Current approaches to stabilising and analysing proteins during microencapsulation in PLGA.
BACKGROUND
Encapsulation of biomacromolecules in polyester micro- and nano-particles is now a routine procedure in many laboratories for achieving controlled and targeted delivery strategies.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.
van der Walle
Christopher F
CF
University of Strathclyde, Strathclyde Institute of Pharmacy and Biomedical Sciences, 27 Taylor Street, Glasgow G40NR, UK. chris.walle@strath.ac.uk
Sharma
Gaurav
G
Ravi Kumar
Mnv
M
D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding; D004655:Emulsions / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D055550:Protein Stability; D011506:Proteins / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry*; D013057:Spectrum Analysis
D004655:Emulsions; D005079:Excipients; D007328:Insulin; D011506:Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid