelvic Ultrasound Imaging? Ultrasound waves are ...

Ultrasound-mediated Optical Imaging and Focusing in Scattering Media

Science.gov (United States)

Suzuki, Yuta

Because of its non-ionizing and molecular sensing nature, light has been an attractive tool in biomedicine. Scanning an optical focus allows not only high-resolution imaging but also manipulation and therapy. However, due to multiple photon scattering events, conventional optical focusing using an ordinary lens is limited to shallow depths of one transport mean free path (lt'), which corresponds to approximately 1 mm in human tissue. To overcome this limitation, ultrasonic modulation (or encoding ) of diffuse light inside scattering media has enabled us to develop both deep-tissue optical imaging and focusing techniques, namely, ultrasound-modulated optical tomography (UOT) and time-reversed ultrasonically encoded (TRUE) optical focusing. While UOT measures the power of the encoded light to obtain an image, TRUE focusing generates a time-reversed (or phase-conjugated) copy of the encoded light, using a phase-conjugate mirror to focus light inside scattering media beyond 1 lt'. However, despite extensive progress in both UOT and TRUE focusing, the low signal-to-noise ratio in encoded-light detection remains a challenge to meeting both the speed and depth requirements for in vivo applications. This dissertation describes technological advancements of both UOT and TRUE focusing, in terms of their signal detection sensitivities, operational depths, and operational speeds. The first part of this dissertation describes sensitivity improvements of encoded-light detection in UOT, achieved by using a large area (˜5 cm x 5 cm) photorefractive polymer. The photorefractive polymer allowed us to improve the detection etendue by more than 10 times that of previous detection schemes. It has enabled us to resolve absorbing objects embedded inside diffused media thicker than 80 lt', using moderate light power and short ultrasound pulses. The second part of this dissertation describes energy enhancement and fluorescent excitation using TRUE focusing in turbid media, using

Development of w/o microemulsion for transdermal delivery of iodide ions.

Science.gov (United States)

Lou, Hao; Qiu, Ni; Crill, Catherine; Helms, Richard; Almoazen, Hassan

2013-03-01

The objective of this study was to develop a water-in-oil (w/o) microemulsion which can be utilized as a transdermal delivery for iodide ions. Several w/o microemulsion formulations were prepared utilizing Span 20, ethanol, Capryol 90®, and water. The selected formulations had 5%, 10%, 15%, 20%, and a maximum of 23% w/w water content. Potassium iodide (KI) was incorporated in all formulations at 5% w/v. Physicochemical characterizations were conducted to evaluate the structure and stability. These studies included: mean droplet size, pH, viscosity, conductivity, and chemical stability tests. In vitro human skin permeation studies were conducted to evaluate the diffusion of the iodide ion through human skin. The w/o microemulsion formulations were stable and compatible with iodide ions with water content ranging from 5% to 23% w/w. The addition of KI influenced the physicochemical properties of microemulsion as compared to blank microemulsion formulations. In vitro human skin permeation studies indicated that selected formulations improved iodide ion diffusion significantly as compared to control (KI solution; P valuemicroemulsion. Span 20, ethanol and Capryol 90 protected the iodide ions against oxidation and formed a stable microemulsion. It is worth to note that according to Hofmeister series, iodide ions tend to lower the interfacial tension between water and oil and consequently enhance overall stability. This work illustrates that microemulsion system can be utilized as a vehicle for the transdermal administration of iodide.

Pharmacokinetics of a Transdermal Fentanyl Solution in Suffolk Sheep (Ovis aries).

Science.gov (United States)

Jen, Kimberly Y; Dyson, Melissa C; Lester, Patrick A; Nemzek, Jean A

2017-09-01

Sheep used as surgical models require appropriate pain management, and the commonly used transdermal fentanyl patches require a long predosing period to achieve adequate plasma concentrations. The aim of this study was to assess the pharmacokinetic parameters of an FDA-approved transdermal fentanyl solution (TFS) that has yet to be tested in sheep. In this study, we compared TFS at 2.7 mg/kg (n = 2), 1.7 mg/kg (n = 3), and 0.5 mg/kg (n = 3) with the control fentanyl patch at 2 μg/kg/h (n = 1); both products were applied topically to the intrascapular region. Plasma concentrations showed significant interanimal variability. Severe adverse effects occurred at both 2.7 and 1.7 mg/kg TFS and mild to moderate adverse effects were noted at 0.5 mg/kg. At all 3 doses, TFS had greater maximal concentration, clearance rate, and volume of distribution; shorter time to maximal concentration; and similar half-lives to those of the patch. In addition, we validated the use of a commercial human fentanyl ELISA kit, which positively correlated with the liquid chromatography-mass spectroscopy data, but absolute values did not match. Overall, at all 3 dosages tested (0.5, 1.7, and 2.7 mg/kg), TFS delivered fentanyl plasma concentrations that exceeded the minimal effective concentration; however, adverse effects were noted at all 3 dosages. Caution and further study are required before the use of TFS in sheep can be recommended fully.

A clinical study of transdermal contraceptive patch in Thai adolescence women.

Science.gov (United States)

Piyasirisilp, Rachatapon; Taneepanichskul, Surasak

2008-02-01

To study cycle control, compliance and safety of a transdermal contraceptive patch in adolescent Thai women. Fifty-eight healthy women were assigned to receive 3 cycles of contraceptive patch (ethinyl estradiol 20 microg and norelgestromin 150 microg/day). All participants aged 16-20 years were invited to participate from the family planning clinic at King Chulalongkorn Memorial Hospital. Data were collected on adverse effects, perceived advantages and disadvantages, body weight, blood pressure, patch detachments and compliance. Data were analyzed using mean, percentage and student's t-test. The participants' average age was 19.4 years, height 158.8 cm, weight 51.8 kg, BMI 20.8 Kg/m2. The most location of patch application was the abdomen and the most adverse event was breast tenderness (31.0%) followed by application site reaction, nausea vomiting and headache respectively. The breast symptom was mild in severity. The participants reported decrease in dysmenorrhea and shorter duration of bleeding. There were no significant changes in body weight and blood pressure. The improvement of their facial acne was reported. There were no pregnancies during use and the adhesion of the contraceptive patch is excellent. Partial patch detachment was reported in only 6.9%. No completed patch detachment was found. The present study found an overall positive impression of a new transdermal contraceptive patch. The good compliance and few side effects were demonstrated. The adhesive patch contraceptive was excellent.

A Preliminary Study of a Transdermal Radiofrequency Device for Body Slimming.

Science.gov (United States)

Key, Douglas J

2015-11-01

The use and potential of radiofrequency energy for tissue contracture and body contouring has been established in the literature. Maximum reduction of laxity can be achieved by simultaneously tightening surface tissue and reducing unwanted fat below by the transdermal application of heat to reach and maintain tissue temperature targets within a well-defined range, inducing collagen remodeling in skin as well as apoptosis of fat cells and creating an overall slimming effect. A novel device utilizes transcutaneous monopolar RF for body slimming in this manner, employing a thermistor feedback control mechanism to safely manage energy delivery and tissue temperature. Subjects (n=14) presenting with abdominal laxity were treated up to four times using the transcutaneous monopolar RF device at one or two zones in the abdominal region (at operator's discretion). Non-expert blinded graders rated correction on an arbitrary scale (0=no laxity, 4=maximum laxity) after choosing the order of the before-and-after photo sets. A patient satisfaction survey was also administered. The two graders correctly ordered 10 of 14 photo sets in agreement. Average rated improvement was 0.75 and 0.80 for graders 1 and 2, respectively. Patient survey results revealed average perceived tightening of 2.14 points on a 0 to 4 scale (0=lowest tightening result, 4=highest tightening), and 8 of 14 subjects would recommend treatment to others. Transdermal monopolar RF is a safe and effective modality for non-invasive body slimming.

Efficacy of transdermal nitroglycerine in idiopathic pre-term labour.

Science.gov (United States)

Shaikh, Shahida; Shaikh, Abdul Hameed; Akhter, Saleem; Isran, Basma

2012-01-01

To determine the efficacy of transdermal Nitroglycerine patch in idiopathic pre-term labour and foetomaternal outcome. This quasi-experimental study was conducted at the Obstetrics Unit-II of Shaikh Zayed Hospital for Women, Chandka Medical College, Shaheed Mohtarma Benazir Bhutto Medical University, Larkana, from Jan 1 to June 30, 2010. Sixtyfive pregnant women at 28-34 weeks of gestation were recruited after they met the selection criteria based on non-probability consecutive sampling. Initially, 73 patients were selected, but 65 of them completed the treatment, while 8 patients refused to continue. Patients diagnosed with pre-term labour were given glyceryl trinitrate (GTN) 5 mg/12 hours transdermal patch which was applied on the anterior abdominal wall. The second patch of same dose was given after 12 hours. Arrest of labour, prolongation of pregnancy in days or weeks along with side effects of the agent were monitored. Patients were followed till delivery to know the foeto-maternal outcome. Dramatic effects were seen in around 60 (92.3%), of the total patients who had felt relief from premature labour pains within the first hour and only 5 (7.6%) patients could not go beyond 24 hours, as among them 3 (4.61%) had previous uterine scar and 2 (3.07%) developed ruptured membranes after 12 hours of admission and their babies also could not survive. Mean pregnancy prolongation was 15.35 +/- 9.45 days (min: 4 max: 35), so delivery was deferred up to 48 hours, 3 to 7 days and more than 7 days in 4 (6.15%), 6 (9.23%) and 50 (76.92%) respectively. Glyceryl trinitrate, trans dermal patch is effective and safe tocolytic in idiopathic preterm labour. By prolonging pregnancy it improves neonatal outcome.

Modeling of transdermal drug delivery with a microneedle array

Science.gov (United States)

Lv, Y.-G.; Liu, J.; Gao, Y.-H.; Xu, B.

2006-11-01

Transdermal drug delivery is generally limited by the extraordinary barrier properties of the stratum corneum, the outer 10-15 µm layer of skin. A conventional needle inserted across this barrier and into deeper tissues could effectively deliver drugs. However, it would lead to infection and cause pain, thereby reducing patient compliance. In order to administer a frequent injection of insulin and other therapeutic agents more efficiently, integrated arrays with very short microneedles were recently proposed as very good candidates for painless injection or extraction. A variety of microneedle designs have thus been made available by employing the fabrication tools of the microelectronics industry and using materials such as silicon, metals, polymers and glass with feature sizes ranging from sub-micron to nanometers. At the same time, experiments were also made to test the capability of the microneedles to inject drugs into tissues. However, due to the difficulty encountered in measurement, a detailed understanding of the spatial and transient drug delivery process still remains unclear up to now. To better grasp the mechanisms involved, quantitative theoretical models were developed in this paper to simultaneously characterize the flow and drug transport, and numerical solutions were performed to predict the kinetics of dispersed drugs injected into the skin from a microneedle array. Calculations indicated that increasing the initial injection velocity and accelerating the blood circulation in skin tissue with high porosity are helpful to enhance the transdermal drug delivery. This study provides the first quantitative simulation of fluid injection through a microneedle array and drug species transport inside the skin. The modeling strategy can also possibly be extended to deal with a wider range of clinical issues such as targeted nanoparticle delivery for therapeutics or molecular imaging.

pH/Ultrasound Dual-Responsive Gas Generator for Ultrasound Imaging-Guided Therapeutic Inertial Cavitation and Sonodynamic Therapy.

Science.gov (United States)

Feng, Qianhua; Zhang, Wanxia; Yang, Xuemei; Li, Yuzhen; Hao, Yongwei; Zhang, Hongling; Hou, Lin; Zhang, Zhenzhong

2018-03-01

Herein, a pH/ultrasound dual-responsive gas generator is reported, which is based on mesoporous calcium carbonate (MCC) nanoparticles by loading sonosensitizer (hematoporphyrin monomethyl ether (HMME)) and modifying surface hyaluronic acid (HA). After pinpointing tumor regions with prominent targeting efficiency, HMME/MCC-HA decomposes instantaneously under the cotriggering of tumoral inherent acidic condition and ultrasound (US) irradiation, concurrently accompanying with CO 2 generation and HMME release with spatial/temporal resolution. Afterward, the CO 2 bubbling and bursting effect under US stimulus results in cavitation-mediated irreversible cell necrosis, as well as the blood vessel destruction to further occlude the blood supply, providing a "bystander effect." Meanwhile, reactive oxygen species generated from HMME can target the apoptotic pathways for effective sonodynamic therapy. Thus, the combination of apoptosis/necrosis with multimechanisms consequently results in a remarkable antitumor therapeutic efficacy, simultaneously minimizing the side effects on major organs. Moreover, the echogenic property of CO 2 make the nanoplatform as a powerful ultrasound contrast agent to identify cancerous lesions. Based on the above findings, such all-in-one drug delivery platform of HMME/MCC-HA is utilized to provide the US imaging guidance for therapeutic inertial cavitation and sonodynamic therapy simultaneously, which highlights possibilities of advancing cancer theranostics in biomedical fields. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Statistically optimized fast dissolving microneedle transdermal patch of meloxicam: A patient friendly approach to manage arthritis.

Science.gov (United States)

Amodwala, Sejal; Kumar, Praveen; Thakkar, Hetal P

2017-06-15

The long term administration of Meloxicam for the management of arthritis, a chronic disorder, results in gastrointestinal disturbances leading to poor patient compliance. Considering the favorable molecular weight, therapeutic dose, biological half-life and log P value of meloxicam for transdermal delivery, its fast dissolving microneedle patch, with an ability to breach the stratum corneum and efficiently deliver the cargo to deeper skin layers, were developed. Microneedle patch of low molecular weight polyvinyl alcohol and polyvinylpyrrolidone was prepared using Polydimethylsiloxane micromolds. The ratio of polyvinyl alcohol to polyvinyl pyrrolidone and solid content of matrix solution was optimized to achieve maximum needle strength. The optimized batch was extensively evaluated for in vitro dissolution, drug release, stability, ex vivo skin permeation/deposition, histopathology and in vivo pharmacodynamic study. The patch containing 9:1 polyvinyl alcohol to polyvinylpyrrolidone ratio with 50% solid content had shown maximum axial needle fracture force (0.9N) suitable for penetrating the skin. The optimized batch was found to be fast dissolving and released almost 100% drug in 60min following dissolution controlled kinetics. The formulation showed a significant drug deposition within skin (63.37%) and an improved transdermal flux (1.60μg/cm 2 /h) with a 2.58 fold enhancement in permeation as compared to plain drug solution. The formulation showed a comparable anti-inflammatory activity in rats when compared to its existing approved marketed oral tablet. Histopathology and stability evaluations demonstrated acceptable safety and shelf-life of the developed formulation. The successful verification of safety, efficacy and stability of microneedle patch advocated the suitability of the formulation for transdermal use. Copyright © 2017 Elsevier B.V. All rights reserved.

Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport.

Science.gov (United States)

Del Río-Sancho, S; Serna-Jiménez, C E; Sebastián-Morelló, M; Calatayud-Pascual, M A; Balaguer-Fernández, C; Femenía-Font, A; Kalia, Y N; Merino, V; López-Castellano, A

2017-01-30

Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist used in the treatment of moderate to severe dementia including the symptoms of Alzheimer's disease (AD). It is administered orally but compliance, swallowing problems and the routine use of multiple medications in elderly AD patients means that an alternative route of administration would be of interest. The aim of the present study was to develop memantine hydrochloride occlusive transdermal therapeutic systems (TTS) for passive and iontophoretic delivery across the skin. Polyvinyl pyrrolidone (PVP) and a mixture with polyvinyl alcohol (PVA) were employed as polymeric matrices. The study involved the TTS characterization in addition to quantification of the memantine transport across porcine skin in vitro. The evaluation of the TTS physical properties suggested that systems were made more mechanically resistant by including PVA (6%) or high concentrations of PVP (24%). Moreover, a linear correlation was observed between the concentration of PVP and the bioadhesion of the systems. Drug delivery experiments showed that the highest transdermal flux provided by a passive TTS (PVP 24% w/w limonene) was 8.89±0.81μgcm -2 h -1 whereas the highest iontophoretic transport was 46.4±3.6μgcm -2 h -1 . These innovative TTS would enable two dosage regimens that could lead to therapeutic plasma concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

Increased skin permeation efficiency of imperatorin via charged ultradeformable lipid vesicles for transdermal delivery.

Science.gov (United States)

Lin, Hongwei; Xie, Qingchun; Huang, Xin; Ban, Junfeng; Wang, Bo; Wei, Xing; Chen, Yanzhong; Lu, Zhufen

2018-01-01

The aim of this work was to develop a novel vesicular carrier, ultradeformable liposomes (UDLs), to expand the applications of the Chinese herbal medicine, imperatorin (IMP), and increase its transdermal delivery. In this study, we prepared IMP-loaded UDLs using the thin-film hydration method and evaluated their encapsulation efficiency, vesicle deformability, skin permeation, and the amounts accumulated in different depths of the skin in vitro. The influence of different charged surfactants on the properties of the UDLs was also investigated. The results showed that the UDLs containing cationic surfactants had high entrapment efficiency (60.32%±2.82%), an acceptable particle size (82.4±0.65 nm), high elasticity, and prolonged drug release. The penetration rate of IMP in cationic-UDLs was 3.45-fold greater than that of IMP suspension, which was the highest value among the vesicular carriers. UDLs modified with cationic surfactant also showed higher fluorescence intensity in deeper regions of the epidermis. The results of our study suggest that cationic surfactant-modified UDLs could increase the transdermal flux, prolong the release of the drug, and serve as an effective dermal delivery system for IMP.

Analyzing polymeric matrix for fabrication of a biodegradable microneedle array to enhance transdermal delivery.

Science.gov (United States)

Hwa, Kuo-Yuan; Chang, Vincent H S; Cheng, Yao-Yi; Wang, Yue-Da; Jan, Pey-Shynan; Subramani, Boopathi; Wu, Min-Ju; Wang, Bo-Kai

2017-09-19

Traditional drug delivery systems, using invasive, transdermal, and oral routes, are limited by various factors, such as the digestive system environment, skin protection, and sensory nerve stimulation. To improve the drug delivery system, we fabricated a polysaccharide-based, dissolvable microneedle-based array, which combines the advantages of both invasive and transdermal delivery systems, and promises to be an innovative solution for minimally invasive drug delivery. In this study, we designed a reusable aluminum mold that greatly improved the efficiency and convenience of microneedle fabrication. Physical characterization of the polysaccharides, individual or mixed at different ratios, was performed to identify a suitable molecule to fabricate the dissolvable microneedle. We used a vacuum deposition-based micro-molding method at low temperature to fabricate the model. Using a series of checkpoints from material into product, a systematic feedback mechanism was built into the "all-in-one" fabrication step, which helped to improve production yields. The physical properties of the fabricated microneedle were assessed. The cytotoxicity analysis and animal testing of the microneedle demonstrated the safety and compatibility of the microneedle, and the successful penetration and effective release of a model protein.

Liquid crystalline systems containing Vitamin E TPGS for the controlled transdermal nicotine delivery

Directory of Open Access Journals (Sweden)

Lívia Neves Borgheti-Cardoso

Full Text Available ABSTRACT Transdermal nicotine patches have been used in smoking cessation therapy, suggested for the treatment of skin disorders with eosinophilic infiltration and have been found to improve attention performance in patients with Alzheimer's disease and age-associated memory impairment. However, skin irritation with extended patch use is still a problem. The aim of this work was to develop a simple to prepare liquid crystalline system containing vitamin E TPGS that would be able to control nicotine delivery and reduce irritation and sensitization problems. The liquid crystalline phases were macroscopically characterized by visual analysis and examined microscopically under a polarized light microscope. Topical and transdermal delivery of nicotine were investigated in vitro using porcine ear skin mounted on a Franz diffusion cell. Nicotine skin permeation from the developed cubic phase followed zero-order kinetics (r = 0.993 and was significantly enhanced after 12 h when compared to the control formulation (nicotine solution (p < 0.05 (138.86 ± 20.44 and 64.91 ± 4.06 μg/cm2, respectively. Cubic phase was also able to target viable skin layers in comparison to control solution (8.18 ± 1.89 and 2.63 ± 2.51 μg/cm2, respectively. Further studies to evaluate skin sensitization and irritation are now necessary.

A New Drug Release Method in Early Development of Transdermal Drug Delivery Systems

Directory of Open Access Journals (Sweden)

Bing Cai

2012-01-01

Full Text Available In vitro drug release tests are a widely used tool to measure the variance between transdermal product performances and required by many authorities. However, the result cannot provide a good estimation of the in vivo drug release. In the present work, a new method for measuring drug release from patches has been explored and compared with the conventional USP apparatus 2 and 5 methods. Durogesic patches, here used as a model patch, were placed on synthetic skin simulator and three moisture levels (29, 57, 198 μL cm−2 were evaluated. The synthetic skin simulators were collected after 1, 2, 3, 4, 6, and 24 hours and extracted with pH 1.0 hydrochloric acid solution. The drug concentrations in the extractions were measured by isocratic reverse phase high-pressure liquid chromatography. The results showed that, with the increasing moisture level on the synthetic skin simulator, the drug release rate increased. In comparison with the conventional USP method, the drug release results performed by the new method were in more correlation to the release rate claimed in the product label. This new method could help to differentiate the drug release rates among assorted formulations of transdermal drug delivery systems in the early stage of development.

Effect of Asparagus racemosus extract on transdermal delivery of carvedilol: a mechanistic study.

Science.gov (United States)

Sapra, Bharti; Jain, Subheet; Tiwary, Ashok K

2009-01-01

This study was designed for investigating the effect of Asparagus racemosus (AR) extract and chitosan (CTN) in facilitating the permeation of carvedilol (CDL) across rat epidermis. Transdermal flux of carvedilol through heat-separated rat epidermis was investigated in vitro using vertical Keshary-Chien diffusion cells. Biophysical and microscopic manifestations of epidermis treated with AR extract, CTN, and AR extract-CTN mixture were investigated by using differential scanning calorimetry, transepidermal water loss, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Biochemical estimations of cholesterol, sphingosine, and triglycerides were carried out for treated excised as well as viable rat epidermis. The antihypertensive activity of the patches in comparison with that of oral carvedilol was studied in deoxycorticosterone acetate-induced hypertensive rats. The permeation of carvedilol across excised rat epidermis was significantly higher (p vehicle as compared to propylene glycol/ethanol (7:3) mixture. Epidermis obtained after 12 h treatment of viable rat skin with AR extract-CTN mixture showed significantly higher (p space, disordered lipid structure, and corneocyte detachment as observed in SEM and TEM suggested great potential of AR extract for use as percutaneous permeation enhancer. The developed transdermal patches of CDL containing AR extract-CTN mixture exhibited better performance as compared to oral administration in controlling hypertension in rats.

Electrospun polymeric nanofibers for transdermal drug delivery

Directory of Open Access Journals (Sweden)

Mahya Rahmani

2017-04-01

Full Text Available Conventional transdermal drug delivery systems (TDDS have been designed for drug delivery through the skin. These systems use the permeability property of stratum corneum, the outermost surface layer of the skin. Applying polymeric micro and nanofibers in drug delivery has recently attracted great attention and the electrospinning technique is the preferred method for polymeric micro-nanofibers fabrication with a great potential for drug delivery. More studies in the field of nanofibers containing drug are divided two categories: first, preparation and characterization of nanofibers containing drug and second, investigation of their therapeutic applications. Drugs used in electrospun nanofibers can be categorized into three main groups, including antibiotics and antimicrobial agents, anti-inflammatory agents and vitamins with therapeutic applications. In this paper, we review the application of electrospun polymeric scaffolds in TDDS and also introduce several pharmaceutical and therapeutic agents which have been used in polymer nanofibrous patches.

Mediated effect of ultrasound treated Diclofenac on mussel hemocytes: First evidence for the involvement of respiratory burst enzymes in the induction of DCF-mediated unspecific mode of action.

Science.gov (United States)

Toufexi, Eirini; Dailianis, Stefanos; Vlastos, Dimitris; Manariotis, Ioannis D

2016-06-01

The present study investigates the toxic behavior of diclofenac (DCF) before and after its ultrasound (US) treatment, as well as the involvement of intracellular target molecules, such as NADPH oxidase and NO synthase, in the DCF-induced adverse effects on hemocytes of mussel Mytilus galloprovincialis. In this context, appropriate volumes (350 and 500mL) of DCF solutions (at concentrations of 2, 2.5, 5 and 10mgL(-1)) were treated under different ultrasound operating conditions (frequency at 582 and 862kHz, electric power density at 133 and 167W) for assessing US method efficiency. In parallel, DCF and US DCF-mediated cytotoxic (in terms of cell viability measured with the use of neutral red uptake/NRU method), oxidative (in terms of superoxide anions/(.)O2(-), nitric oxides such as NO2(-) and lipid peroxidation products, such as malondialdehyde/MDA content) and genotoxic (DNA damage measured by the use of Comet assay method) effects were investigated in hemocytes exposed for 1h to 5, 10 and 100ngL(-1) and 1, 10 and 20μgL(-1) of DCF. The involvement of NADPH oxidase and NO synthase to the DCF-induced toxicity was further investigated by the use of 10μΜ L-NAME, a NO synthase inhibitor and 10μΜ DPI, a NADPH oxidase inhibitor. According to the results, 350mL of 2mgL(-1) DCF showed higher degradation (>50%) under 167W electric power density and frequency at 862kHz for 120min, compared to degradation in all other cases, followed by a significant elimination of its toxicity. Specifically, US DCF-treated hemocytes showed a significant attenuation of DCF-mediated cytotoxic, oxidative and genotoxic effects, which appeared to be caused by NADPH oxidase and NO synthase activation, since their inhibition was followed by a significant elimination of (.)O2(-) and NO2(-) generation and the concomitant oxidative damage within cells. The results of the present study showed for the first time that unspecific mode of action of DCF, associated with the induction of NADPH oxidase

Fractional Ablative Laser Followed by Transdermal Acoustic Pressure Wave Device to Enhance the Drug Delivery of Aminolevulinic Acid: In Vivo Fluorescence Microscopy Study.

Science.gov (United States)

Waibel, Jill S; Rudnick, Ashley; Nousari, Carlos; Bhanusali, Dhaval G

2016-01-01

Topical drug delivery is the foundation of all dermatological therapy. Laser-assisted drug delivery (LAD) using fractional ablative laser is an evolving modality that may allow for a greater precise depth of penetration by existing topical medications, as well as more efficient transcutaneous delivery of large drug molecules. Additional studies need to be performed using energy-driven methods that may enhance drug delivery in a synergistic manner. Processes such as iontophoresis, electroporation, sonophoresis, and the use of photomechanical waves aid in penetration. This study evaluated in vivo if there is increased efficacy of fractional CO2 ablative laser with immediate acoustic pressure wave device. Five patients were treated and biopsied at 4 treatment sites: 1) topically applied aminolevulinic acid (ALA) alone; 2) fractional ablative CO2 laser and topical ALA alone; 3) fractional ablative CO2 laser and transdermal acoustic pressure wave device delivery system; and 4) topical ALA with transdermal delivery system. The comparison of the difference in the magnitude of diffusion with both lateral spread of ALA and depth diffusion of ALA was measured by fluorescence microscopy. For fractional ablative CO2 laser, ALA, and transdermal acoustic pressure wave device, the protoporphyrin IX lateral fluorescence was 0.024 mm on average vs 0.0084 mm for fractional ablative CO2 laser and ALA alone. The diffusion for the acoustic pressure wave device was an order of magnitude greater. We found that our combined approach of fractional ablative CO2 laser paired with the transdermal acoustic pressure wave device increased the depth of penetration of ALA.

Ultrasound-enhanced delivery of targeted echogenic liposomes in a novel ex vivo mouse aorta model.

Science.gov (United States)

Hitchcock, Kathryn E; Caudell, Danielle N; Sutton, Jonathan T; Klegerman, Melvin E; Vela, Deborah; Pyne-Geithman, Gail J; Abruzzo, Todd; Cyr, Peppar E P; Geng, Yong-Jian; McPherson, David D; Holland, Christy K

2010-06-15

The goal of this study was to determine whether targeted, Rhodamine-labeled echogenic liposomes (Rh-ELIP) containing nanobubbles could be delivered to the arterial wall, and whether 1-MHz continuous wave ultrasound would enhance this delivery profile. Aortae excised from apolipoprotein-E-deficient (n=8) and wild-type (n=8) mice were mounted in a pulsatile flow system through which Rh-ELIP were delivered in a stream of bovine serum albumin. Half the aortae from each group were treated with 1-MHz continuous wave ultrasound at 0.49 MPa peak-to-peak pressure, and half underwent sham exposure. Ultrasound parameters were chosen to promote stable cavitation and avoid inertial cavitation. A broadband hydrophone was used to monitor cavitation activity. After treatment, aortic sections were prepared for histology and analyzed by an individual blinded to treatment conditions. Delivery of Rh-ELIP to the vascular endothelium was observed, and sub-endothelial penetration of Rh-ELIP was present in five of five ultrasound-treated aortae and was absent in those not exposed to ultrasound. However, the degree of penetration in the ultrasound-exposed aortae was variable. There was no evidence of ultrasound-mediated tissue damage in any specimen. Ultrasound-enhanced delivery within the arterial wall was demonstrated in this novel model, which allows quantitative evaluation of therapeutic delivery. Copyright (c) 2010 Elsevier B.V. All rights reserved.

TRANSDERMAL PERMEABILITY OF ESTRADIOL THROUGH THE HUMAN SKIN OF DIFFERENT BODY REGIONS IN VITRO

Institute of Scientific and Technical Information of China (English)

CHENGuo-Shen; GONGSai-Jun; DUJie; MARun-Zhen; ZHOURong-Rong; LIULiang-Chu

1989-01-01

Transdermal permeability of estradiol was carried out by using Valia-Chien double compartment permeation cells for the following regions of intact skin and skin without stratum corncum: chest, abdomen, hip, upper arm, thigh and back. The estradiol permeation rates and accumulative amounts within 72h in vitro were examined by HPLC. The results showed that the permeation rates of intact skin from different regions of the body

Microbubbles coupled to methotrexate-loaded liposomes for ultrasound-mediated delivery of methotrexate across the blood–brain barrier

Directory of Open Access Journals (Sweden)

Wang X

2014-10-01

Full Text Available Xiang Wang,1 Ping Liu,1 Weixiao Yang,1 Lu Li,1 Peijing Li,2 Zheng Liu,1 Zhongxiong Zhuo,1 Yunhua Gao1 1Department of Ultrasound, Xinqiao Hospital of the Third Military Medical University, Chongqing, 2Department of Ultrasound, General Hospital of the Jinan Military Area, Jinan, People’s Republic of China Abstract: Methotrexate (MTX is the single most effective agent for the treatment of primary central nervous system lymphoma. Currently, the delivery of MTX to the brain is achieved by high systemic doses, which cause severe long-term neurotoxicity, or intrathecal administration, which is highly invasive and may lead to infections or hemorrhagic complications. Acoustically active microbubbles have been developed as drug carriers for the noninvasive and brain-targeted delivery of therapeutics. However, their application is limited by their low drug-loading capacity. To overcome this limitation, we prepared microbubbles coupled to MTX-loaded liposomes using ZHIFUXIAN, a novel type of microbubbles with a superior safety profile and long circulation time. MTX-liposome-coupled microbubbles had a high drug-loading capacity of 8.91%±0.86%, and their size (2.64±0.93 µm in diameter was suitable for intravenous injection. When used with ultrasound, they showed more potent in vitro cytotoxicity against Walker-256 cancer cells than MTX alone or MTX-loaded liposomes. When Sprague-Dawley rats were exposed to sonication, administration of these MTX-liposome-coupled microbubbles via the tail vein led to targeted disruption of the blood–brain barrier without noticeable tissue or capillary damage. High-performance liquid chromatography analysis of the brain MTX concentration showed that MTX delivery to the brain followed the order of MTX-liposome-coupled microbubbles + ultrasound (25.3±2.4 µg/g > unmodified ZHIFUXIAN + MTX + ultrasound (18.6±2.2 µg/g > MTX alone (6.97±0.75 µg/g > MTX-liposome-coupled microbubbles (2.92±0.39 µg/g. Therefore

Preparation and evaluation of microemulsion-based transdermal delivery of total flavone of rhizoma arisaematis

Directory of Open Access Journals (Sweden)

Shen LN

2014-07-01

Full Text Available Li-Na Shen,1 Yong-Tai Zhang,1 Qin Wang,2 Ling Xu,2 Nian-Ping Feng11Department of Pharmaceutical Sciences, 2Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaAbstract: The aims of the present study were to investigate the skin permeation and cellular uptake of a microemulsion (ME containing total flavone of rhizoma arisaematis (TFRA, and to evaluate its effects on skin structure. Pseudo-ternary phase diagrams were constructed to evaluate ME regions with various surfactants and cosurfactants. Eight formulations of ­oil-in-water MEs were selected as vehicles, and in vitro skin-permeation experiments were performed to optimize the ME formulation and to evaluate its permeability, in comparison to that of an aqueous suspension. Laser scanning confocal microscopy and fluorescent-activated cell sorting were used to explore the cellular uptake of rhodamine 110-labeled ME in human epidermal keratinocytes (HaCaT and human embryonic skin fibroblasts (CCC-ESF-1. The structure of stratum corneum treated with ME was observed using a scanning electron microscope. Furthermore, skin irritation was tested to evaluate the safety of ME. ME formulated with 4% ethyl oleate (weight/weight, 18% Cremophor EL® (weight/weight, and 18% Transcutol® P, with 1% Azone to enhance permeation, showed good skin permeability. ME-associated transdermal fluxes of schaftoside and isoschaftoside, two major effective constituents of TFRA, were 3.72-fold and 5.92-fold higher, respectively, than those achieved using aqueous suspensions. In contrast, in vitro studies revealed that uptake by HaCaT and CCC-ESF-1 cells was lower with ME than with an aqueous suspension. Stratum corneum loosening and shedding was observed in nude mouse skin treated with ME, although ME produced no observable skin irritation in rabbits. These findings indicated that ME enhanced transdermal TFRA delivery effectively and showed

Management of chemotherapy-induced nausea and vomiting in patients receiving multiple-day highly or moderately emetogenic chemotherapy: role of transdermal granisetron.

Science.gov (United States)

Coluzzi, Flaminia; Mattia, Consalvo

2016-08-01

Granisetron transdermal delivery system (GTDS) is the first 5-HT3 drug to be transdermally delivered and represents a convenient alternative to oral and intravenous antiemetics for the treatment of chemotherapy-induced nausea and vomiting. GTDS is effective and well tolerated in patients receiving multiple-day moderate-to-highly emetogenic chemotherapy. In this setting noninferiority studies showed similar efficacy when GTDS was compared with intravenous and oral granisetron and intravenous palonosetron. GTDS has shown good cardiovascular safety; however, special caution is needed in patients at risk for developing excessive QTc interval prolongation and arrhythmias. So far, GTDS has been investigated for intravenous prevention in comparison with granisetron and palonosetron; however, further prospects open the route to future clinical investigations.

Ultrasound-mediated structural changes in cells revealed by FTIR spectroscopy: A contribution to the optimization of gene and drug delivery

Science.gov (United States)

Grimaldi, Paola; Di Giambattista, Lucia; Giordani, Serena; Udroiu, Ion; Pozzi, Deleana; Gaudenzi, Silvia; Bedini, Angelico; Giliberti, Claudia; Palomba, Raffaele; Congiu Castellano, Agostina

2011-12-01

Ultrasound effects on biological samples are gaining a growing interest concerning in particular, the intracellular delivery of drugs and genes in a safe and in a efficient way. Future progress in this field will require a better understanding of how ultrasound and acoustic cavitation affect the biological system properties. The morphological changes of cells due to ultrasound (US) exposure have been extensively studied, while little attention has been given to the cells structural changes. We have exposed two different cell lines to 1 MHz frequency ultrasound currently used in therapy, Jurkat T-lymphocytes and NIH-3T3 fibroblasts, both employed as models respectively in the apoptosis and in the gene therapy studies. The Fourier Transform Infrared (FTIR) Spectroscopy was used as probe to reveal the structural changes in particular molecular groups belonging to the main biological systems. The genotoxic damage of cells exposed to ultrasound was ascertained by the Cytokinesis-Block Micronucleus (CBMN) assay. The FTIR spectroscopy results, combined with multivariate statistical analysis, regarding all cellular components (lipids, proteins, nucleic acids) of the two cell lines, show that Jurkat cells are more sensitive to therapeutic ultrasound in the lipid and protein regions, whereas the NIH-3T3 cells are more sensitive in the nucleic acids region; a meaningful genotoxic effect is present in both cell lines only for long sonication times while in the Jurkat cells also a significant cytotoxic effect is revealed for long times of exposure to ultrasound.

A multi-frequency sparse hemispherical ultrasound phased array for microbubble-mediated transcranial therapy and simultaneous cavitation mapping.

Science.gov (United States)

Deng, Lulu; O'Reilly, Meaghan A; Jones, Ryan M; An, Ran; Hynynen, Kullervo

2016-12-21

Focused ultrasound (FUS) phased arrays show promise for non-invasive brain therapy. However, the majority of them are limited to a single transmit/receive frequency and therefore lack the versatility to expose and monitor the treatment volume. Multi-frequency arrays could offer variable transmit focal sizes under a fixed aperture, and detect different spectral content on receive for imaging purposes. Here, a three-frequency (306, 612, and 1224 kHz) sparse hemispherical ultrasound phased array (31.8 cm aperture; 128 transducer modules) was constructed and evaluated for microbubble-mediated transcranial therapy and simultaneous cavitation mapping. The array is able to perform effective electronic beam steering over a volume spanning (-40, 40) and (-30, 50) mm in the lateral and axial directions, respectively. The focal size at the geometric center is approximately 0.9 (2.1) mm, 1.7 (3.9) mm, and 3.1 (6.5) mm in lateral (axial) pressure full width at half maximum (FWHM) at 1224, 612, and 306 kHz, respectively. The array was also found capable of dual-frequency excitation and simultaneous multi-foci sonication, which enables the future exploration of more complex exposure strategies. Passive acoustic mapping of dilute microbubble clouds demonstrated that the point spread function of the receive array has a lateral (axial) intensity FWHM between 0.8-3.5 mm (1.7-11.7 mm) over a volume spanning (-25, 25) mm in both the lateral and axial directions, depending on the transmit/receive frequency combination and the imaging location. The device enabled both half and second harmonic imaging through the intact skull, which may be useful for improving the contrast-to-tissue ratio or imaging resolution, respectively. Preliminary in vivo experiments demonstrated the system's ability to induce blood-brain barrier opening and simultaneously spatially map microbubble cavitation activity in a rat model. This work presents a tool to investigate optimal strategies for non

Transdermal delivery of diclofenac using microemulsions.

Science.gov (United States)

Kweon, Jang-Hoon; Chi, Sang-Cheol; Park, Eun-Seok

2004-03-01

A transdermal preparation containing diclofenac diethylammonium (DDA) was developed using an O/W microemulsion system. Of the oils tested, lauryl alcohol was chosen as the oil phase of the microemulsion, as it showed a good solubilizing capacity and excellent skin permeation rate of the drug. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant and cosurfactant for microemulsion formation, and the effect of these additives on skin permeation of DDA was evaluated with excised rat skins. The optimum formulation of the microemulsion consisted of 1.16% of DDA, 5% of lauryl alcohol, 60% of water in combination with the 34.54% of Labrasol (surfactant)/ethanol (cosurfactant) (1:2). The efficiency of formulation in the percutaneous absorption of DDA was dependent upon the contents of water and lauryl alcohol as well as Labrasol:ethanol mixing ratio. It was concluded that the percutaneous absorption of DDA from microemulsions was enhanced with increasing the lauryl alcohol and water contents, and with decreasing the Labrasol:ethanol mixing ratio in the formulation.

Chemistry, manufacturing and controls in passive transdermal drug delivery systems.

Science.gov (United States)

Goswami, Tarun; Audett, Jay

2015-01-01

Transdermal drug delivery systems (TDDS) are used for the delivery of the drugs through the skin into the systemic circulation by applying them to the intact skin. The development of TDDS is a complex and multidisciplinary affair which involves identification of suitable drug, excipients and various other components. There have been numerous problems reported with respect to TDDS quality and performance. These problems can be reduced by appropriately addressing chemistry, manufacturing and controls requirements, which would thereby result in development of robust TDDS product and processes. This article provides recommendations on the chemistry, manufacturing and controls focusing on the unique technical aspects of TDDS.

Properties and in vitro drug release of hyaluronic acid-hydroxyethyl cellulose hydrogels for transdermal delivery of isoliquiritigenin.

Science.gov (United States)

Kong, Bong Ju; Kim, Ayoung; Park, Soo Nam

2016-08-20

In the present study, the properties of hydrogel systems based on hyaluronic acid (HA)-hydroxyethyl cellulose (HEC) were investigated for effective transdermal delivery of isoliquiritigenin (ILTG). Hydrogels were synthesized by chemical cross-linking, and network structures were characterised using scanning electron microscopy (SEM) and surface area analyser. Texture properties and swelling of HA-HEC hydrogels were found to be closely linked to cross-linker concentration and swelling medium. Water in HA-HEC hydrogels was found to exist mostly in the form of free water. The viscoelasticity and the network stabilization of the hydrogels were analysed via rheological studies. The release kinetics of the hydrogel followed Fickian diffusion mechanism. In an in vitro skin penetration study, the system substantially improved the delivery of ILTG into the skin. These results indicate that the hydrogel system composed of HA and HEC has potential as a transdermal delivery system, with cross-linking density and the swelling medium influencing the properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

A mechanics approach to the study of pressure sensitive adhesives and human skin for transdermal drug delivery applications

Science.gov (United States)

Taub, Marc Barry

Transdermal drug delivery is an alternative approach to the systemic delivery of pharmaceuticals where drugs are administered through the skin and absorbed percutaneously. This method of delivery offers several advantages over more traditional routes; most notably, the avoidance of the fast-pass metabolism of the liver and gut, the ability to offer controlled release rates, and the possibility for novel devices. Pressure sensitive adhesives (PSAs) are used to bond transdermal drug delivery devices to the skin because of their good initial and long-term adhesion, clean removability, and skin and drug compatibility. However, an understanding of the mechanics of adhesion to the dermal layer, together with quantitative and reproducible test methods for measuring adhesion, have been lacking. This study utilizes a mechanics-based approach to quantify the interfacial adhesion of PSAs bonded to selected substrates, including human dermal tissue. The delamination of PSA layers is associated with cavitation in the PSA followed by the formation of an extensive cohesive zone behind the debond tip. A quantitative metrology was developed to assess the adhesion and delamination of PSAs, such that it could be possible to easily distinguish between the adhesive characteristics of different PSA compositions and to provide a quantitative basis from which the reliability of adhesive layers bonded to substrates could be studied. A mechanics-based model was also developed to predict debonding in terms of the relevant energy dissipation mechanisms active during this process. As failure of transdermal devices may occur cohesively within the PSA layer, adhesively at the interface between the PSA and the skin, or cohesively between the corneocytes that comprise the outermost layer of the skin, it was also necessary to explore the mechanical and fracture properties of human skin. The out-of-plane delamination of corneocytes was studied by determining the strain energy release rate during

Enhanced Topical and Transdermal Delivery of Antineoplastic and Antiviral Acyclic Nucleoside Phosphonate cPr-PMEDAP

Czech Academy of Sciences Publication Activity Database

Vávrová, K.; Kovaříková, P.; Školová, B.; Líbalová, M.; Roh, J.; Čáp, R.; Holý, Antonín; Hrabálek, A.

2011-01-01

Roč. 28, č. 12 (2011), s. 3105-3115 ISSN 0724-8741 R&D Projects: GA MŠk 1M0508 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * antivirals * antineoplastics * permeation enhancer * topical skin application * transdermal delivery Subject RIV: CC - Organic Chemistry Impact factor: 4.093, year: 2011

Effects of Sizes and Conformations of Fish-Scale Collagen Peptides on Facial Skin Qualities and Transdermal Penetration Efficiency

Directory of Open Access Journals (Sweden)

Huey-Jine Chai

2010-01-01

Full Text Available Fish-scale collagen peptides (FSCPs were prepared using a given combination of proteases to hydrolyze tilapia (Oreochromis sp. scales. FSCPs were determined to stimulate fibroblast cells proliferation and procollagen synthesis in a time- and dose-dependent manner. The transdermal penetration capabilities of the fractionationed FSCPs were evaluated using the Franz-type diffusion cell model. The heavier FSCPs, 3500 and 4500 Da, showed higher cumulative penetration capability as opposed to the lighter FSCPs, 2000 and 1300 Da. In addition, the heavier seemed to preserve favorable coiled structures comparing to the lighter that presents mainly as linear under confocal scanning laser microscopy. FSCPs, particularly the heavier, were concluded to efficiently penetrate stratum corneum to epidermis and dermis, activate fibroblasts, and accelerate collagen synthesis. The heavier outweighs the lighter in transdermal penetration likely as a result of preserving the given desired structure feature.

Perioperative analgesia with a buprenorphine transdermal patch for hallux valgus surgery: a prospective, randomized, controlled study

Directory of Open Access Journals (Sweden)

Xu C

2018-04-01

Full Text Available Can Xu, Mingqing Li, Chenggong Wang, Hui Li, Hua Liu Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China Purpose: Hallux valgus surgery often results in significant postoperative pain. Adequate control of pain is essential for patient satisfaction and improves the outcome of the procedure. This study aimed to investigate the perioperative analgesic effect of a buprenorphine transdermal patch in patients who underwent hallux valgus surgery.Patients and methods: A total of 90 patients were randomly divided into the following three groups based on the perioperative analgesic method: flurbiprofen axetil intravenous injection (Group F, oral celecoxib (Group C, and buprenorphine transdermal delivery system (BTDS (Group BTDS. The pain status, degree of satisfaction, adverse effects, and administration of tramadol hydrochloride for uncontrolled pain were recorded on the night before surgery, postoperative day 1, postoperative day 2, and postoperative day 3.Results: The BTDS could effectively control perioperative pain for patients undergoing ­hallux valgus surgery. The analgesic effect of the BTDS was better than that of oral celecoxib. In addition, statistically significant differences were not observed in the visual analog scale (VAS scores, adverse effects, and rescue analgesia between the patients who received the BTDS and the patients who received the flurbiprofen axetil intravenous injection. However, the degree of patient satisfaction of the BTDS group was significantly higher (P<0.05 than that of the other two groups.Conclusion: The BTDS (a preemptive analgesia regimen could exert an analgesic effect during the perioperative period for patients who had received hallux valgus surgery, and this effect is beneficial for sustaining postoperative physiological and psychological states and promoting functional rehabilitation. Keywords: hallux valgus, buprenorphine transdermal

Microneedle Coating Techniques for Transdermal Drug Delivery

Directory of Open Access Journals (Sweden)

Rita Haj-Ahmad

2015-11-01

Full Text Available Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates.

Gene delivery systems by the combination of lipid bubbles and ultrasound.

Science.gov (United States)

Negishi, Yoichi; Endo-Takahashi, Yoko; Maruyama, Kazuo

2016-11-28

Gene therapy is promising for the treatment of many diseases including cancers and genetic diseases. From the viewpoint of safety, ultrasound (US)-mediated gene delivery with nano/ microbubbles was recently developed as a novel non-viral vector system. US-mediated gene delivery using nano/microbubbles are able to produce transient changes in the permeability of the cell membrane after US-induced cavitation while reducing cellular damage and enables the tissue-specific or the site-specific intracellular delivery of gene both in vitro and in vivo. We have recently developed novel lipid nanobubbles (Lipid Bubbles). These nanobubbles can also be used to enhance the efficacy of the US-mediated genes (plasmid DNA, siRNA, and miRNA etc.) delivery. In this review, we describe US-mediated delivery systems combined with nano/microbubbles and discuss their feasibility as non-viral vector systems.

Use and cardiovascular safety of transdermal and other granisetron preparations in cancer management

OpenAIRE

Mason, Jay W; Moon, Thomas E

2013-01-01

Jay W Mason,1 Thomas E Moon2 1School of Medicine, University of Utah, Salt Lake City, UT, 2Tarizona eHealth Services, Inc, Emeryville, CA, USA Abstract: 5-HT3 antagonists have been available as oral and intravenous preparations for decades. The availability more recently of transdermal granisetron and the anticipated availability of a subcutaneous granisetron preparation have provided helpful alternatives to patients, and these preparations have been shown to have less potential to prolong Q...

Low-Intensity Pulsed Ultrasound Enhances Nerve Growth Factor-Induced Neurite Outgrowth through Mechanotransduction-Mediated ERK1/2-CREB-Trx-1 Signaling.

Science.gov (United States)

Zhao, Lu; Feng, Yi; Hu, Hong; Shi, Aiwei; Zhang, Lei; Wan, Mingxi

2016-12-01

Enhancing the action of nerve growth factor (NGF) is a potential therapeutic approach to neural regeneration. To facilitate neural regeneration, we investigated whether combining low-intensity pulsed ultrasound (LIPUS) and NGF could promote neurite outgrowth, an essential process in neural regeneration. In the present study, PC12 cells were subjected to a combination of LIPUS (1 MHz, 30 or 50 mW/cm 2 , 20% duty cycle and 100-Hz pulse repetition frequency, 10 min every other day) and NGF (50 ng/mL) treatment, and then neurite outgrowth was compared. Our findings indicated that the combined treatment with LIPUS (50 mW/cm 2 ) and NGF (50 ng/mL) promotes neurite outgrowth that is comparable to that achieved by NGF (100 ng/mL) treatment alone. LIPUS significantly increased NGF-induced neurite length, but not neurite branching. These effects were attributed to the enhancing effects of LIPUS on NGF-induced phosphorylation of ERK1/2 and CREB and the expression of thioredoxin (Trx-1). Furthermore, blockage of stretch-activated ion channels with Gd 3+ suppressed the stimulating effects of LIPUS on NGF-induced neurite outgrowth and the downstream signaling activation. Taken together, our findings suggest that LIPUS enhances NGF-induced neurite outgrowth through mechanotransduction-mediated signaling of the ERK1/2-CREB-Trx-1 pathway. The combination of LIPUS and NGF could potentially be used for the treatment of nerve injury and neurodegenerative diseases. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Improving arteriovenous fistula patency: Transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation

Science.gov (United States)

MacAskill, Mark G.; Watson, David G.; Ewart, Marie-Ann; Wadsworth, Roger; Jackson, Andrew; Aitken, Emma; MacKenzie, Graeme; Kingsmore, David; Currie, Susan; Coats, Paul

2015-01-01

Creation of an autologous arteriovenous fistula (AVF) for vascular access in haemodialysis is the modality of choice. However neointimal hyperplasia and loss of the luminal compartment result in AVF patency rates of ~ 60% at 12 months. The exact cause of neointimal hyperplasia in the AVF is poorly understood. Vascular trauma has long been associated with hyperplasia. With this in mind in our rabbit model of AVF we simulated cannulation autologous to that undertaken in vascular access procedures and observed significant neointimal hyperplasia as a direct consequence of cannulation. The neointimal hyperplasia was completely inhibited by topical transdermal delivery of the non-steroidal anti-inflammatory (NSAID) diclofenac. In addition to the well documented anti-inflammatory properties we have identified novel anti-proliferative mechanisms demonstrating diclofenac increases AMPK-dependent signalling and reduced expression of the cell cycle protein cyclin D1. In summary prophylactic transdermal delivery of diclofenac to the sight of AVF cannulation prevents adverse neointimal hyperplasic remodelling and potentially offers a novel treatment option that may help prolong AVF patency and flow rates. PMID:25866325

Transdermal agomelatine microemulsion gel: pyramidal screening, statistical optimization and in vivo bioavailability.

Science.gov (United States)

Said, Mayada; Elsayed, Ibrahim; Aboelwafa, Ahmed A; Elshafeey, Ahmed H

2017-11-01

Agomelatine is a new antidepressant having very low oral drug bioavailability less than 5% due to being liable to extensive hepatic 1st pass effect. This study aimed to deliver agomelatine by transdermal route through formulation and optimization of microemulsion gel. Pyramidal screening was performed to select the most suitable ingredients combinations and then, the design expert software was utilized to optimize the microemulsion formulations. The independent variables of the employed mixture design were the percentages of capryol 90 as an oily phase (X 1 ), Cremophor RH40 and Transcutol HP in a ratio of (1:2) as surfactant/cosurfactant mixture 'S mix ' (X 2 ) and water (X 3 ). The dependent variables were globule size, optical clarity, cumulative amount permeated after 1 and 24 h, respectively (Q1 and Q 24 ) and enhancement ratio (ER). The optimized formula was composed of 5% oil, 45% S mix and 50% water. The optimized microemulsion formula was converted into carbopol-based gel to improve its retention on the skin. It enhanced the drug permeation through rat skin with an enhancement ratio of 37.30 when compared to the drug hydrogel. The optimum ME gel formula was found to have significantly higher C max , AUC 0-24 h and AUC 0-∞ than that of the reference agomelatine hydrogel and oral solution. This could reveal the prosperity of the optimized microemulsion gel formula to augment the transdermal bioavailability of agomelatine.

General Ultrasound Imaging

Medline Plus

Full Text Available ... ultrasound. top of page How does the procedure work? Ultrasound imaging is based on the same principles ... modality for the diagnosis and monitoring of pregnant women and their unborn babies. Ultrasound provides real-time ...

General Ultrasound Imaging

Medline Plus

Full Text Available ... of page How is the procedure performed? For most ultrasound exams, you will be positioned lying face- ... Ultrasound examinations are painless and easily tolerated by most patients. Ultrasound exams in which the transducer is ...

General Ultrasound Imaging

Medline Plus

Full Text Available ... medical test that helps physicians diagnose and treat medical conditions. Conventional ultrasound displays the images in thin, flat sections of the body. Advancements in ultrasound technology include three-dimensional (3-D) ultrasound that formats ...

General Ultrasound Imaging

Medline Plus

Full Text Available ... D images. A Doppler ultrasound study may be part of an ultrasound examination. Doppler ultrasound , also called ... terms of the distance traveled per unit of time, rather than as a color picture. It can ...

Correction for photobleaching in dynamic fluorescence microscopy: application in the assessment of pharmacokinetic parameters in ultrasound-mediated drug delivery

International Nuclear Information System (INIS)

Derieppe, M; Bos, C; De Greef, M; Moonen, C; Denis de Senneville, B

2016-01-01

We have previously demonstrated the feasibility of monitoring ultrasound-mediated uptake of a hydrophilic model drug in real time with dynamic confocal fluorescence microscopy. In this study, we evaluate and correct the impact of photobleaching to improve the accuracy of pharmacokinetic parameter estimates. To model photobleaching of the fluorescent model drug SYTOX Green, a photobleaching process was added to the current two-compartment model describing cell uptake. After collection of the uptake profile, a second acquisition was performed when SYTOX Green was equilibrated, to evaluate the photobleaching rate experimentally. Photobleaching rates up to 5.0 10 −3 s −1 were measured when applying power densities up to 0.2 W.cm −2 . By applying the three-compartment model, the model drug uptake rate of 6.0 10 −3 s −1 was measured independent of the applied laser power. The impact of photobleaching on uptake rate estimates measured by dynamic fluorescence microscopy was evaluated. Subsequent compensation improved the accuracy of pharmacokinetic parameter estimates in the cell population subjected to sonopermeabilization. (paper)

The effects of titanium dioxide coatings on light-derived heating and transdermal heat transfer in bovine skin

NARCIS (Netherlands)

Bartle, S J; Thomson, D U; Gehring, R; van der Merwe, B. D.

2017-01-01

The effects of titanium dioxide coatings of bovine hides on light absorption and transdermal transfer of light-derived heat were investigated. Four hair-on rug hides from Holstein cattle were purchased. Twelve samples about 20 cm on a side were cut from each hide; nine from the black-colored areas,

Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals.

Science.gov (United States)

Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

2017-01-01

Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations.

Ultrasound in Space Medicine

Science.gov (United States)

Dulchavsky, Scott A.; Sargsyan, A.E.

2009-01-01

This slide presentation reviews the use of ultrasound as a diagnostic tool in microgravity environments. The goals of research in ultrasound usage in space environments are: (1) Determine accuracy of ultrasound in novel clinical conditions. (2) Determine optimal training methodologies, (3) Determine microgravity associated changes and (4) Develop intuitive ultrasound catalog to enhance autonomous medical care. Also uses of Ultrasound technology in terrestrial applications are reviewed.

Enhanced transdermal bioavailability of testosterone propionate via surfactant-modified ethosomes

Directory of Open Access Journals (Sweden)

Meng S

2013-08-01

Full Text Available Shu Meng,1 Zaixing Chen,2 Liqun Yang,1 Wei Zhang,1 Danhua Liu,1 Jing Guo,1 Yanmin Guan,1 Jianxin Li11Liaoning Research Institute of Family Planning, Shenyang, Liaoning Province, People's Republic of China; 2School of Pharmacy, China Medical University, Shenyang, Liaoning Province, People's Republic of ChinaAbstract: The current investigation aimed to evaluate the transdermal potential of novel testosterone propionate (TP ethosomes and liposomes prepared by surfactant modification. The effect of hexadecyl trimethyl ammonium bromide and cremophor EL-35 on the particle size and zeta potential of the prepared vesicles was investigated. The entrapment efficiency and stability, as well as in vitro and in vivo skin permeation, were studied with the various techniques, such as differential scanning calorimetry, confocal laser scanning microscopy, transmission electron microscopy, dynamic light scattering, and so on. The results indicated that the ethosomes were defined as spherical, unilamellar structures with low polydispersity (0.100 ± 0.015 and nanometric size (156.5 ± 3.5 nm. The entrapment efficiency of TP in ethosomal and liposomal carriers was 92.7% ± 3.7% and 64.7% ± 2.1%, respectively. The stability profile of the prepared TP ethosomal system assessed for 120 days revealed very low aggregation and very low growth in vesicular size. TP ethosomes also provided an enhanced transdermal flux of 37.85 ± 2.8 µg/cm2/hour and a decreased lag time of 0.18 hours across mouse skin. The skin permeation efficiency of the TP ethosomes as further assessed by confocal laser scanning microscopy revealed enhanced permeation of rhodamine red-loaded formulations to the deeper layers of the skin (260 µm than that of the liposomal formation (120 µm.Keywords: testosterone propionate, surfactant-modified ethosomes, liposomes, confocal laser scanning microscopy

Nanoemulsions as vehicles for transdermal delivery of glycyrrhizin

Directory of Open Access Journals (Sweden)

Ranjit Kumar Harwansh

2011-12-01

Full Text Available The present investigation aims to evaluate an isotropic and thermodynamically stable nanoemulsion formulation for transdermal delivery of glycyrrhizin (GZ, with minimum surfactant and cosurfactant (Smix concentrations that could improve its solubility, permeation enhancement, and stability. Pseudo-ternary phase diagrams were developed and various nanoemulsion formulations were prepared using soyabean oil as oil, Span 80, Brij 35 as a surfactant and isopropyl alcohol as a cosurfactant. Nanoemulsion formulations that passed the thermodynamic stability tests were characterized for pH, viscosity and droplet size using a transmission electron microscopy. The transdermal ability of glycyrrhizin through human cadaver skin was determined using Franz diffusion cells. The in vitro skin permeation profile of the optimized nanoemulsion formulation (NE2 was compared to that of conventional gel. A significant increase in permeability parameters such as steady-state flux (Jss and permeability coefficient (Kp was observed in the optimized nanoemulsion formulation (NE2, which consisted of 1% wt/wt of mono ammonium glycyrrhizinate (MAG, 32.4% Span 80, 3.7% Brij 35, 10% isopropyl alcohol, 46.5% soyabean oil and 6.4% distilled water. No obvious skin irritation was observed for the studied nanoemulsion formulation (NE2 or the gel. The results indicated that nanoemulsions are promising vehicles for transdermal delivery of glycyrrhizin through human cadaver skin, without the use of additional permeation enhancers, because excipients of nanoemulsions act as permeation enhancers themselves.O objetivo da investigação é avaliar uma nanoemulsão isotrópica termodinamicamente estável para a administração transdérmica da glicirrizina (GZ, com concentrações mínimas de tensoativo e co-tensoativo (Smix, que poderiam melhorar a sua solubilidade, a permeação e a estabilidade. Os diagramas pseudo-ternários de fase foram desenvolvidos e diversas nanoemulsões foram

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... through blood vessels. Ultrasound imaging is a noninvasive medical test that helps physicians diagnose and treat medical conditions. There are three types of pelvic ultrasound: ...

Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

Energy Technology Data Exchange (ETDEWEB)

Bhunia, Tridib [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India); Goswami, Luna [KIIT School of Biotechnology, KIIT University Campus XI, Patia, Bhubaneswar 751024, Orissa (India); Chattopadhyay, Dipankar [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India); Bandyopadhyay, Abhijit, E-mail: abpoly@caluniv.ac.in [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India)

2011-08-15

Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

Science.gov (United States)

Bhunia, Tridib; Goswami, Luna; Chattopadhyay, Dipankar; Bandyopadhyay, Abhijit

2011-08-01

Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

International Nuclear Information System (INIS)

Bhunia, Tridib; Goswami, Luna; Chattopadhyay, Dipankar; Bandyopadhyay, Abhijit

2011-01-01

Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

General Ultrasound Imaging

Medline Plus

Full Text Available ... transducer sends out high-frequency sound waves (that the human ear cannot hear) into the body and then ... ultrasound , there are no known harmful effects on humans. top of page What are the limitations of General Ultrasound Imaging? Ultrasound waves are ...

Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis.

Science.gov (United States)

Katsumi, Hidemasa; Tanaka, Yutaro; Hitomi, Kaori; Liu, Shu; Quan, Ying-Shu; Kamiyama, Fumio; Sakane, Toshiyasu; Yamamoto, Akira

2017-08-17

To improve the transdermal bioavailability and safety of alendronate (ALN), a nitrogen-containing bisphosphonate, we developed self-dissolving microneedle arrays (MNs), in which ALN is loaded only at the tip portion of micron-scale needles by a dip-coating method (ALN(TIP)-MN). We observed micron-scale pores in rat skin just after application of ALN(TIP)-MN, indicating that transdermal pathways for ALN were created by MN. ALN was rapidly released from the tip of MNs as observed in an in vitro release study. The tip portions of MNs completely dissolved in the rat skin within 5 min after application in vivo. After application of ALN(TIP)-MN in mice, the plasma concentration of ALN rapidly increased, and the bioavailability of ALN was approximately 96%. In addition, the decrease in growth plate was effectively suppressed by this efficient delivery of ALN in a rat model of osteoporosis. Furthermore, no skin irritation was observed after application of ALN(TIP)-MN and subcutaneous injection of ALN, while mild skin irritation was induced by whole-ALN-loaded MN (ALN-MN)-in which ALN is contained in the whole of the micron-scale needles fabricated from hyaluronic acid-and intradermal injection of ALN. These findings indicate that ALN(TIP)-MN is a promising transdermal formulation for the treatment of osteoporosis without skin irritation.

Clinical diagnostic ultrasound

International Nuclear Information System (INIS)

Barnett, E.; Morley, P.

1986-01-01

This textbook on diagnostic ultrasound covers the main systems, with emphasis being placed on the clinical application of diagnostic ultrasound in everyday practice. It provides not only a textbook for postgraduates (particularly FRCR candidates), but also a reference work for practitioners of clinical ultrasound and clinicians generally

Quantitative characterization of chitosan in the skin by Fourier-transform infrared spectroscopic imaging and ninhydrin assay: application in transdermal sciences.

Science.gov (United States)

Nawaz, A; Wong, T W

2016-07-01

The chitosan has been used as the primary excipient in transdermal particulate dosage form design. Its distribution pattern across the epidermis and dermis is not easily accessible through chemical assay and limited to radiolabelled molecules via quantitative autoradiography. This study explored Fourier-transform infrared spectroscopy imaging technique with built-in microscope as the means to examine chitosan molecular distribution over epidermis and dermis with the aid of histology operation. Fourier-transform infrared spectroscopy skin imaging was conducted using chitosan of varying molecular weights, deacetylation degrees, particle sizes and zeta potentials, obtained via microwave ligation of polymer chains at solution state. Both skin permeation and retention characteristics of chitosan increased with the use of smaller chitosan molecules with reduced acetyl content and size, and increased positive charge density. The ratio of epidermal to dermal chitosan content decreased with the use of these chitosan molecules as their accumulation in dermis (3.90% to 18.22%) was raised to a greater extent than epidermis (0.62% to 1.92%). A larger dermal chitosan accumulation nonetheless did not promote the transdermal polymer passage more than the epidermal chitosan. A small increase in epidermal chitosan content apparently could fluidize the stratum corneum and was more essential to dictate molecular permeation into dermis and systemic circulation. The histology technique aided Fourier-transform infrared spectroscopy imaging approach introduces a new dimension to the mechanistic aspect of chitosan in transdermal delivery. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

Standards of the Polish Ultrasound Society – update. Ultrasound examination of thyroid gland and ultrasound-guided thyroid biopsy

Directory of Open Access Journals (Sweden)

Anna Trzebińska

2014-03-01

Full Text Available Ultrasonography is a primary imaging technique in patients with suspected thyroid disease. It allows to assess the location, size and echostructures of the thyroid gland as well as detect focal lesions, along with indication of their size, echogenicity, echostructure and vascularity. Based on these features, ultrasound examination allows to predict abnormal focal lesions for biopsy and monitor the biopsy needle track. This paper presents the standards of thyroid ultrasound examination regarding ultrasound apparatus technical requirements, scanning techniques, readings, measurements, and the description of the examination. It discusses the ultrasound features of increased malignancy risk in focal lesions (nodules found in the thyroid gland. It presents indications for fine needle aspiration biopsy of the thyroid gland for the visibility of single nodules (focal lesions and numerous lesions as well as discusses contraindications for thyroid biopsy. It describes the biopsy technique, possible complications and rules for post-biopsy monitoring of benign lesions. The paper is an update of the Standards of the Polish Ultrasound Society issued in 2011. It has been prepared on the basis of current literature, taking into account the information contained in the following publications: Thyroid ultrasound examination and Recommendations of the Polish Ultrasound Society for the performance of the FNAB of the thyroid.

[Effects of Frankincense and Myrrh essential oil on transdermal absorption in vitro of Chuanxiong and penetration mechanism of skin blood flow].

Science.gov (United States)

Zhu, Xiao-Fang; Luo, Jing; Guan, Yong-Mei; Yu, Ya-Ting; Jin, Chen; Zhu, Wei-Feng; Liu, Hong-Ning

2017-02-01

The aim of this paper was to explore the effects of Frankincense and Myrrh essential oil on transdermal absorption in vitro of Chuanxiong, and to investigate the possible penetration mechanism of their essential oil from the perspective of skin blood perfusion changes. Transdermal tests were performed in vitro with excised mice skin by improved Franz diffusion cells. The cumulative penetration amounts of ferulic acid in Chuanxiong were determined by HPLC to investigate the effects of Frankincense and Myrrh essential oil on transdermal permeation properties of Chuanxiong. Simultaneously, the skin blood flows were determined by laser flow doppler. The results showed that the cumulative penetration amount of ferulic acid in Chuanxiong was (8.13±0.76) μg•cm⁻² in 24 h, and was (48.91±4.87), (57.80±2.86), (63.34±4.56), (54.17±4.40), (62.52±7.79) μg•cm⁻² respectively in Azone group, Frankincense essential oil group, Myrrh essential oil, frankincense and myrrh singly extracted essential oil mixture group, and frankincense and myrrh mixed extraction essential oil group. The enhancement ratios of each essential oil groups were 7.68, 8.26, 7.26, 8.28, which were slightly greater than 6.55 in Azone group. In addition, as compared with the conditions before treatment, there were significant differences and obvious increasing trend in blood flow of rats in Frankincense essential oil group, Myrrh essential oil group, frankincense and myrrh singly extracted essential oil mixture group, and frankincense and myrrh mixed extraction essential oil group when were dosed at 10, 20, 30, 10 min respectively, indicating that the skin blood flows were increased under the effects of Frankincense and Myrrh essential oil to a certain extent. Thus, Frankincense and Myrrh essential oil had certain effect on promoting permeability of Chuanxiong both before and after drug combination, and may promote the elimination of drugs from epidermis to dermal capillaries through increase of

Microemulsions based transdermal drug delivery systems.

Science.gov (United States)

Vadlamudi, Harini C; Narendran, Hyndavi; Nagaswaram, Tejeswari; Yaga, Gowri; Thanniru, Jyotsna; Yalavarthi, Prasanna R

2014-01-01

Since the discovery of microemulsions by Jack H Schulman, there has been huge progress made in applying microemulsion systems in plethora of research and industrial process. Microemulsions are optically isotropic systems consisting of water, oil and amphiphile. These systems are beneficial due to their thermodynamic stability, optical clarity, ease of preparation, higher diffusion and absorption rates. Moreover, it has been reported that the ingredients of microemulsion can effectively overcome the diffusion barrier and penetrate through the stratum corneum of the skin. Hence it becomes promising for both transdermal and dermal drug delivery. However, low viscosity of microemulsion restrains its applicability in pharmaceutical industry. To overcome the above drawback, the low viscous microemulsions were added to viscous gel bases to potentiate its applications as topical drug delivery systems so that various drug related toxic effects and erratic drug absorption can be avoided. The present review deals with the microemulsions, various techniques involved in the development of organic nanoparticles. The review emphasized on microemulsion based systems such as hydrogels and organogels. The physicochemical characteristics, mechanical properties, rheological and stability principles involved in microemulsion based viscous gels were also explored.

Transdermal testosterone replacement therapy in men

Science.gov (United States)

Ullah, M Iftekhar; Riche, Daniel M; Koch, Christian A

2014-01-01

Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule. PMID:24470750

Current and future technological advances in transdermal gene delivery.

Science.gov (United States)

Chen, Xianfeng

2017-12-19

Transdermal gene delivery holds significant advantages as it is able to minimize the problems of systemic administration such as enzymatic degradation, systemic toxicity, and poor delivery to target tissues. This technology has the potential to transform the treatment and prevention of a range of diseases. However, the skin poses a great barrier for gene delivery because of the "bricks-and-mortar" structure of the stratum corneum and the tight junctions between keratinocytes in the epidermis. This review systematically summarizes the typical physical and chemical approaches to overcome these barriers and facilitate gene delivery via skin for applications in vaccination, wound healing, skin cancers and skin diseases. Next, the advantages and disadvantages of different approaches are discussed and the insights for future development are provided. Copyright © 2017 Elsevier B.V. All rights reserved.

Low-Intensity Ultrasound-Induced Anti-inflammatory Effects Are Mediated by Several New Mechanisms Including Gene Induction, Immunosuppressor Cell Promotion, and Enhancement of Exosome Biogenesis and Docking

Directory of Open Access Journals (Sweden)

Qian Yang

2017-10-01

Full Text Available Background: Low-intensity ultrasound (LIUS was shown to be beneficial in mitigating inflammation and facilitating tissue repair in various pathologies. Determination of the molecular mechanisms underlying the anti-inflammatory effects of LIUS allows to optimize this technique as a therapy for the treatment of malignancies and aseptic inflammatory disorders.Methods: We conducted cutting-edge database mining approaches to determine the anti-inflammatory mechanisms exerted by LIUS.Results: Our data revealed following interesting findings: (1 LIUS anti-inflammatory effects are mediated by upregulating anti-inflammatory gene expression; (2 LIUS induces the upregulation of the markers and master regulators of immunosuppressor cells including MDSCs (myeloid-derived suppressor cells, MSCs (mesenchymal stem cells, B1-B cells and Treg (regulatory T cells; (3 LIUS not only can be used as a therapeutic approach to deliver drugs packed in various structures such as nanobeads, nanospheres, polymer microspheres, and lipidosomes, but also can make use of natural membrane vesicles as small as exosomes derived from immunosuppressor cells as a novel mechanism to fulfill its anti-inflammatory effects; (4 LIUS upregulates the expression of extracellular vesicle/exosome biogenesis mediators and docking mediators; (5 Exosome-carried anti-inflammatory cytokines and anti-inflammatory microRNAs inhibit inflammation of target cells via multiple shared and specific pathways, suggesting exosome-mediated anti-inflammatory effect of LIUS feasible; and (6 LIUS-mediated physical effects on tissues may activate specific cellular sensors that activate downstream transcription factors and signaling pathways.Conclusions: Our results have provided novel insights into the mechanisms underlying anti-inflammatory effects of LIUS, and have provided guidance for the development of future novel therapeutic LIUS for cancers, inflammatory disorders, tissue regeneration and tissue repair.

Acceptability of a transdermal gel-based male hormonal contraceptive in a randomized controlled trial☆, ☆☆, ★

Science.gov (United States)

Roth, Mara Y.; Shih, Grace; Ilani, Niloufar; Wang, Christina; Page, Stephanie T.; Bremner, William J.; Swerdloff, Ronald S.; Sitruk-Ware, Regine; Blithe, Diana L.; Amory, John K.

2014-01-01

Objective Fifty percent of pregnancies in the United States are unintended despite numerous contraceptive methods available to women. The only male contraceptive methods, vasectomy and condoms, are used by 10% and 16% of couples, respectively. Prior studies have shown efficacy of male hormonal contraceptives in development, but few have evaluated patient acceptability and potential use if commercially available. The objective of this study is to determine if a transdermal gel-based male hormonal contraceptive regimen, containing testosterone and Nestorone® gels, would be acceptable to study participants as a primary contraceptive method. Study Design As part of a three-arm, 6-month, double-blind, randomized controlled trial of testosterone and nestorone gels at two academic medical centers, subjects completed a questionnaire to assess the acceptability of the regimen. Of the 99 men randomized, 79 provided data for analysis. Results Overall, 56% (44/79) of men were satisfied or extremely satisfied with this gel-based method of contraception, and 51% (40/79) reported that they would recommend this method to others. One third of subjects (26/79) reported that they would use this as their primary method of contraception if it were commercially available today. However, men with concerns about sexually transmitted disease were significantly less satisfied than men without such concerns (p=0.03). Conclusions A majority of the men who volunteered to participate in this trial of an experimental male hormonal contraceptive were satisfied with this transdermal male hormonal contraceptive. If commercially available, a combination of topical nesterone and testosterone gels could provide a reversible, effective method of contraception that is appealing to men. Implications A substantial portion of men report they would use this transdermal male contraceptive regimen if commercially available. This method would provide a novel, reversible method of contraception for men, whose

Comparison of an Additional Transdermal Fentanyl Patch Compared to Intravenous NSAID and Opioid Analgesics within 24 Hours of an Uterine Artery Embolization for Myoma and Adenomyosis

International Nuclear Information System (INIS)

Song, Suk Yun; Kang, Byung Chul; Rho, Kyung Min

2011-01-01

To evaluate the effectiveness of an additional transdermal fentanyl patch compared to intravenous analgesics in pain control during the 24-hour period following uterine artery embolization (UAE) for myoma and adenomyosis. Between September 2009 and August 2010, 42 patients underwent UAE for myoma or adenomyosis. Of these, 21 received an intravenous opioid (pethidine) and a nonsteroidal anti-inflammatory drug (group A), and 21 received an additional transdermal fentanyl patch (group B). Pain perception levels were established verbally on a 0-10 scale during the 24-hour period following UAE. Differences in pain trends, mean dose of intravenous pethidine, and adverse effects were compared between the two groups. Pain perception was most severe at 6 hours after UAE and the mean pain level of group B at that time was 6.3 ± 0.7, which was significantly lower than that of group A, 8.2 ± 0.7 (p 0.05), and no evidence of respiratory distress was demonstrated. The addition of a transdermal fentanyl patch to intravenous analgesics is effective in reducing post-embolization pain during the 24-hour period after UAE.

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... is used to evaluate the: bladder seminal vesicles prostate Transrectal ultrasound, a special study usually done to provide detailed evaluation of the prostate gland, involves inserting a specialized ultrasound transducer into ...

Obstetrical Ultrasound

Science.gov (United States)

... heartbeat can be seen as an ongoing ultrasound movie. Ultrasound devices also use Doppler, a special application ... the possible charges you will incur. Web page review process: This Web page is reviewed regularly by ...

Ultrasound imaging

International Nuclear Information System (INIS)

Wells, P.N.T.

1983-01-01

Ultrasound is a form of energy which consists of mechanical vibrations the frequencies of which are so high that they are above the range of human hearing. The lower frequency limit of the ultrasonic spectrum may generally be taken to be about 20 kHz. Most biomedical applications of ultrasound employ frequencies in the range 1-15 MHz. At these frequencies, the wavelength is in the range 1.5 - 0.1 mm in soft tissues, and narrow beams of ultrasound can be generated which propagate through such tissues without excessive attenuation. This chapter begins with brief reviews of the physics of diagnostic ultrasound pulse-echo imaging methods and Doppler imaging methods. The remainder of the chapter is a resume of the applications of ultrasonic imaging to physiological measurement

Automatic Ultrasound Scanning

DEFF Research Database (Denmark)

Moshavegh, Ramin

on the user adjustments on the scanner interface to optimize the scan settings. This explains the huge interest in the subject of this PhD project entitled “AUTOMATIC ULTRASOUND SCANNING”. The key goals of the project have been to develop automated techniques to minimize the unnecessary settings...... on the scanners, and to improve the computer-aided diagnosis (CAD) in ultrasound by introducing new quantitative measures. Thus, four major issues concerning automation of the medical ultrasound are addressed in this PhD project. They touch upon gain adjustments in ultrasound, automatic synthetic aperture image...

Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy.

Science.gov (United States)

Hynynen, Kullervo; Jones, Ryan M

2016-09-07

Focused ultrasound offers a non-invasive way of depositing acoustic energy deep into the body, which can be harnessed for a broad spectrum of therapeutic purposes, including tissue ablation, the targeting of therapeutic agents, and stem cell delivery. Phased array transducers enable electronic control over the beam geometry and direction, and can be tailored to provide optimal energy deposition patterns for a given therapeutic application. Their use in combination with modern medical imaging for therapy guidance allows precise targeting, online monitoring, and post-treatment evaluation of the ultrasound-mediated bioeffects. In the past there have been some technical obstacles hindering the construction of large aperture, high-power, densely-populated phased arrays and, as a result, they have not been fully exploited for therapy delivery to date. However, recent research has made the construction of such arrays feasible, and it is expected that their continued development will both greatly improve the safety and efficacy of existing ultrasound therapies as well as enable treatments that are not currently possible with existing technology. This review will summarize the basic principles, current statures, and future potential of image-guided ultrasound phased arrays for therapy.

Curcumin loaded chitin nanogels for skin cancer treatment via the transdermal route.

Science.gov (United States)

Mangalathillam, Sabitha; Rejinold, N Sanoj; Nair, Amrita; Lakshmanan, Vinoth-Kumar; Nair, Shantikumar V; Jayakumar, Rangasamy

2012-01-07

In this study, curcumin loaded chitin nanogels (CCNGs) were developed using biocompatible and biodegradable chitin with an anticancer curcumin drug. Chitin, as well as curcumin, is insoluble in water. However, the developed CCNGs form a very good and stable dispersion in water. The CCNGs were analyzed by DLS, SEM and FTIR and showed spherical particles in a size range of 70-80 nm. The CCNGs showed higher release at acidic pH compared to neutral pH. The cytotoxicity of the nanogels were analyzed on human dermal fibroblast cells (HDF) and A375 (human melanoma) cell lines and the results show that CCNGs have specific toxicity on melanoma in a concentration range of 0.1-1.0 mg mL(-1), but less toxicity towards HDF cells. The confocal analysis confirmed the uptake of CCNGs by A375. The apoptotic effect of CCNGs was analyzed by a flow-cytometric assay and the results indicate that CCNGs at the higher concentration of the cytotoxic range showed comparable apoptosis as the control curcumin, in which there was negligible apoptosis induced by the control chitin nanogels. The CCNGs showed a 4-fold increase in steady state transdermal flux of curcumin as compared to that of control curcumin solution. The histopathology studies of the porcine skin samples treated with the prepared materials showed loosening of the horny layer of the epidermis, facilitating penetration with no observed signs of inflammation. These results suggest that the formulated CCNGs offer specific advantage for the treatment of melanoma, the most common and serious type of skin cancer, by effective transdermal penetration.

Transdermal rotigotine causes impulse control disorders in patients with restless legs syndrome.

Science.gov (United States)

Schreglmann, S R; Gantenbein, A R; Eisele, G; Baumann, C R

2012-02-01

Dopaminergic drugs are the mainstay of treatment for restless legs syndrome (RLS). We analyzed the frequency and clinical characteristics of impulse control disorders (ICD) in patients with RLS on transdermal rotigotine treatment. Retrospective case series at a university movement disorder clinic (n = 28, 17 women). Symptoms of ICD were assessed via detailed history taking and scoring with the Zurich Screening Questionnaire for ICD (ZICD) prior to and after initiation of treatment. None of the patients had a history of ICD prior to treatment. Baseline mean scores for patients who did (8.0 ± 2.5) and did not (6.2 ± 2.7) develop ICD under treatment did not differ. Six male patients (21%) developed various symptoms of ICD (mean ZICD scores 20.7 ± 10.2) on rotigotine treatment (mean dose: 3.8 mg/d), including binge eating, hypersexuality, compulsive shopping, pathological gambling, and punding, equaling a prevalence rate of 21%. Also in the non-ICD group, ZICD scores increased (7.5 ± 2.8). This is the first report of ICD in patients treated with transdermal rotigotine for RLS. In contrast to literature, even low doses of rotigotine (mean 3.8 mg/d) can cause ICD. Therefore every prescribing physician should be aware that ICD may emerge in both RLS and PD patients on any dopaminergic treatment, and should actively ask for such symptoms. The ZICD questionnaire not only replicated the findings of detailed history taking but also showed an increased tendency towards impulsive behaviour in subjects that did not develop ICD. Copyright © 2011 Elsevier Ltd. All rights reserved.

Predictors of detection of alcohol use episodes using a transdermal alcohol sensor.

Science.gov (United States)

Barnett, Nancy P; Meade, E B; Glynn, Tiffany R

2014-02-01

The objective of this investigation was to establish the ability of the Secure Continuous Remote Alcohol Monitoring (SCRAM) alcohol sensor to detect different levels of self-reported alcohol consumption, and to determine whether gender and body mass index, alcohol dependence, bracelet version, and age of bracelet influenced detection of alcohol use. Heavy drinking adults (N = 66, 46% female) wore the SCRAM for 1-28 days and reported their alcohol use in daily Web-based surveys. Participant reports of alcohol use were matched with drinking episodes identified from bracelet readings. On days when bracelets were functional, 690 drinking episodes were reported and 502 of those episodes (72.8%) were detected using sensor data. Using generalized estimating equations, we found no gender differences in detection of reported drinking episodes (77% for women, 69% for men). In univariate analyses, at the level of fewer than 5 drinks, women's episodes were more likely to be detected, likely because of the significantly higher transdermal alcohol concentration levels of these episodes, whereas at the level of 5 or more drinks, there was no gender difference in detection (92.6% for women, 93.4% for men). In multivariable analyses, no variables other than number of drinks significantly predicted alcohol detection. In summary, the SCRAM sensor is very good at detecting 5 or more drinks; performance of the monitor below this level was better among women because of their higher transdermal alcohol concentration levels. Individual person characteristics and bracelet features were not related to detection after number of drinks was included. Minimal bracelet malfunctions were noted.

Ultrasound -- Pelvis

Medline Plus

Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician Resources Professions Site Index A-Z Ultrasound - Pelvis Ultrasound imaging ...

Prostate Ultrasound

Medline Plus

Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician Resources Professions Site Index A-Z Ultrasound - Prostate Ultrasound of ...

Improving arteriovenous fistula patency: Transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation.

Science.gov (United States)

MacAskill, Mark G; Watson, David G; Ewart, Marie-Ann; Wadsworth, Roger; Jackson, Andrew; Aitken, Emma; MacKenzie, Graeme; Kingsmore, David; Currie, Susan; Coats, Paul

2015-08-01

Creation of an autologous arteriovenous fistula (AVF) for vascular access in haemodialysis is the modality of choice. However neointimal hyperplasia and loss of the luminal compartment result in AVF patency rates of ~60% at 12months. The exact cause of neointimal hyperplasia in the AVF is poorly understood. Vascular trauma has long been associated with hyperplasia. With this in mind in our rabbit model of AVF we simulated cannulation autologous to that undertaken in vascular access procedures and observed significant neointimal hyperplasia as a direct consequence of cannulation. The neointimal hyperplasia was completely inhibited by topical transdermal delivery of the non-steroidal anti-inflammatory (NSAID) diclofenac. In addition to the well documented anti-inflammatory properties we have identified novel anti-proliferative mechanisms demonstrating diclofenac increases AMPK-dependent signalling and reduced expression of the cell cycle protein cyclin D1. In summary prophylactic transdermal delivery of diclofenac to the sight of AVF cannulation prevents adverse neointimal hyperplasic remodelling and potentially offers a novel treatment option that may help prolong AVF patency and flow rates. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... needles are used to extract a sample of cells from organs for laboratory testing. Doppler ultrasound images ... ultrasound, measures the direction and speed of blood cells as they move through vessels. The movement of ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... insertion. top of page How does the procedure work? Ultrasound imaging is based on the same principles ... modality for the diagnosis and monitoring of pregnant women and their unborn babies. Ultrasound provides real-time ...

Prostate Ultrasound

Medline Plus

Full Text Available ... top of page What are the benefits vs. risks? Benefits Ultrasound is widely available, easy-to-use ... procedures such as needle biopsies and fluid aspiration. Risks For standard diagnostic ultrasound , there are no known ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... the procedure? In women, a pelvic ultrasound is most often performed to evaluate the: uterus cervix ovaries ... page How is the procedure performed? Transabdominal: For most ultrasound exams, you will be positioned lying face- ...

Prostate Ultrasound

Medline Plus

Full Text Available ... to-use and less expensive than other imaging methods. Ultrasound imaging uses no ionizing radiation. Ultrasound scanning ... radiation oncology provider in your community, you can search the ACR-accredited facilities database . This website does ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... diagnose symptoms experienced by women such as: pelvic pain abnormal vaginal bleeding other menstrual problems Ultrasound exams ... pelvic ultrasound can help evaluate: pelvic masses pelvic pain ambiguous genitalia and anomalies of pelvic organs early ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... size, shape and consistency (whether the object is solid or filled with fluid). In medicine, ultrasound is ... ultrasound, measures the direction and speed of blood cells as they move through vessels. The movement of ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... by women such as: pelvic pain abnormal vaginal bleeding other menstrual problems Ultrasound exams also help identify: ... fibroids cancer, especially in patients with abnormal uterine bleeding Some physicians also use 3-D ultrasound or ...

Prostate Ultrasound

Medline Plus

Full Text Available ... those sound waves to create an image. Ultrasound examinations do not use ionizing radiation (as used in ... abnormal masses, such as tumors. In an ultrasound examination, a transducer both sends the sound waves into ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... There are three types of pelvic ultrasound: abdominal, vaginal (for women), and rectal (for men). These exams ... are three types of pelvic ultrasound: abdominal ( transabdominal ) vaginal ( transvaginal / endovaginal ) for women rectal ( transrectal ) for men ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... object is solid or filled with fluid). In medicine, ultrasound is used to detect changes in appearance, ... have special pediatric considerations. The teddy bear denotes child-specific content. Related Articles and Media Sonohysterography Ultrasound - ...

Prostate Ultrasound

Medline Plus

Full Text Available ... and produces pictures of the inside of the body using sound waves. Ultrasound imaging, also called ultrasound ... from the probe through the gel into the body. The transducer collects the sounds that bounce back ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... and produces pictures of the inside of the body using sound waves. Ultrasound imaging, also called ultrasound ... from the probe through the gel into the body. The transducer collects the sounds that bounce back ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... investigation of the uterine cavity . Three-dimensional (3-D) ultrasound permits evaluation of the uterus and ovaries ... abnormal uterine bleeding Some physicians also use 3-D ultrasound or sonohysterography for patients with infertility. In ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... insertion. top of page How does the procedure work? Ultrasound imaging is based on the same principles ... have special pediatric considerations. The teddy bear denotes child-specific content. Related Articles and Media Sonohysterography Ultrasound - ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... Imaging? Ultrasound waves are disrupted by air or gas; therefore ultrasound is not an ideal imaging technique ... page Additional Information and Resources RTAnswers.org Radiation Therapy for Gynecologic Cancers Radiation Therapy for Prostate Cancer ...

Prostate Ultrasound

Medline Plus

Full Text Available ... of page What will I experience during and after the procedure? Ultrasound exams in which the transducer ... in the sperm or urine following the procedure. After an ultrasound examination, you should be able to ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... Ultrasound is the preferred imaging modality for the diagnosis and monitoring of pregnant women and their unborn ... sexes without x-ray exposure. Risks For standard diagnostic ultrasound , there are no known harmful effects on ...

Prostate Ultrasound

Medline Plus

Full Text Available ... ultrasound images are captured in real-time, they can show the structure and movement of the body's ... Because ultrasound provides real-time images, it also can be used to guide procedures such as needle ...

Prostate Ultrasound

Medline Plus

Full Text Available ... patient. Because ultrasound images are captured in real-time, they can show the structure and movement of ... test result. difficulty urinating. Because ultrasound provides real-time images, it also can be used to guide ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... patient. Because ultrasound images are captured in real-time, they can show the structure and movement of ... help to distract the child and make the time pass quickly. The ultrasound exam room may have ...

Prostate Ultrasound

Medline Plus

Full Text Available ... Ultrasound provides real-time imaging, making it a good tool for guiding minimally invasive procedures such as ... bowel (rectum) removed during prior surgery are not good candidates for ultrasound of the prostate gland because ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... image. Ultrasound examinations do not use ionizing radiation (as used in x-rays ), thus there is no ... structure and movement of the body's internal organs, as well as blood flowing through blood vessels. Ultrasound ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... and development of an embryo or fetus during pregnancy. See the Obstetrical Ultrasound page for more information . ... object is solid or filled with fluid). In medicine, ultrasound is used to detect changes in appearance, ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... menstrual problems Ultrasound exams also help identify: palpable masses such as ovarian cysts and uterine fibroids ovarian ... In children, pelvic ultrasound can help evaluate: pelvic masses pelvic pain ambiguous genitalia and anomalies of pelvic ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... most ultrasound exams, you will be positioned lying face-up on an examination table that can be ... region of the prostate. A biopsy will add time to the procedure. If a Doppler ultrasound study ...

Ultrasound -- Pelvis

Medline Plus

Full Text Available ... ultrasound: abdominal, vaginal (for women), and rectal (for men). These exams are frequently used to evaluate the ... vaginal ( transvaginal / endovaginal ) for women rectal ( transrectal ) for men A Doppler ultrasound exam may be part of ...