微粒作为靶向制剂载体的研究进展

综述了脂质体、微球、毫微粒、乳剂、红细胞５种包蔽型微粒载体系统和合成大分子、生物大分子、抗体３种化学交联型微粒载体系统的研究进展。微粒作为靶向制剂载体的研究已经取得了重大成绩，并仍在迅速发展中     

凝集素修饰透黏膜微粒给药系统

通过对近年来相关文献的检索,本文介绍了凝集素修饰的微球、纳米粒和脂质体,以及凝集素对不同微粒系统的修饰机制,综述凝集素修饰微粒给药系统在透黏膜给药中的应用,认为凝集素修饰微粒给药系统有较好的应用前景。     

注射用乳剂作为给药载体

一、引言应用药物载体作为增进药物疗效的一种方法目前已被人们广泛认识。已经注意到几种不同类型的个别载体,诸如可生物降解的多聚物、可溶性的大分子和其它已经应用的给药系统。微粒型载体包括所有胶体系统,如脂质体、乳剂、微囊、微粒和毫微粒无疑将用于注射给药。微粒载体对抗真菌药和免疫调节剂特别有用,因为它们在体内是被动地集中在巨噬细胞簇里。脂质体是广泛研究过     

喷雾冷冻干燥技术制备盐酸伊立替康脂质体冻干微粒及其理化性质考察

目的:考察喷雾冷冻干燥(SFD)技术制备脂质体冻干微粒的可行性。方法:以盐酸伊立替康为模型药物,采用硫酸铵梯度法制备盐酸伊立替康脂质体,SFD技术制备脂质体冻干微粒;以喷嘴高度、物料流速、雾滴/液氮质量比为因素,应用Box-Behnk-enDesign(BBD)试验考察三者之间的配比对微粒包封率的影响以优化SFD工艺,并对所制备的脂质体及冻干微粒的理化性质进行了考察。结果:SFD优化工艺为物料流速5.5mL·min-1,喷嘴高度18.5cm,雾滴/液氮质量比3.7%,由此制备的脂质体冻干微粒的外观和再分散性好,平均粒径、粒度分布、主药含量及包封率等理化性质与原脂质体基本保持一致,且放置6个月后与原脂质体溶液比较稳定性更好。结论:SFD技术制备脂质体冻干微粒具有可行性,并提高了脂质体的稳定性。     

药物载体系统的研究进展

综述了药物载体系统在近些年的新发展，特别是对脂质体，脂微粒和毫微粒3种载体系统的制剂和药效学等方面研究进行了论述，为研究开发载体制剂提供参考。     

固体脂质纳米粒技术及其应用

固体脂质纳米粒(solid lipid nanoparticles,SLN)是20世纪90年代初发展起来的继乳剂、脂质体、微粒和毫微粒后,新一代的性能优越的亚微粒给药系统,是指粒径在10～1000nm的胶体给药系统,以毒性低、生物相容性好、生物可降解的固态天     

靶向载药系统毫微粒及其应用

近年来发展了一系列新的载药系统如脂质体和纳米级大小的固态颗粒系统。后者被称作毫微粒(nanoparticles)。毫微粒用于运载药物,可以降低循环系统中游离药物或蛋白结合药物的量;减少用药量;可以使药物在某些     

肝靶向微粒给药系统的研究进展

目的对近年来微粒给药系统在肝靶向治疗的研究进展做一综述。方法根据国内外文献资料进行整理归纳。结果纳米粒、微球、脂质体及微乳等微粒系统具有被动靶向于肝的趋势,利用肝细胞表面某些受体则可特异性靶向于肝达到主动靶向作用。结论微粒给药系统在肝靶向治疗领域具有重要意义。     

肝靶向微粒给药系统的研究进展

目的对近年来微粒给药系统在肝靶向治疗的研究进展做一综述。方法根据国内外文献资料进行整理归纳。结果纳米粒、微球、脂质体及微乳等微粒系统具有被动靶向于肝的趋势,利用肝细胞表面某些受体则可特异性靶向于肝达到主动靶向作用。结论微粒给药系统在肝靶向治疗领域具有重要意义。     

药物制剂研究展望

本文就药物制剂的研究情况及发展趋向作了论述，并介绍了较前沿的一些制剂研究领域，如肽和蛋白质类药物给药系统、毫微粒制剂、前体脂质体、离子电渗透皮给药和自控释药系统等。     

Biodistribution of Cyclosporin Encapsulated in Liposomes Modified with Bioadhesive Polymer

The purpose of this investigation was to study the possibility of renewing the immunosuppressive activity of cyclosporin by formulating the compound in liposomes modified with bioadhesive polymers. The liposomes prepared were evaluated both pharmacokinetically and pharmacodynamically. Tissue distribution and plasma pharmacokinetics of cyclosporin and model dye, sudan black, which is as hydrophobic as cyclosporin, were studied in rats after intravenous infusion (10 mg kg^?). The immunosuppressive efficacy of liposomal cyclosporin preparations was studied in the allogenic rat-heart-transplantation model, where cyclosporin therapy (10 mg kg^?) continued for one week. The entrapment of sudan black in liposomes modified with bioadhesive polymers resulted in higher sudan black delivery to the spleen and the liver than with standard sudan-black-loaded liposomes. Among the modified liposomes, those modified with carbopol 941 showed the most remarkable enhancing effect on the delivery of sudan black to these organs and total plasma clearance of sudan black decreased to 38.6 ± 7.8 mL h^? kg^? (standard liposomes, 58.9 ± 64 mL h^? kg^?). Delivery of cyclosporin to the spleen and the liver was increased approximately twofold by modifying the liposomes with carbopol 941. In the preliminary study on the allogenic rat-heart-transplantation model, the mean survival days of the graft were 18.8 ± 2.9 days for the group receiving cyclosporin liposomes modified with carbopol 941, 14.2 ± 4.4 days for the group receiving standard cyclosporin liposomes and 7.6 ± 0.5 days for the group receiving cyclosporin solution. The encapsulation of cyclosporin in liposomes modified with bioadhesive polymer enhanced the residence time of cyclosporin in the systemic circulation, resulting in approximately twofold greater delivery of cyclosporin to the spleen and liver. However, in the allogenic rat-heart-transplantation model no significant difference was detected between the immunosuppressive efficacy of cyclosporin encapsulated in bioadhesive polymer-modified liposomes and that encapsulated in standard liposomes.     

Development and characterization of polymer-coated liposomes for vaginal delivery of sildenafil citrate

Vaginal administration of sildenafil citrate has shown recently to develop efficiently the uterine lining with subsequent successful embryo implantation following in vitro fertilization. The aim of the present study was to develop sildenafil-loaded liposomes coated with bioadhesive polymers for enhanced vaginal retention and improved drug permeation. Three liposomal formulae were prepared by thin-film method using different phospholipid:cholesterol ratios. The optimal liposomal formulation was coated with bioadhesive polymers (chitosan and HPMC). A marked increase in liposomal size and zeta potential was observed for all coated liposomal formulations. HPMC-coated liposomes showed the greater bioadhesion and higher entrapment efficiency than chitosan-coated formulae. The in vitro release studies showed prolonged release of sildenafil from coated liposomes as compared to uncoated liposomes and sildenafil solution. Ex vivo permeation study revealed the enhanced permeation of coated relative to uncoated liposomes. Chitosan-coated formula demonstrated highest drug permeation and was thus selected for further investigations. Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) confirmed the successful coating of the liposomes by chitosan. Histopathological in vivo testing proved the efficacy of chitosan-coated liposomes to improve blood flow to the vaginal endometrium and to increase endometrial thickness. Chitosan-coated liposomes can be considered as potential novel drug delivery system intended for the vaginal administration of sildenafil, which would prolong system's retention at the vaginal site and enhance the permeation of sildenafil to uterine blood circulation.     

Characterisation and in vitro evaluation of bioadhesive liposome gels for local therapy of vaginitis

The purpose of this study was to design and evaluate a new vaginal delivery system for the local treatment of vaginitis. Liposomes containing two commonly applied drugs in the treatment of vaginal infections, namely clotrimazole and metronidazole, were prepared by the proliposome and the polyol dilution methods. Both types of liposomes were characterised and compared for particle size, polydispersity, entrapment efficiency, and tested for in vitro stability in media that mimic human vaginal conditions (buffer, pH 4.5, and vaginal fluid simulant). To achieve application viscosity and to further improve their stability, liposomes containing drugs were incorporated in a bioadhesive gel made of Carbopol 974P NF resin. In vitro release studies have demonstrated that even after 24 h of incubation in vaginal fluid simulant (at 37 degrees C) more than 30% of the originally entrapped clotrimazole (or 50% of metronidazole) was still retained in the gel. Storage stability studies have proved the ability of Carbopol 974P NF gel to preserve original size distributions of incorporated liposomes. All the performed experiments confirm the applicability of bioadhesive liposome gels as a novel delivery system for local therapy of vaginal infections.     

Nasal route and drug delivery systems

Nasal drug administration has been used as an alternative route for the systemic availability of drugs restricted to intravenous administration. This is due to the large surface area, porous endothelial membrane, high total blood flow, the avoidance of first-pass metabolism, and ready accessibility. The nasal administration of drugs, including numerous compound, peptide and protein drugs, for systemic medication has been widely investigated in recent years. Drugs are cleared rapidly from the nasal cavity after intranasal administration, resulting in rapid systemic drug absorption. Several approaches are here discussed for increasing the residence time of drug formulations in the nasal cavity, resulting in improved nasal drug absorption. The article highlights the importance and advantages of the drug delivery systems applied via the nasal route, which have bioadhesive properties. Bioadhesive, or more appropriately, mucoadhesive systems have been prepared for both oral and peroral administration in the past. The nasal mucosa presents an ideal site for bioadhesive drug delivery systems. In this review we discuss the effects of microspheres and other bioadhesive drug delivery systems on nasal drug absorption. Drug delivery systems, such as microspheres, liposomes and gels have been demonstrated to have good bioadhesive characteristics and that swell easily when in contact with the nasal mucosa. These drug delivery systems have the ability to control the rate of drug clearance from the nasal cavity as well as protect the drug from enzymatic degradation in nasal secretions. The mechanisms and effectiveness of these drug delivery systems are described in order to guide the development of specific and effective therapies for the future development of peptide preparations and other drugs that otherwise should be administered parenterally. As a consequence, bioavailability and residence time of the drugs that are administered via the nasal route can be increased by bioadhesive drug delivery systems. Although the majority of this work involving the use of microspheres, liposomes and gels is limited to the delivery of macromolecules (e.g., insulin and growth hormone), the general principles involved could be applied to other drug candidates. It must be emphasized that many drugs can be absorbed well if the contact time between formulation and the nasal mucosa is optimized.     

Liposomal gels for vaginal drug delivery

The aim of our study was to develop a liposomal drug carrier system, able to provide sustained and controlled release of appropriate drug for local vaginal therapy. To optimise the preparation of liposomes with regards to size and entrapment efficiency, liposomes containing calcein were prepared by five different methods. Two optimal liposomal preparations (proliposomes and polyol dilution liposomes) were tested for their in vitro stability in media that simulate human vaginal conditions (buffer, pH 4.5). To be closer to in vivo application of liposomes and to achieve further improvement of their stability, liposomes were incorporated in vehicles suitable for vaginal self-administration. Gels of polyacrylate were chosen as vehicles for liposomal preparations. Due to their hydrophilic nature and bioadhesive properties, it was possible to achieve an adequate pH value corresponding to physiological conditions as well as desirable viscosity. In vitro release studies of liposomes incorporated in these gels (Carbopol 974P NF or Carbopol 980 NF) confirmed their applicability as a novel drug carrier system in vaginal delivery. Regardless of the gel used, even 24 h after the incubation of liposomal gel in the buffer pH 4.5 more than 80% of the originally entrapped substance was still retained.     

Liposomal gel with chloramphenicol: characterisation and in vitro release

The aim of our study was to develop a liposomal carrier system for the local treatment of bacterial vaginosis, capable to efficiently deliver entrapped drug during an extended period of time. Chloramphenicol was entrapped in liposomes composed of egg phosphatidylcholine/egg phosphatidylgycerol-sodium (9:1, molar ratio) and prepared by two different methods, the proliposome method and the polyol dilution method. Both liposome preparations were characterised and compared for particle size, polydispersity, entrapment efficiency and tested for in vitro stability in media that simulate human vaginal conditions (buffer pH 4.5 and vaginal fluid simulant). To achieve application viscosity of liposomes and to further improve their stability, liposomes prepared by the proliposome method were incorporated in the bioadhesive gel made of Carbopol 974P NF resin. In vitro release studies of liposomes incorporated in the gel have shown a prolonged release of entrapped chloramphenicol compared to control gel. Even after 24 hours of incubation in the vaginal fluid simulant, more than 40% of the originally entrapped drug was still retained in the gel. Storage stability studies have proven the ability of the Carbopol 974P NF gel to preserve the original size distribution of incorporated liposomes. All the performed experiments confirm the applicability of liposomes as a novel drug carrier system for the local treatment of bacterial vaginosis.     

Cyclodextrin-Mediated Drug Release from Liposomes Dispersed Within a Bioadhesive Gel

Purpose The aim of the present study was to design a new mucosal drug delivery system composed of liposomes dispersed within a bioadhesive hydrogel containing methyl--cyclodextrin (MeCD) for controlled drug release.Methods A hydrophilic model molecule, inulin, was encapsulated within positively charged and PEG-ylated liposomes and its release was measured in the presence of MeCD after vesicle dispersion within the bioadhesive Carbopol® 974P gel. Freeze-fracture electron microscopy (FFEM) was used to follow liposome morphological changes when dispersed within the hydrogel. Liposome-MeCD interactions were investigated by turbidity monitoring during continuous addition of MeCD to liposomes and by FFEM.Results Inulin diffusion within the gel was influenced by Carbopol® 974P concentration since no gel erosion occurred. When dispersed within the gel, positively charged liposomes displayed a higher stability than PEG-ylated vesicles. In the presence of MeCD, higher amounts of free inulin were released from liposomes, especially in Carbopol®-free system. MeCD appeared to diffuse towards lipid vesicles and permeabilized their bilayer allowing inulin leakage. Indeed, freeze-fracture experiments and liposome turbidity monitoring have shown that MeCD behaved as a detergent behavior, resulting in lipid vesicle solubilization.Conclusion MeCD is able to mediate, within a bioadhesive hydrogel, the release of a liposome-encapsulated molecule allowing further application of this delivery system for mucosal administration.Equal Contribution.     

Site-specific drug delivery systems. III. Nasal drug delivery

The nasal cavity has a large surface and a rich blood supplied mucosa. Drugs absorbed by blood vessels pass directly into the systemic circulation, thereby avoiding first-pass metabolism. Numbers of factors limit the intranasal absorption of drugs, especially peptide and protein drugs. These factors are the epithelial and mucus barrier, the rapid mucociliar clearance and the enzymatic activity. Increasing the residence time of the drug formulation in the nasal cavity and a period of contact with nasal mucosa, may improve drug absorption. Approaches to increase the residence time of drug formulations in the nasal cavity usually involve the use of microspheres, liposomes and bioadhesive gels.     

Transport of peptide and protein drugs across biological membranes

The transport characteristics of peptide and proteins drugs across various epithelial membrane barriers are outlines. These include transport through the intestinal, buccal, nasal and pulmonary absorptive mucosae, as well as transdermal penetration. Because peptides and proteins are hydrophilic and high molecular weight compounds, they commonly show minor permeability across the mentioned biological membranes. In order to improve their transport properties and thereby their systemic bioavailability, several strategies can be undertaken, such as the synthesis of stabilized and lipophilic analogues, the application of absorption enhancers and protease inhibitors, and the design of suitable dosage forms (e.g., liposomes, biodegradable nanocapsules, bioadhesive microspheres).     

Auto-associative amphiphilic polysaccharides as drug delivery systems

Self-assembly of amphiphilic polysaccharides provides a positive outlook for drug delivery systems without the need for solvents or surfactants. Various polymeric amphiphilic polysaccharides undergo intramolecular or intermolecular associations in water. This type of association, promoted by hydrophobic segments, led to the formation of various drug delivery systems such as micelles, nanoparticles, liposomes and hydrogels. Here, we review a selection of the most important amphiphilic polysaccharides used as drug delivery systems and their pharmaceutical applications. Attention focuses on amphiphilic chitosan owing to its unique properties such as excellent biocompatibility, non-toxicity and antimicrobial and bioadhesive properties.