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Tzu-Hao Huang,1 Chih-Jung Chen,2– 4 Hsin-Chia Angela Lin,1 Chun-Han Chen,1,* Jia-You Fang5– 7,* 1Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan; 2Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 3School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 4Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 5Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; 6Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; 7Department of Anesthesiology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan*These authors contributed equally to this workCorrespondence: Chun-Han Chen, Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, 6, W. Sec., Jiapu Road, Puzih City, Chiayi County, 61363, Taiwan, Tel +886-5-3621000 ext. 3821, Fax +886-5-3623002, Email chen5746@cgmh.org.tw Jia-You Fang, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan, 333, Taiwan, Tel +886-3-2118800, Fax +886-3-2118236, Email fajy@mail.cgu.edu.twPurpose: Morbid obesity and its related metabolic syndrome are an important health issue. Recently, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) have accounted for the most popular bariatric surgeries. Valsartan (VST) is a common hypertension drug, and nano-carriers can increase its solubility and bioavailability. This study aims to explore the nano-VST formula in bariatric surgery subjects.Methods: High-fat fed animals were used as obese models. Operations were performed according to a standardized protocol. The drug was administrated by gavage, and blood samples were taken by serial tail vein sampling. Caco-2 cells were used for examining cell viability and drug uptake. A self-nano-emusifying drug delivery system (SNEDDS) formula was composed of sefsol-218, RH-40 and propylene glycol by a specified ratio, while high-performance liquid chromatography (HPLC) was used for determining drug concentrations.Results: Post-operatively, subjects that underwent RYGB lost more body weight compared to the SG group. The SNEDDS did not exhibit cytotoxicity after adequate dilution, and the cytotoxicity was not related to VST dose. A better cellular uptake of SNEDDS was observed in vitro. The SNEDDS formula achieved a diameter of 84 nm in distilled water and 140 nm in simulated gastric fluid. In obese animals, the maximum serum concentration (Cmax) of VST was increased 1.68-folds by SNEDDS. In RYGB with SUS, the Cmax was reduced to less than 50% of the obese group. SNEDDS increased the Cmax to 3.5 folds higher than SUS and resulted in 3.28-folds higher AUC0-24 in the RYGB group. Fluorescence imaging also confirmed a stronger signal of SNEDDS in the gastrointestinal mucosa. SNEDDS accumulated a higher drug concentration than suspension alone in the liver of the obese group.Conclusion: SNEDDS could reverse the VST malabsorption in RYGB. Further studies are mandatory to clarify post-SG change of drug absorption.Keywords: gastric bypass, sleeve gastrectomy, valsartan, nano-drug delivery system

To investigate whether endothelial nitric oxide synthase (Genotyping for theThe genotype and allele frequency distributions ofThe T allele could be a risk factor for PAH in newborns with CHD in South Fujian through decreased levels of nitric oxide production by the endothelium.

Introduction: The use of herbal compounds in cancer therapy has great potential to promote the efficacy of current cancer therapeutic strategies. Herbal compounds were successfully reported to enhance tumor cells sensitization to the action of chemo-, hormonal- and gene-therapeutic agents via different mechanisms. Herbal ingredients can affect different signaling pathways, reduce the toxic side effects or inhibit the efflux of anticancer drugs.Areas covered: This review will discuss the delivery of herbal compounds with other cancer treatments such as hormonal, small molecule inhibitors and inorganic hybrids to tumor cells. An overview of physicochemical properties of herbal components that require intelligent design of combo-nanomedicines for efficient co-delivery of those herbal-derived and other anticancer agents was discussed. Nanocarriers provide various benefits to overcome the shortcomings of the encapsulated herbal compounds including improved solubility, increased stability and enhanced tumor targeting. Different nanocarrier systems were the focus of this review.Expert opinion: Multifunctional nanocarrier systems encapsulating herbal and different anticancer drugs showed to be a wonderful approach in the treatment of cancer enabling the co-delivery of anticancer drugs with versatile modes of action in an accurate manner in an attempt to enhance the efficacy, benefit from the synergism between the drugs as well as to minimize the development of multi-drug resistance. The main challenge point is the early detection and management of any developed adverse effect.

Redox and ultrasonic responsive copolymers MPEG-S-S-P(αN3CL-g-ibu7POSS)x-r-PCLy bearing grafted hydrophobic polyhedral oligomeric silsesquioxane (POSS) were synthesized through a click reaction between MPEG-S-S-P(αN3CL)x-r-PCLy and alkynyl POSS. The morphology revealed that the copolymers underwent micellization or dissociation transitions in response to the reducing agent and ultrasound treatment. The release rate could be substantially increased and adjusted remotely under ultrasound radiation in the presence of dithiothreitol. The nanoparticles exhibited slight toxicity against HeLa cells. After high-intensity focused ultrasound (HIFU) irradiation, DOX-loaded micelles effectively inhibited the proliferation of HeLa cells with a half-maximal inhibitory concentration of 1.1 μg mL−1, and enhanced cellular uptake.

Background It is important to explore the interaction between antibacterial nanoparticles and microbes for understanding bactericidal activity and developing novel applications. It is possible that the nanoparticulate size can govern the antibacterial potency. Purpose The purpose of this study was to evaluate the antimicrobial and antibiofilm properties of cetylpyridinium chloride (CPC)-decorated nanoemulsions against methicillin-resistant Staphylococcus aureus (MRSA). Methods The droplet size could be adjusted by varying the percentage of squalene, the main ingredient of the oily core. Results We fabricated cationic nanoemulsions of three different sizes, 55, 165, and 245 nm. The nanoemulsions showed greater storage stability than the self-assembled CPC micelles. The tested nanoemulsions exhibited more antimicrobial activity against Gram-positive bacteria than Gram-negative bacteria and fungi. The killing of MRSA was mainly induced by direct cell-membrane damage. This rupture led to the leakage of cytoplasmic DNA and proteins. The nanoemulsions might also degrade the DNA helix and disturb protein synthesis. The proteomic analysis indicated the significant downregulation of DNA-directed RNA polymerase (RNAP) subunits β and β'. The antibacterial effect of nanoemulsions increased with decreasing droplet size in the biofilm MRSA but not planktonic MRSA. The small-sized nanoemulsions had potent antibiofilm activity that showed a colony-forming unit (CFU) reduction of 10-fold compared with the control. The loss of total DNA concentration also negatively correlated with the nanoemulsion size. Conclusion The present report established a foundation for the development of squalene@CPC nanosystems against drug-resistant S. aureus.

Introduction: The ablative laser can be used as an effective approach for enhancing drug permeation via the skin. The enhancement mechanisms of laser-assisted drug permeation are the direct ablation of the superficial skin, optical breakdown by a photomechanical wave, and a photothermal effect. Areas covered: This review describes the development of laser-assisted drug delivery in the recent 5 years. This review systematically introduces the concepts and enhancement mechanisms of the technique, highlighting the potential of the laser approach for increasing drug absorption via the skin. A recent advance of this approach is the use of fractional laser offering limited skin damage and short recovery time. Another sign of progress regarding laser-assisted drug delivery in the recent 5 years is the clinical trials for treating various dermatological disorders. Expert opinion: The potential use of the laser-assisted approach affords a novel treatment for topical drug application with significant efficacy. Although many clinical studies have been performed, further studies using a large group for patients are needed to confirm and clarify the findings in the in vitro or animal experiments. The laser-assisted delivery should be optimized to achieve skin targeting without the risk of diffusion into circulation.

Aim This paper reports on the incorporation of oleic acid (OA) within nanostructured lipid carriers (OA-NLC) to improve the anti-inflammatory effects in the presence of albumin. Materials and methods NLCs produced via hot high-shear homogenization/ultrasonication were characterized in terms of particle size, zeta potential, and toxicity. We examined the effects of OA-NLC on neutrophil activities. Dermatologic therapeutic potential was also elucidated by using a murine model of leukotriene B4-induced skin inflammation. Results In the presence of albumin, OA-NLC but not free OA inhibited superoxide generation and elastase release. Topical administration of OA-NLC alleviated neutrophil infiltration and severity of skin inflammation. Conclusion OA incorporated within NLC can overcome the interference of albumin, which would undermine the anti-inflammatory effects of OA. OA-NLC has potential therapeutic effects in topical ointments.

Psoriasis is an autoimmune skin disease characterized by red plaques with silver or white multilayered scales with a thickened acanthotic epidermis. Using mouse models of cutaneous inflammation, IL-23/Th17 was identified to have a potential key role in psoriasis. New treatments to slow this inflammatory skin disorder are urgently needed. To aid their discovery, a psoriasis animal model mimicking human psoriasis is urgently needed for their early preclinical evaluation. Areas covered: The authors review animal models of psoriasis and analyze the features and molecular mechanisms involved in these mouse models. The application of various mouse models of psoriasis for drug discovery and development has also been reviewed and the possible molecular targets in psoriasis for future anti-psoriatic drug design is discussed. Expert opinion: So far, it has been difficult to create an animal model that exactly simulates a human disease or condition. The xenotransplantation model is regarded as the closest to incorporating the complete genetic, phenotypic, and immunopathogenic processes of psoriasis. However, the imiquimod (IMQ)-induced model is the most prevalent among psoriatic mouse models due to its ease of use, convenience, and low cost. Further efforts to develop psoriasis-like skin models in mice are needed for the study and treatment of this complex disease.

Ryk is a member of the receptor tyrosine kinase (RTK) family of proteins that control and regulate cellular processes. It is distinguished by binding Wnt ligands and having no detectable intrinsic protein tyrosine kinase activity suggesting Ryk is a pseudokinase. Here, we show an essential role for Ryk in directing morphogenetic events required for normal cardiac development through the examination of Ryk-deficient mice. We employed vascular corrosion casting, vascular perfusion with contrast dye, and immunohistochemistry to characterize cardiovascular and pharyngeal defects in Ryk-/- embryos. Ryk-/- mice exhibit a variety of malformations of the heart and outflow tract that resemble human congenital heart defects. This included stenosis and interruption of the aortic arch, ventriculoarterial malalignment, ventricular septal defects and abnormal pharyngeal arch artery remodelling. This study therefore defines a key intersection between a subset of growth factor receptors involved in planar cell polarity signalling, the Wnt family and mammalian cardiovascular development.

Chun-Han Chen,1,2,* Tse-Hung Huang,3–5,* Ahmed O Elzoghby,6,7 Pei-Wen Wang,8 Chia-Wen Chang,9 Jia-You Fang9–12 1Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kweishan, Taoyuan, 3Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, 4School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, 5School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; 6Cancer Nanotechnology Research Laboratory (CNRL), 7Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 8Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 9Pharmaceutics Laboratory, Graduate Institute of Natural Products, 10Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, 11Department of Anesthesiology, Chang Gung Memorial Hospital, 12Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan *These authors contributed equally to this work Abstract: The increasing death rate caused by drug overdose points to an urgent demand for the development of novel detoxification therapy. In an attempt to detoxify tricyclic antidepressant overdose, we prepared a lipid nanoemulsion, called squarticles, as the nanoantidote. Squalene was the major lipid matrix of the squarticles. Here, we present the animal study to investigate both the pharmacokinetic and pharmacodynamic effects of squarticles on amitriptyline intoxication. The anionic and cationic squarticles had average diameters of 97 and 122 nm, respectively. Through the entrapment study, squarticles could intercept 40%–50% of the amitriptyline during 2 h with low leakage after loading into the nanoparticles. The results of isothermal titration calorimetry demonstrated greater interaction of amitriptyline with the surface of anionic squarticles (Ka =28,700) than with cationic ones (Ka =5,010). Real-time imaging showed that intravenous administration of anionic squarticles resulted in a prolonged retention in the circulation. In a rat model of amitriptyline poisoning, anionic squarticles increased the plasma drug concentration by 2.5-fold. The drug uptake in the highly perfused organs was diminished after squarticle infusion, indicating the lipid sink effect of bringing the entrapped overdosed drug in the tissues back into circulation. In addition, the anionic nanosystems restored the mean arterial pressure to near normal after amitriptyline injection. The survival rate of overdosed amitriptyline increased from 25% to 75% by treatment with squarticles. Our results show that the adverse effects of amitriptyline intoxication could be mitigated by administering anionic squarticles. This lipid nanoemulsion is a potent antidote to extract amitriptyline and eliminate it. Keywords: squarticles, squalene, amitriptyline, overdose, antidote, pharmacokinetics

Ching-Yun Hsu,1,2,* Shih-Chun Yang,3,4,* Calvin T Sung,5 Yi-Han Weng,4 Jia-You Fang2,4,6,7 1Department of Nutrition and Health Sciences, 2Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, 3Department of Cosmetic Science, Providence University, Taichung, 4Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taiwan; 5School of Medicine, University of California, Riverside, CA, USA; 6Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, 7Department of Anesthesiology, Chang Gung Memorial Hospital, Kweishan, Taiwan *These authors contributed equally to this work Abstract: Pathogens usually invade hair follicles when skin infection occurs. The accumulated bacteria in follicles are difficult to eradicate. The present study aimed to assess the cutaneous and follicular delivery of chloramphenicol (Cm)-loaded liposomes and the antibacterial activity of these liposomes against methicillin-resistant Staphylococcus aureus (MRSA). Skin permeation was conducted by in vitro Franz diffusion cell. The anti-MRSA potential was checked using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), a well diffusion test, and intracellular MRSA killing. The classic, dimyristoylphosphatidylcholine (DMPC), and deoxycholic acid (DA) liposomes had a vesicle size of 98, 132, and 239 nm, respectively. The incorporation of DMPC or DA into the liposomes increased the bilayer fluidity. The malleable vesicles containing DMPC and DA showed increased follicular Cm uptake over the control solution by 1.5- and 2-fold, respectively. The MIC and MBC of DA liposomes loaded with Cm were 62.5 and 62.5–125 µg/mL, comparable to free Cm. An inhibition zone about 2-fold higher was achieved by DA liposomes as compared to the free control at a Cm dose of 0.5 mg/mL. DA liposomes also augmented antibacterial activity on keratinocyte-infected MRSA. The deformable liposomes had good biocompatibility against keratinocytes and neutrophils (viability >80%). In vivo administration demonstrated that DA liposomes caused negligible toxicity on the skin, based on physiological examination and histology. These data suggest the potential application of malleable liposomes for follicular targeting and the treatment of MRSA-infected dermatologic conditions. Keywords: chloramphenicol, malleable liposomes, deoxycholic acid, hair follicle, MRSA, antibacterial activity

Remodelling of lymphatic vessels in tumours facilitates metastasis to lymph nodes. The growth factors VEGF-C and VEGF-D are well known inducers of lymphatic remodelling and metastasis in cancer. They are initially produced as full-length proteins requiring proteolytic processing in order to bind VEGF receptors with high affinity and thereby promote lymphatic remodelling. The fibrinolytic protease plasmin promotes processing of VEGF-C and VEGF-D in vitro, but its role in processing them in cancer was unknown. Here we explore plasmin’s role in proteolytically activating VEGF-D in vivo, and promoting lymphatic remodelling and metastasis in cancer, by co-expressing the plasmin inhibitor α2-antiplasmin with VEGF-D in a mouse tumour model. We show that α2-antiplasmin restricts activation of VEGF-D, enlargement of intra-tumoural lymphatics and occurrence of lymph node metastasis. Our findings indicate that the fibrinolytic system influences lymphatic remodelling in tumours which is consistent with previo...

Codrug or mutual prodrug is a drug design approach to chemically bind two or more drugs to improve therapeutic efficiency or decrease adverse effects. The codrug can be cleaved in the body to generate parent actives. The codrug itself can be inactive, less active, or more active than the parent agents. It has been demonstrated that codrugs possess some benefits over conventional drugs, including enhanced solubility, increased permeation for passing across biomembranes, prolonged half-life for extending the therapeutic period, and reduced toxicity.This review article describes the history, design strategy, and potential applications of codrugs. Codrugs are predominantly used to treat some conditions such as neurodegenerative, cardiovascular, cancerous, infectious, and inflammatory disorders. Many codrugs are developed to increase lipophilicity for better transport into/across biomembranes, especially the skin and cornea. A targeted delivery of codrugs to specific tissues or organs thus can be achieved to promote bioavailability. The chemical and enzymatic hydrolysis, bioactivity, and pharmacokinetics of codrugs are systematically introduced in this review.Additional profiles pertaining to clinical trials will support further applicability of codrug therapy. Caution should be used in optimizing the benefits of codrugs to ensure a balance between damage or toxicity and the effectiveness of delivery enhancement.

We investigated the effects of different raising systems on growth performance, lipid deposition and meat quality traits of chickens. The chickens were raised for 28 days and then randomly assigned into three raising systems with similar body weight (BW) as follows: indoor caged, indoor floor pens and free-range system. They were sacrificed and analysed after 112 days. The raising system had no significant effect on BW and daily weight gain (P > 0.05), but had a significant effect on male thigh intramuscular fat (IMF) and female abdominal fat content (PAF) content (P < 0.05). The expression of hepatic fatty acid synthase (FAS) mRNA level in free-range raising system was significantly lower than that of caged indoor raising systems (P < 0.05). The meat quality (ΔpH, drip loss, shear force and fibre traits) was largely affected by the raising system (P < 0.05). In conclusion, the data indicated that the free-range raising system could significantly reduce thigh IMF content and hepatic FAS expression, conseq...

The systematic position of the genus Bryhnia Kaurin has been problematic and remains unsettled. A phylogenetic analysis of Bryhnia and closely related genera, based on the nuclear marker ITS1–5·8S–ITS2 and the plastid markers rpl16, trnG, and trnL–F, was carried out to clarify their relationships and systematic positions. The phylogenetic trees generated from Maximum parsimony and Bayesian analyses show that Bryhnia s.s., represented by B. novae-angliae (Sull. & Lesq.) Grout, B. hultenii E.B.Bartram, and B. scabrida (Lindb.) Kaurin, forms a maximally supported clade nested within Brachythecium Schimp. ‘Bryhnia scabrida’ sensu Ignatov & Huttunen (2002) is Bryhnia brachycladula Cardot, and together they form a monophyletic group with Eurhynchiadelphus eustegia (Besch.) Ignatov & Huttunen and Myuroclada maximowiczii (G.G.Borshch.) Steere & W.B.Schofield. We propose the inclusion of the species currently recognized in Bryhnia in Brachythecium, with the transfer of Bryhnia brachycladula to the genus Myuroclada...

A new mononuclear eddy identification method based on sea level anomaly (SLA) data was developed and described in this study. To solve the multinuclear eddy problem, we employed two strategies to split the eddies into individual eddies: the closest angle and the closest distance strategies. Each strategy produces an eddy with only one SLA extremum. The splitting procedure is based on these strategies. No artificial threshold is needed with these strategies, but a threshold for strategy choice is required. The splitting strategies are adaptable to various identification methods. The examples indicate that the splitting procedure clearly captures the mixing of eddies. When applied to the global ocean, the proposed method obtained similar and more reasonable results. The splitting procedure is linear without any iteration; thus, it is very fast (the time complexity is O(N), where N is the number of multinuclear eddy pixels). In statistics, the proposed method can identify approximately 30-40% more eddies than the multinuclear eddy method.

The Thousand-Island Lake (Zhejiang Province, China) was artificially isolated 50 years ago and provides an interesting model for investigating the impact of fragmentation on the spatial genetic structure in plant populations. Using variation from inter-simple sequence repeat markers and DNA sequences in two moss species with contrasting reproductive strategies, Hypnum plumaeforme and Pogonatum inflexum, we investigate the effect of sexual and asexual reproduction on molecular diversity and spatial genetic structure in this fragmented landscape. In H. plumaeforme, which mostly reproduces asexually, genetic diversity of island populations was significantly higher than that of lakeside populations. In the frequently fertile P. inflexum, conversely, genetic diversity was not significantly different between island and lakeside populations. Furthermore, a clear island versus lakeshore structure emerged from the spatial analysis of genetic variation in H. plumaeforme, but not in P. inflexum. We conclude that dif...

A new moss species, Homaliodendron pulchrum, from China, is delimited by its distinct morphology and biogeography. The new species has oblong–spathulate to obovate leaves and an indistinct double costa, which is unique within the genus. Distribution of this new species is restricted to three localities in southwestern and southern China. The new species is described and illustrated and a key to the species of Homaliodendron in Eastern Asia is provided. The systematic position of H. pulchrum is revealed to be sister to H. montagneanum by molecular evidence based on the parsimony and maximum likelihood analyses of nad5 and rps4 sequences.

(2009). The identities of Meteorium undulifolium and M. balansaeanum (Meteoriaceae, Bryopsida) Journal of Bryology: Vol. 31, No. 4, pp. 279-282.

The aim of this work was to evaluate the use of Pluronic F127 (PF) hydrogels incorporating liposomes and/or grafted with alginate (AP) for the parenteral delivery of cisplatin. The physicochemical properties such as scanning electron microscopy (SEM), polarity and sol-gel transition temperature, as well as in vitro drug release of developed hydrogels were examined. The sol-gel temperature of PF, PF with liposomes and AP was 26.4, 19.7 and 26.6 degrees C, respectively. A hydrogel with stronger strength was obtained by alginate coupling (AP) according to SEM images and viscosity kinetics as compared to PF. Both liposomes and hydrogels could sustain the release of cisplatin to a certain level. The drug release from the vehicles decreased in the order of PFliposomesor = APor = PF/liposomesAP/liposomes. The burst release effect of cisplatin was inhibited when using the AP/liposomes composite system as the vehicle. Formulations were administered intratumorally in melanoma-bearing mice. The respective liposomes or hydrogels did not increase cisplatin accumulation in melanomas compared to the control (aqueous solution). PF/liposomes and AP/liposomes, respectively, increased cisplatin deposition by 2.5- and 4.4-fold. To our best of knowledge, the present work is the first report to investigate the drug delivery from PF-alginate conjugates.

New thermosensitive hydrogels of poly(N-isopropylacrylamide) (PNIPAAm) with chitosan (CPN) were prepared and evaluated for use in the delivery of the platinum drugs, cisplatin and carboplatin. The effects of polymers containing different ratios of chitosan on the physicochemical and drug release characteristics were examined. The sol-gel transition temperature of the hydrogels was determined by differential scanning calorimetry (DSC) and viscometry. Discrepancies in the transition temperature among the various polymer systems were more pronounced when determined by viscosity compared by DSC, with the CPN showing a higher transition temperature than PNIPAAm. The cross-sectional structure and surface topography of the hydrogels were examined by scanning electronic microscopy (SEM) and atomic force microscopy (AFM), respectively. The incorporation of chitosan further increased the entanglement of the hydrogel network. An increase in the chitosan ratio in the polymers (CPN-H) also increased the cross-linking structure. A smoother surface of hydrogel matrices was observed for CPN compared with PNIPAAm. All hydrogels tested significantly reduced drug release compared with an aqueous solution. The release rate of platinum drugs from PNIPAAm was retarded at the late stage. CPN matrices could continuously deliver platinum drugs during the experiment. The rate of release from CPN-H was generally slower than that from hydrogels and had a lower chitosan ratio (CPN-L), presumably due to the more-tortuous pathways in the hydrogels. Thermosensitive hydrogels like those prepared in this study may be a promising carrier for the delivery of platinum drugs, as the drug release can be controlled and sustained using CPN networks.

The random amplified polymorphic DNA (RAPD) technique was applied to assess genetic diversity and population structure of Brachythecium rivulare Schimp. (Brachytheciaceae) from Foping Nature Reserve (Qinling Mountain, China). Sixty individuals from five populations along an elevational gradient were investigated by RAPD profiles. Of the 61 primers screened, 12 primers amplified clear and reproducible bands. Using these primers, 122 discernible bands were generated with 82 (67.2%) being polymorphic. The results revealed a high level of genetic variation (percentage of polymorphic loci ranged from 53.28% to 63.11%; mean expected heterozygosity per locus ranged from 0.2024 to 0.2431; Shannon diversity index ranged from 0.3011 to 0.3582; genetic identity ranged from 0.8626 to 0.9395, with a mean of 0.9118; genetic distances ranged from 0.0624 to 0.1478, with a mean of 0.1008). Analysis of molecular variance showed that a large proportion of genetic variation (91.20%) resided within populations, where...

Tea polyphenols, including (+)-catechin, (-)-epicatechin, and (-)-epigallocatechin-3-gallate (EGCG), have been shown to possess potent antioxidant and anticancer activities. The aim of this study was to evaluate the possibility of using liposomes for the local delivery, including skin and tumor deposition, of these polyphenols. Liposomes containing egg phosphatidylcholine, cholesterol, or anionic species were prepared by a solvent evaporation method and then were subjected to a probe sonicator. The size, zeta potential and entrapment efficiency of these liposomal formulations were determined to provide correlations with results from a subsequent in vivo study. The release rate study showed that inclusion of an anionic species, such as deoxycholic acid (DA) or dicetyl phosphate (DP), increased the permeability of the lipid bilayers, leading to the rapid release of these formulations. No significant increase in skin deposition of catechins was observed after topical application of liposomes. On the other hand, a greater amount of catechins were delivered into the solid tumor by liposomes than by the aqueous solution. The drug release rate and vesicle size of liposomes may influence drug deposition in tumor tissues. The isomers, (+)-catechin and (-)-epicatechin, showed different physicochemical properties in liposomes and for local deposition in the skin and tumor. Finally, the presence of gallic acid ester in the structure of EGCG significantly increased the tissue uptake of catechins.

The application of lipid nano/submicron emulsions as topical drug carrier systems for the percutaneous absorption of flurbiprofen was investigated. The lipid emulsions were made up of isopropyl myristate (IPM), soybean oil, or coconut oil as the oil phase, egg lecithin as the predominant emulsifier, and double-distilled water as the external phase. Stearylamine (SA) and deoxycholic acid (DA) also were used to produce positively and negatively charged emulsions. To evaluate the physicochemical properties of the lipid emulsions, particle size by laser light scattering, the image of atomic force microscopy, and relaxation time values by Nuclear Magnetic Resonance (NMR) were determined. The in vitro permeation data showed that incorporation of SA significantly reduced the topical delivery of flurbiprofen. On the other hand, incorporation of DA exhibited no or a negligible effect on drug permeation. Enhancement of drug absorption was observed when adding oleic acid as part of the oil phase. The in vivo topical application of flurbiprofen from selected lipid emulsions showed a similar trend to the in vitro status. Furthermore, the intersubject variability was considerably reduced by lipid emulsions than by aqueous suspensions in both the in vitro and in vivo experiments. The irritant profiles of lipid emulsions showed that IPM elicited higher irritation than soybean oil. The incorporation of oleic acid also produced skin disruption. The results in the present study suggest the feasibility of lipid emulsions for the topical delivery of flurbiprofen.

Meteorium Dozy & Molk. (Meteoriaceae) is a genus of predominantly epiphytic, frequently pendent mosses widely distributed in tropical and subtropical Asia, Australasia, and Central and South Americ...

For more than 30 years techniques of delivering drugs through skin have been elaborated as clinically relevant methods to administer therapeutic agents. The great contributions of transdermal and topical administrations on clinical therapeutics are firmly based on their distinctive properties. Progress in new technologies and compound is continuously stimulating the growth and revolution of topical and transdermal administration. This review summarises recent developments in the design of formulations and the patent literature in the area of topical and transdermal drug delivery systems.

Nonivamide (NVA), sodium nonivamide acetate (SNA) and sodium nonivamide propionate (SNP) are analogues of Capsaicin (CAP). The structure and pungent property of NVA are similar to CAP. The solubilities of SNA in different pH value buffer solution were higher than that of NVA and CAP. For the NVA and SNA, the n-octanol/buffer partition coefficients decreased with increasing pH value. The fluxes of CAP and its analogues were determined using excised rat skin and the effect of pH was also investigated. The flux of NVA and SNA mixture was higher than individually NVA or SNA, and the ratio of 70:30 was a better choice. Sodium lauryl sulfate (SLS), an anionic surfactant, had significant effect on SNA skin permeation.

Chun-Han Chen,1,2 Cheng-Chih Chang,1 Tsung-Hsien Shih,2 Ibrahim A Aljuffali,3 Ta-Sen Yeh,4,5 Jia-You Fang6–8 1Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; 3Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 4Department of Surgery, Chang Gung Memorial Hospital, 5School of Medicine, College of Medicine, 6Pharmaceutics Laboratory, Graduate Institute of Natural Products, 7Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, 8Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan Abstract: Roux-en-Y gastric bypass (RYGB) is a popular surgery to reduce the body weight of obese patients. Although food intake is restricted by RYGB, drug absorption is also decreased. The purpose of this study was to develop novel self-nanoemulsifying drug delivery systems (SNEDDS) for enhancing the oral delivery of silymarin, which has poor water solubility. The SNEDDS were characterized by size, zeta potential, droplet number, and morphology. A technique of RYGB was performed in Sprague-Dawley rats. SNEDDS were administered at a silymarin dose of 600 mg/kg in normal and RYGB rats for comparison with silymarin aqueous suspension and polyethylene glycol (PEG) 400 solution. Plasma silibinin, the main active ingredient in silymarin, was chosen for estimating the pharmacokinetic parameters. SNEDDS diluted in simulated gastric fluid exhibited a droplet size of 190 nm with a spherical shape. The nanocarriers promoted silibinin availability via oral ingestion in RYGB rats by 2.5-fold and 1.5-fold compared to the suspension and PEG 400 solution, respectively. A significant double-peak concentration of silibinin was detected for RYGB rats receiving SNEDDS. Fluorescence imaging showed a deeper and broader penetration of Nile red, the fluorescence dye, into the gastrointestinal mucosa from SNEDDS than from PEG 400 solution. Histological examination showed that SNEDDS caused more minor inflammation at the gastrointestinal membrane as compared with that caused by PEG 400 solution, indicating a shielding of direct silymarin contact with the mucosa by the nanodroplets. SNEDDS generally showed low-level or negligible irritation in the gastrointestinal tract. Silymarin-loaded SNEDDS were successfully developed to improve the dissolution, permeability, and oral bioavailability of silymarin. To the best of our knowledge, this is the first investigation reporting the usefulness of SNEDDS for improving drug malabsorption elicited by gastric bypass surgery. Keywords: self-nanoemulsifying drug delivery system, Roux-en-Y gastric bypass, obesity, oral delivery, silymarin