蛋白多肽类口服给药微粒载体研究进展

蛋白多肽类药物已经成为国内外药学研究和开发的热点,文中介绍几种给药微粒载体在多肽蛋白类药物口服中的应用,分别阐述了纳米粒、微球、脂质体、微乳等的应用和研究新成果。上述新型给药微粒载体研究在蛋白多肽药物制备中取得较大进展,明显改善了蛋白多肽药物的稳定性和体内药动学性质,在蛋白多肽药物研究中有广阔的应用前景。     

口服结肠定位给药系统的研究进展

口服结肠定位给药系统（oral colon—specific drug delivery system，OCDDS）是通过多种制剂技术使药物口服后，在胃及小肠内不释放，只有到达回盲部或结肠部位才定位释放药物的一种新型药物控释系统。利用结肠定位给药系统可将治疗结肠疾病的药物靶向输送至结肠，不仅降低了常规的口服或直肠给药的毒副作用，且能将药物输送至病灶处，可减少给药剂量，提高疗效，从而提高患者的顺应性；同时结肠靶向给药可以避免药物在胃肠道上端被胃肠道酶所降解，提高了多肽、蛋白、疫苗类药物的口服给药的生物利用度。     

蛋白多肽类药物纳米粒口服给药系统的研究进展

目的综述近年来纳米粒作为蛋白质多肽类药物口服传递系统方面的研究现状和进展。方法分析有关文献资料,从纳米粒给药系统的载体材料、口服药效等方面进行了概述。结果纳米粒给药系统可提高蛋白质和多肽类药物的口服吸收效率,提高此类药物的生物利用度。结论纳米粒给药系统在口服传递蛋白质和多肽类药物方面有着广阔的研究和应用前景。     

聚合物胶束用于口服给药的研究进展

聚合物胶束是由两亲性聚合物自发形成的热力学稳定体系,它对难溶性药物具有良好的增溶效果。许多具有良好活性的药物由于溶解性差,其口服给药受到限制。将聚合物胶束作为口服给药的载体可以显著改善药物的溶解性,增加透过生物膜的药量,进而提高药效。此外,聚合物组成和性质具有多样性,利用聚合物的这一特性可以制备出对pH值、温度敏感或者具有黏膜黏附性的胶束。在提高药物溶解度的同时,通过改变药物在胃肠道中的释放过程,进一步提高其生物利用度。本文主要介绍聚合物胶束在口服给药方面的研究进展,分析并总结其作为口服给药载体应用的特点和前景。     

脂质体肺部给药系统的应用

介绍脂质体作为肺部给药载体的优点及其在抗感染药物、抗哮喘药物、抗肿瘤药物、多肽蛋白类药物、基因药物及抗氧剂的应用。     

蛋白和多肽药物的透粘膜吸收

随着蛋白和多肽药物的增多，其非注射给药剂型的研究受到了越来越多的重视，本文综述了国外对鼻腔、口腔、口服、直肠和阴道几种主要透粘膜吸收给药途径的研究。蛋白和多肽药物的透粘膜给药剂型的研究推进了蛋白和多肽药物的临床应用。     

脂质体肺部给药的研究进展

目的：介绍脂质体肺部给药的方式，评价其安全性。方法：查阅国内外有关文献进行综合分析。结果：主要概述近年来国内外有关脂质体作为抗菌药物、平喘药物、抗癌药物、多肽和蛋白类药物以及基因药物的载体，通过肺部给药发挥局部或全身疗效的研究。结论：可有效地减少药物对正常组织的刺激性和毒性，增加药物疗效；在基因工程上的应用为肺部给药开拓了更为广阔的前景。     

制剂新技术和新型给药系统在蛋白多肽药物研究中的应用

蛋白多肽药物已经成为国内外药学研究和开发的热点,文中介绍几种新制剂技术和新型给药系统在多肽蛋白药物中的应用,分别阐述了聚乙二醇(PEG)修饰技术、聚乙烯吡咯烷酮(PVP)修饰技术、超临界流体技术和脂质体、微粒和纳米粒、脉冲给药系统、微组装给药系统、微乳、聚合物胶束等的应用和研究新成果.上述新技术和新给药系统研究在多肽蛋白药物制备中取得较大进展,明显改善了蛋白多肽的稳定性和体内药动学性质,在新蛋白多肽药物研究中有广阔的应用前景.     

口服结肠靶向给药系统研究进展

口服结肠靶向给药系统（oral colon targeting drug delivery system,OCTDDS）是通过药物传输系统,使药物口服后在上消化道不释放,而将药物运送到人体回盲部或结肠后开始崩解或蚀解释放出来,从而使药物在人体大肠发挥局部或全身治疗作用。OCTDDS是上世纪90年代后期发展起来的新型给药方式,它对于溃疡性结肠炎、结肠直肠癌的局部治疗和蛋白多肽类药物口服给药以及哮喘、关节炎的缓释治疗中,提高药物疗效,降低药物引起的全身不良作用具有重要意义。     

脂质立方液晶纳米粒作为药物载体的研究进展

由两亲性脂质分散在水性环境中自发形成各种几何形态构成的药物输送载体正成为制剂载药系统研究的热点之一。脂质立方液晶纳米粒是一定浓度的两亲性脂质分散在水溶液中自组装成含双连续水区和脂质区的闭合脂质双层“蜂窝状(海绵状)”结构,该独特的内部双水道结构和巨大膜表面积使其能够包封各种不同极性和剂量的药物,具有多样化的药物包裹性。作为药物载体,脂质立方液晶纳米粒还具有载药量大、保护多肽蛋白类药物和制备工艺简单等优点;可口服、局部黏膜和注射等多种途径给药,在多种剂型中有广泛的应用。本文对脂质立方液晶纳米给药系统的研究进行归纳和总结,并展望了脂质立方液晶纳米粒新型药物载体的应用前景。     

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.     

The use of multifunctional polymers for non-invasive peptide and protein application

For the efficient delivery of peptide and protein drugs by non-invasive routes various strategies have been pursued to overcome enzymatic and mucosal barriers to gain sufficient bioavailability. Among such delivery systems multifunctional polymers have received considerable attention, which is reflected by numerous publications and patents. They are able to provide a controlled release for therapeutic peptides and proteins being embedded in the polymeric network either based on a simple diffusion process or on the biodegradation of the carrier matrix. Additionally, polymers such as polyacrylates display an inhibitory effect towards various proteases located on the absorption membrane. In combination with enzyme inhibitors, this protective effect towards enzymatic attack may further be improved. Moreover, polyacrylates and chitosan display a permeation enhancing effect, in particular for the paracellular uptake of peptide drugs from mucosal tissues. If these polymers also exhibit mucoadhesive properties, the concentration gradient of the drug on the mucosa can be increased and in the case of oral delivery the presystemic enzymatic degradation of the (poly)peptide drug in the intestine between the delivery system and the absorption membrane can be reduced. Delivery systems utilising multifunctional polymers include formulations such as nano- and microspheres, pellets and matrix-tablets.     

短肽在靶向药物递送系统中的研究进展

近年来研究发现许多肿瘤细胞表面高表达一些肽类受体，这些肽类受体与相应的配体亲和性高，能以配体-受体方式特异性结合。以小片段活性肽作为导向物形成复合物而发展的靶向药物递送系统，能够将药物定向转运到靶细胞内，显示了良好的研究价值和应用前景。如蛙皮素/胃泌素释放肽受体介导的靶向药物递送系统、生长抑素受体介导的靶向药物递送系统、十肽SynB₃受体介导的靶向药物递送系统、黄体酮释放激素受体介导的靶向药物递送系统及其他肽类受体介导的靶向药物递送系统，其中短肽作为靶向基团与阿霉素、吡咯阿霉素、甲氨蝶呤、顺铂和喜树碱等结合形成高效的复合物，用于表达有相应受体的肿瘤，获得靶向治疗的研究非常有意义。     

转铁蛋白及其受体作为药物载体的研究进展

目的介绍转铁蛋白及其受体在药学中的应用和新的研究方向。方法通过查阅近年来国内外有关转铁蛋白和转铁蛋白受体特点及其应用的文献,综述了转铁蛋白和转铁蛋白受体的特点和分类;转铁蛋白转运金属离子的能力;利用转铁蛋白受体的抗体向脑部转运药物的应用;转铁蛋白和转铁蛋白受体的抗体与药物的结合方法及应用。结果转铁蛋白具有多态性,主要被划分为血清转铁蛋白、卵(清)转铁蛋白和乳(清)转铁蛋白;转铁蛋白受体主要有转铁蛋白受体1和转铁蛋白受体2;转铁蛋白既能转运金属离子又能转运化学药物及基因药物,并在利用转铁蛋白受体的抗体向脑部转运药物方面显示出巨大的应用前景;转铁蛋白可与药物通过静电引力直接吸附,也可以与药物通过共价键结合。结论转铁蛋白及转铁蛋白受体在靶向药物转运中得到了有效的应用,并将受到更为广泛的关注。     

离子交换树脂在药剂学中的应用进展

离子交换树脂药物载体在给药系统中的应用由于具有很多优点而得到了人们的重视。目前在控释、透皮给药、定位给药、速溶、离子导入透皮、鼻腔、局部给药和掩盖药物苦味等方面都有很深入的研究，在缓控释给药中占有特殊的地位。综述了这一药物载体在给药系统和作用部位应用的新进展，并对其应用前景进行了展望。     

Transport of Human Recombinant Brain-Derived Neurotrophic Factor (BDNF) Through the Rat Blood−Brain Barrier in Vivo Using Vector-Mediated Peptide Drug Delivery

The blood–brain barrier (BBB) transport of brain-derived neurotrophic factor (BDNF) in anesthetized rats was examined in the present studies using vector-mediated peptide drug delivery. Following tritiation, the BDNF was biotinylated via a disulfide linker and was coupled to a covalent conjugate of neutral avidin (NLA), which binds the biotinylated peptide with a high affinity, and the murine OX26 monoclonal antibody to the rat transferrin receptor. Owing to the abundance of transferrin receptors on brain capillary endothelium, the OX26 monoclonal antibody undergoes receptor-mediated transcytosis through the BBB, and the NLA–OX26 conjugate transports biotinylated peptide therapeutics through the BBB. The present studies show that while unconjugated BDNF was not transported through the BBB in vivo, the conjugation of biotinylated BDNF to the NLA–OX26 vector resulted in a marked increase in the brain delivery of BDNF, as defined by measurements of the percentage of the injected dose (ID) delivered per gram of brain. Although BDNF was not transported through the BBB in vivo, this cationic peptide was avidly bound by isolated human brain capillaries via a low-affinity, high-capacity system that was inhibited by protamine and by serum protein binding of BDNF. In conclusion, these studies show that the delivery of unconjugated BDNF to brain is nil owing to the combined effects of negligible BBB transport and rapid systemic clearance of intravenous administered BDNF. The brain delivery of BDNF may be augmented by conjugation of BDNF to BBB drug delivery vectors, such as the NLA–OX26 conjugate.     

Mechanisms of TfR-mediated transcytosis and sorting in epithelial cells and applications toward drug delivery

Transferrin receptor has been an important protein for many of the advances made in understanding the intricacies of the intramolecular sorting pathways of endocytosed molecules. The unique internalization and recycling functions of transferrin receptor have also made it an attractive choice for drug targeting and delivery of large protein-based therapeutics and toxins. Recent advances in elucidating the role of the intracellular controllers of transferrin recycling and sorting, such as Rab proteins and their effectors, have led to enhancement of transferrin receptor as a drug delivery vehicle. This review focuses on the use of transferrin receptor as an agent for facilitating drug delivery and targeting, and the role that mechanisms of transferrin receptor sorting and transcytosis play in these events.     

Ceramic nanocarriers: versatile nanosystem for protein and peptide delivery

Introduction: Proteins and peptides have been established to be the potential drug candidate for various human diseases. But, delivery of these therapeutic protein and peptides is still a challenge due to their several unfavorable properties. Nanotechnology is expanding as a promising tool for the efficient delivery of proteins and peptides. Among numerous nano-based carriers, ceramic nanoparticles have proven themselves as a unique carrier for protein and peptide delivery as they provide a more stable, bioavailable, readily manufacturable, and acceptable proteins and polypeptide formulation.

Areas covered: This article provides an overview of the various aspects of ceramic nanoparticles including their classification, methods of preparation, latest advances, and applications as protein and peptide delivery carriers.

Expert opinion: Ceramic nanocarriers seem to have potential for preserving structural integrity of proteins and peptides, thereby promoting a better therapeutic effect. This approach thus provides pharmaceutical scientists with a new hope for the delivery of proteins and peptides. Still, considerable study on ceramic nanocarrier is necessary with respect to pharmacokinetics, toxicology, and animal studies to confirm their efficiency as well as safety and to establish their clinical usefulness and scale-up to industrial level.     

自组装短肽原位凝胶用作蛋白药物载体的初步研究

目的:研究自组装短肽原位凝胶用作蛋白药物载体的可能性。方法:以自组装短肽RAD16-Ⅰ为代表,以溶菌酶为模型蛋白,通过流变学试验表征含蛋白的自组装短肽溶液原位成水凝胶特性,并通过体外试验初步研究蛋白的释放特性。结果:含蛋白的自组装短肽溶液在接触到磷酸盐缓冲溶液后能够迅速形成水凝胶;蛋白容易从中释放并表现出一定的控释作用,8h累积释药量均大于80%,1.5%的RAD16-Ⅰ载蛋白水凝胶24h蛋白累积释药量小于90%;蛋白的结构完整性和活性得到了很好的保持,释放样品中溶菌酶相对活性为98%～115%。结论:自组装短肽具有作为蛋白类药物原位水凝胶载体的潜力。     

Recent developments in superporous hydrogels

Superporous hydrogels (SPHs) were originally developed as a novel drug delivery system to retain drugs in the gastric medium. These systems should instantly swell in the stomach and maintain their integrity in the harsh stomach environment, while releasing the pharmaceutical active ingredient. For years, the synthetic features and properties of these SPH materials have been modified and improved to meet the requirements for gastric retention applications. Furthermore, an instant swelling hydrogel has also shown potential application for peroral intestinal peptide and protein absorption. This review discusses the formulation, characterization, properties and applications of these polymers.