Current approaches to stabilising and analysing proteins during microencapsulation in PLGA

van der Walle, Christopher F. and Sharma, Gaurav and Kumar, M.N.V Ravi (2009) Current approaches to stabilising and analysing proteins during microencapsulation in PLGA. Expert Opinion on Drug Delivery, 6 (2). pp. 177-186. ISSN 1742-5247 (http://dx.doi.org/10.1517/17425240802680169)

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Abstract

Encapsulation of biomacromolecules in polyester micro- and nano-particles is now a routine procedure in many laboratories for achieving controlled and targeted delivery strategies. Objectives: 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 stabilisers and/or excipients. A number of spectroscopic and spectrometric methods have found new application to the study of protein integrity in microspheres.

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