van der Walle Christopher F, Sharma Gaurav, Ravi Kumar Mnv
University of Strathclyde, Strathclyde Institute of Pharmacy and Biomedical Sciences, 27 Taylor Street, Glasgow G40NR, UK.
Expert Opin Drug Deliv. 2009 Feb;6(2):177-86. doi: 10.1517/17425240802680169.
Encapsulation of biomacromolecules in polyester micro- and nano-particles is now a routine procedure in many laboratories for achieving controlled and targeted delivery strategies.
Proteins are notoriously difficult to encapsulate without some degree of unfolding and loss of bioactivity, and this is despite around two decades of research. A case by case analysis appears necessary when determining which mechanism, generally unfolding at the emulsion interface or acidification of the particle interior, is most detrimental. The transient nature of the emulsion systems makes in situ, real-time analysis of interfacial events difficult, necessitating interpretation from model interfacial systems or analysis post-fabrication.
The review will focus on: i) the emulsification efficiency of proteins, cf. interfacial adsorption; ii) current excipients and techniques used to stabilise proteins, outlining work towards the oral delivery of insulin as a case study; iii) analytical techniques used to characterise encapsulated protein.
There appears to be a recent trend towards the stabilization of proteins via direct complexation with polymers but, in contrast, emulsion techniques are emerging which err away from the use of stabilizers and/or excipients. A number of spectroscopic and spectrometric methods have found new application to the study of protein integrity in microspheres.
在许多实验室中，将生物大分子包裹于聚酯微米和纳米颗粒内现已成为实现可控靶向递送策略的常规方法。
众所周知，蛋白质在包裹过程中极易发生一定程度的解折叠并丧失生物活性，尽管已有约二十年的研究，但情况依然如此。在确定哪种机制（通常是在乳液界面处解折叠或颗粒内部酸化）最为有害时，似乎有必要进行逐案分析。乳液体系的瞬态性质使得对界面事件进行原位实时分析变得困难，这就需要从模型界面体系进行解读或在制备后进行分析。
本综述将聚焦于：i）蛋白质的乳化效率，对比界面吸附；ii）当前用于稳定蛋白质的辅料和技术，以胰岛素口服递送的研究为例进行概述；iii）用于表征包裹蛋白质的分析技术。
近期似乎出现了一种通过与聚合物直接络合来稳定蛋白质的趋势，但相比之下，也出现了一些不使用稳定剂和/或辅料的乳液技术。许多光谱和光谱测定方法已在微球中蛋白质完整性研究中得到新应用。
