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Asian Journal of Pharmaceutical Sciences 2018年第3期13卷 255-264页

作者： Jianhui Shu Jingjing Zhao Fang Guo Nanjing Sanhome Pharmaceutical CO. LTD.R&D Insititute

This study aimed to develop a suitable topical delivery system containing diethylene glycol monoethyl ether(DGME) for Loperamide hydrochloride(Lop). Two factors, three levels CentralComposite design were applied by generating a quadratic polynomial equation to form contour plots and response surface for prediction of responses as two selected independent variables with EtOH-DGME ratio and EtOH concentration. The response variables flux and skin retention were determined in in vitro hairless mouse skin model. The selected optimum formulation was evaluated for the skin transport characteristics by developing dermatokinetic analysis model and the results demonstrated DGME improved the delivery of Lop into skin deep layers, which was further confirmed by confocal laser scanning microscopy(CLSM)study. In vitro skin permeation was found to have triphasic correlation with plasma AUC in the in vivo pharmacokinetic study. The in vitro–in vivo correlation enabled the prediction of pharmacokinetic profile of Lop from in vitro permeation results. Therefore, the optimum formulation capable of enhancing Lop intracutaneous depot could be a candidate for topical delivery of Lop as analgesics.

关键词： Loperamide hydrochloride Topical delivery Skin retention In vitro–in vivo correlation

Protein trans-splicing based dual-vector delivery of the coagulation factor Ⅷ gene

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中国科学：生命科学英文版 2010年第6期53卷 683-689页

作者： ZHU FuXiang,LIU ZeLong,CHI XiaoYan & QU HuiGe Life Science College of Ludong University,Yantai 264025,China Life Science College of Ludong University Yantai China

A dual-vector system was explored for the delivery of the coagulation factor VIII gene,using intein-mediated protein trans-splicing as a means to produce intact functional factor VIII post-translationally.A pair of eukaryotic expression vectors,expressing Ssp DnaB intein-fused heavy and light chain genes of B-domain deleted factor VIII (BDD-FVIII),was *** transient co-transfection of the two vectors into 293 and COS-7 cells,the culture supernatants contained (137±23) and (109±22) ng mL–1 spliced BDD-FVIII antigen with an activity of (1.05±0.16) and (0.79±0.23) IU mL–1 for 293 and COS-7 cells,*** spliced BDD-FVIII was also detected in supernatants from a mixture of cells transfected with inteinfused heavy and light chain *** spliced BDD-FVIII protein bands from cell lysates were visualized by Western *** data demonstrated that intein could be used to transfer the split factor VIII gene and provided valuable information on factor VIII gene delivery by dual-adeno-associated virus in hemophilia A gene therapy.

关键词： intein protein trans-splicing coagulation factor VIII dual-vector gene delivery

Estimation of soil erosion in a rain shadow river basin in the southern Western Ghats, India using RUSLE and transport limited sediment delivery function

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International Soil and Water Conservation Research 2018年第2期6卷 111-122页

作者： Jobin Thomas Sabu Joseph KPThrivikramji EWRE Department of Civil EngineeringIndian Institute of Technology MadrasChennai600036Tamil NaduIndia Department of Environmental Sciences University of KeralaThiruvananthapuram695581KeralaIndia Center for Environment and Development Thiruvananthapuram695013KeralaIndia

Soil erosion and deposition in a tropical mountainous river basin, viz., Pambar River Basin (PRB), in a rain shadow region of the southern Western Ghats (India) were modelled using Revised Universal Soil Loss Equation (RUSLE) and transport limited sediment delivery (TLSD) function in GIS. Mean gross soil erosion in the basin is 11.70 t ha-1 yr-1, and is comparable with the results of previous soil erosion studies from the region. However, mean net soil erosion from the basin is 2.92 t ha-1 yr-1 only, which is roughly 25%of the gross soil erosion. Although natural vegetation belts show relatively higher gross- and net-soil erosion rates (mainly due to high LS and C factors), their sediment transport efficiency is remarkably less, compared to the land use/ land cover types with anthropogenic signatures (i.e., plantations and crop-lands). Despite the lesser amount of annual rainfall, the high rates of soil loss from the semi-arid areas of the basin might be the result of the poor protective vegetation cover as well as isolated high intensity rainfall events. The study highlights the significance of climate-specific plans for soil erosion manage-ment and conservation of the soil resources of the basins developed in rain shadow regions.

关键词： Soil erosion RUSLE Transport limited sediment delivery Rain shadow region Pambar River Basin Western Ghats

Enhanced transdermal delivery of meloxicam by nanocrystals: Preparation, in vitro and in vivo evaluation

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Asian Journal of Pharmaceutical Sciences 2018年第6期13卷 518-526页

作者： Qina Yu Xiying Wu Quangang Zhu Wei Wu Zhongjian Chen Ye Li Yi Lu Shanghai Dermatology Hospital Department of Pharmaceutics School of Pharmacy Fudan University Shaanxi Academy of Traditional Chinese Medicine

Meloxicam(MLX) is efficient in relieving pain and inflammatory symptoms, which, however, is limited by the poor solubility and gastrointestinal side effects. The objective of this study is to develop a nanocrystal formulation to enhance transdermal delivery of MLX. MLX nanocrystals were successfully prepared by the nanoprecipitation technique based on acidbase neutralization. With poloxamer 407 and Tween 80(80/20, w/w) as mixed stabilizers,MLX nanocrystals with particle size of 175 nm were obtained. The crystalline structure of MLX nanocrystals was confirmed by both differential scanning calorimetry and X-ray powder diffractometry. However, the nanoprecipitation process reduced the crystallinity of *** increased both in vitro and in vivo transdermal permeation of MLX compared with the solution and suspension counterparts. Due to the enhanced apparent solubility and dissolution as well as the facilitated hair follicular penetration, nanocrystals present a high and prolonged plasma MLX concentration. And 2.58-and 4.4-fold increase in AUC0 →2 4 h was achieved by nanocrystals comparing with solution and suspension, respectively. In conclusion, nanocrystal is advantageous for transdermal delivery of MLX.

关键词： Meloxicam Nanocrystals Transdermal delivery Nanoprecipitation Acid-base neutralization

Cyclodextrin/chitosan nanoparticles for oral ovalbumin delivery: Preparation, characterization and intestinal mucosal immunity in mice

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Asian Journal of Pharmaceutical Sciences 2019年第2期14卷 193-203页

作者： Muye He Chen Zhong Huibing Hu Yu Jin Yanzuo Chen Kaiyan Lou Feng Gao Department of Pharmaceutics School of Pharmacy East China University of Science and Technology Shanghai Key Laboratory of New Drug Design East China University of Science and Technology Shanghai Key Laboratory of Functional Materials Chemistry East China University of Science and Technology

A novel oral protein delivery system with enhanced intestinal penetration and improved antigen stability based on chitosan(CS) nanoparticles and antigen-cyclodextrin(CD) inclusion complex was prepared by a precipitation/coacervation method. Ovalbumin(OVA) as a model antigen was firstly encapsulated by cyclodextrin, either β-cyclodextrin( β-CD) or carboxymethyl-hydroxypropyl-β-cyclodextrin(CM-HP-β-CD) and formed OVA-CD inclusion complexes, which were then loaded to chitosan nanoparticles to form OVA loaded β-CD/CS or CM-HP-β-CD/CS nanoparticles with uniform particle size(836.3 and 779.2 nm, respectively) and improved OVA loading efficiency(27.6% and 20.4%, respectively). In vitro drug release studies mimicking oral delivery condition of OVA loaded CD/CS nanoparticles showed low initial releases at p H 1.2 for 2 h less than 3.0% and a delayed release which was below to 30% at p H 6.8 for further 72 h. More importantly, after oral administration of OVA loaded β-CD/CS nanoparticles to Balb/c mice, OVA-specific sIgA levels in jejunum of OVA loaded β-CD/CS nanoparticles were 3.6-fold and 1.9-fold higher than that of OVA solution and OVA loaded chitosan nanoparticles, respectively. In vivo evaluation results showed that OVA loaded CD/CS nanoparticles could enhance its efficacy for inducing intestinal mucosal immune response. In conclusion, our data suggested that CD/CS nanoparticles could serve as a promising antigen-delivery system for oral vaccination.

关键词： β-cyclodextrin Chitosan nanoparticles Ovalbumin Oral protein delivery Intestinal mucosal immunity

Exosome-based small RNA delivery:Progress and prospects

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Asian Journal of Pharmaceutical Sciences 2018年第1期13卷 1-11页

作者： Mei Lu Haonan Xing Zhe Xun Tianzhi Yang Pingtian Ding Cuifang Cai Dongkai Wang Xiaoyun Zhao School of Pharmacy Shenyang Pharmaceutical University Institute of Metabolic Disease Research and Drug Development China Medical University Department of Basic Pharmaceutical Sciences School of Pharmacy Husson University School of Life Science and Biopharmaceutics Shenyang Pharmaceutical University

RNA interfering(RNAi), mediated by small interfering RNAs and microRNAs, is currently one of the most promising tools of gene therapy. Small RNAs are capable of inducing specific post-transcriptional gene silencing, providing a potentially effective platform for the treatment of a wide array of diseases. However, similar to other nucleic acid-based drugs,the major hurdle of RNAi therapy is lack of efficient and non-immunogenic delivery vehicles. Currently, viruses, synthetic polymers, and lipid-based carriers are among the most widely studied vehicles for small RNA delivery. However, many drawbacks are reported to be associated with these delivery vehicles. There is a pressing need to replace them with more efficient and better-tolerated approaches. Exosomes secreted from the endocytic compartment of live cells, are a subtype of endogenous extracellular vesicles that transfer genetic and biochemical information among different cells, thus playing an important role in cellcell communication. Recently, accumulating attention has been focused on harnessing exosomes as nanaocarriers for small RNAs delivery. Due to their natural role in shuttling endogenous nucleic acid in our body, exosomes may exhibit higher delivery efficiency, lower immunogenicity, and better compatibility than existing foreign RNA carriers. Importantly,exosomes own intrinsic homing capacity that can guide small RNAs across natural membranous barriers. Moreover, such a capacity can be further improved by adding appropriate targeting moieties. In this manuscript, we briefly review the progress and challenges of RNAi therapy, and discuss the potential of exosomes' applications in small RNA delivery with focus on the most recent advances in exosome-based small RNA delivery for disease therapy.

关键词： Exosomes RNA interfering Small RNAs delivery Neurological disorders Tumors

Silk Fibroin Microspheres: Preparation and Application for Controlled Drug delivery

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Journal of Donghua University(English Edition) 2014年第5期31卷 675-680页

作者：王群张克勤 National Engineering Laboratory for Modern Silk College of Textile and Clothing EngineeringSoochow University

Silk fibroin( SF),a natural protein polymer,has several unique properties such as aqueous processability,biocompatibility,and *** to these advantageous properties,it is promising for applications in various fields,especially drug *** this paper, the simple preparation of SF microspheres was discussed via *** of SF's physicochemical properties and morphology were also *** results show that the morphology,size and size distribution of silk microspheres depend upon various processing parameters, especially including volume ratios among SF,ethanol and polyvinyl alcohol( PVA).Regular silk microspheres were obtained in PVA solution when adjusting the volume ratios of silk to ethanol from 20 ∶ 1 to 20 ∶ *** also found that SF microspheres with various appearances were formed by addition of different PVA solution concentrations under a constant silk solution to ethanol volume *** the Fourier transform infrared spectroscopy( FTIR) of silk microspheres,it was found that introducing ethanol into the SF solution induced conformational change from random coil to β-***, under the observation of scanning electron microscopy( SEM),the shape of self-assembled silk microspheres was determined to be ***,SF's potential as drug delivery carriers was discussed in the experimental results.

关键词： silk microspheres β-sheet drug delivery

ROS-responsive drug delivery systems for biomedical applications

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Asian Journal of Pharmaceutical Sciences 2018年第2期13卷 101-112页

作者： Wenhui Tao Zhonggui He Wuya College of Innovation Shenyang Pharmaceutical University

In the field of biomedicine, stimuli-responsive drug delivery systems(DDSs) have become increasingly popular due to their site-specific release ability in response to a certain physiological stimulus, which may result in both enhanced treatment outcome and reduced side effects. Reactive oxygen species(ROS) are the unavoidable consequence of cell oxidative metabolism. ROS play a crucial part in regulating biological and physiological processes,whereas excessive intracellular ROS usually lead to the oxidation stress which has implications in several typical diseases such as cancer, inflammation and atherosclerosis. Therefore,ROS-responsive DDSs have elicited widespread popularity for their promising applications in a series of biomedical research because the payload is only released in targeted cells or tissues that overproduce ROS. According to the design of ROS-responsive DDSs, the main release mechanisms of therapeutic agents can be ascribed to ROS-induced carrier solubility change, ROS-induced carrier cleavage or ROS-induced prodrug linker cleavage. This review summarized the latest development and novel design of ROS-responsive DDSs and discussed their design concepts and the applications in the biomedical field.

关键词： Drug delivery system Stimuli-responsive Reactive oxygen species ROS-induced solubility change ROS-induced cleavage Applications

Current developments in drug delivery with thermosensitive liposomes

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Asian Journal of Pharmaceutical Sciences 2019年第4期14卷 365-379页

作者： Hongshu Bi Jianxiu Xue Hong Jiang Shan Gao Dongjuan Yang Yan Fang Kai Shi Institute of New Drug Development Liaoning Yaolian Pharmaceutical Co.Ltd.BenxiLiaoning 117004China School of Pharmacy Shenyang Pharmaceutical UniversityBenxiLiaoning 117004China

Thermosensitive liposomes(TSLs) have been an important research area in the field of tumor targeted chemotherapy. Since the first TSLs appeared that using 1,2-dipalmitoyl-snglyce-ro-3-phosphocholine(DPPC) as the primary liposomal lipid, many studies have been done using this type of liposome from basic and practical aspects. While TSLs composed of DPPC enhance the cargo release near the phase transition temperature, it has been shown that many factors affect their temperature sensitivity. Thus numerous attempts have been undertaken to develop new TSLs for improving their thermal response performance. The main objective of this review is to introduce the development and recent update of innovative TSLs formulations, including combination of radiofrequency ablation(RFA), highintensity focused ultrasound(HIFU), magnetic resonance imaging(MRI) and alternating magnetic field(AMF). In addition, various factors affecting the design of TSLs, such as lipid composition, surfactant, size and serum components are also discussed.

关键词： Thermosensitive liposomes Content release rate Hyperthermia Tumor chemotherapy Smart liposomes Drug delivery

Redox-responsive biocompatible nanocarriers based on novel heparosan polysaccharides for intracellular anticancer drug delivery

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Asian Journal of Pharmaceutical Sciences 2020年第1期15卷 83-94页

作者： Lipeng Qiu Lu Ge Miaomiao Long Jing Mao Kamel SAhmed Xiaotian Shan Huijie Zhang Li Qin Guozhong Lv Jinghua Chen School of Pharmaceutical Sciences Jiangnan UniversityWuxi 214122China Wuxi Higher Health Vocational Technology School Wuxi 214028China Wuxi Third Renmin Hospital Wuxi 214041China

Heparosan is a natural precursor of heparin biosynthesis in mammals. It is stable in blood circulation but can be degraded in lysosomes, showing good biocompatibility and long circulation features. So heparosan can be designed as anticancer drug carriers to increase tumor selectivity and improve the therapeutic effect. A novel redox-sensitive heparosancystamine-vitamin E succinate(KSV) micelle system was constructed for intracellular delivery of doxorubicin(DOX). Simultaneously, the redox-insensitive heparosan-adipic acid dihydrazide-vitamin E succinate copolymer(KV) was synthesized as control. DOX-loaded micelles(DOX/KSV) with an average particle size of 90–120 nm had good serum stability and redox-triggered depolymerization. In vitro drug release test showed that DOX/KSV micelles presented obvious redox-triggered release behavior compared with DOX/KV. Cytotoxicity and cell uptake were investigated using MGC80-3 tumor cells and COS7 fibroblast-like cells. The cell survival rate of blank micelles was more than 90%, and the cytotoxicity of DOX/KSV in MGC80-3 cells was higher than in COS7 cells, indicating that the carrier has better biocompatibility and less toxicity side effect. The cytotoxicity of DOX/KSV against MGC80-3 cells was significantly greater than that of free DOX and DOX/KV. Furthermore, compared with DOX/KV in MGC80-3 cells, DOX/KSV micelles uptook more anticancer drugs and then released DOX faster into the cell nucleus. The micelles were endocytosed by multiple pathways, but clathrin-mediated endocytosis was the main pathway. Therefore, heparosan polysaccharide could be a potential option as anticancer carrier for enhancing efficacy and mitigating toxicity.

关键词： Heparosan Vitamin E succinate Redox-sensitive micelles Drug delivery