多囊脂质体研究进展

Research process of multivesicular liposomes

自1983年以来,作为脂质体家族的一员,多囊脂质体(MVLs)在生物材料和医学领域逐渐引起人们的关注。多囊脂质体由于其蜂窝状的内部结构,克服了传统脂质体在亲水性药物包埋率和稳定性方面的缺点。由于MVLs内水相体积大,药物包埋率高,具有很好的缓释效果。目前文献报道的多囊脂质体的尺寸大多在10μm以上,主要在镇痛药包埋方面取得了良好的进展。本工作综述了近年来MVLs的制备方法、表征设备、释药机制,归纳了临床研究现状、商品化产品和应用研究进展,同时还提出了MVLs在小尺寸、多样化生物医学应用和放大策略方面的挑战及未来前景。

Since 1983,multivesicular liposomes(MVLs),as a member of the liposome family,have been of interest in the biomaterials and medical fields.MVLs have multiple aqueous compartments separated by phospholipid bilayers and an internal aqueous phase of up to 90%.They also have the advantages of reducing the number of injections,extending the duration of drug action,and improving patient compliance.So far,most of the MVLs reported in the literature are above 10μm in size and have made good progress mainly in the encapsulation of analgesic drugs.This review provides an overview of the preparation methods,characterization methods,and drug release mechanisms of MVLs that have been reported in the literature in the last decade.There are relatively several methods for preparing MVLs,including the double emulsification method,spray atomization technique,and electroforming method.Currently,the main characterization methods used for MVLs are optical/fluorescent confocal imaging,scanning electron microscopy imaging,determination of particle size distribution,entrapment efficiency,and determination of zeta potential.Because of the large volume of the internal aqueous phase of MVLs and the high hydrophilic drug encapsulation rate of the internal vesicles,the individual vesicles gradually rupture and the hydrophilic drug gradually gets released during in vitro release,with a three-phase release pattern of sustained release.This review also summarizes the current status of clinical studies and types of commercialized products.At present,the application of MVLs regarding analgesics has reached stagesⅡ-Ⅳ,and three commercialized formulations have entered the clinic with satisfactory results.Moreover,this review summarizes the current progress in applied research,mainly in the delivery of anticancer drugs,analgesic drugs,and protein peptides.Last but not least,the challenge and prospects regarding small-sized MVLs,diverse biomedical applications,and scale-up strategies are proposed.