Structure‐guided Encapsulation of Bovine Serum Albumin in Poly(DL‐lactic‐co‐glycolic) Acid

Abstract

Protein stability is a limiting factor when encapsulating proteins in polymeric matrices for sustained release. We present an approach to stabilize protein structure upon encapsulation in hydrophobic, synthetic polymers. Bovine serum albumin (BSA) was encapsulated in the biocompatible polymer poly(DL-lactic-co-glycolic) acid (PLGA) using a non-aqueous approach. Fourier-transform infrared (FTIR) spectroscopy was used as a non-invasive structural probe to guide the optimization of the encapsulation process. The secondary structure of BSA was determined under relevant conditions from the amide I region after resolution enhancement by Gaussian curve-fitting. The α-helix content was used to describe the structural integrity of BSA. BSA was co-lyophilized with twelve different polyol lyoprotectants to identify efficient excipients for structural preservation upon freeze-drying. Sorbitol, glucose, trehalose and lactitol largely prevented lyophilization-induced structural alterations in BSA. However, only formulations with trehalose allowed the formation of a homogeneous fine suspension in the organic solvent methylene chloride, and were therefore used in the encapsulation procedure. This fine suspension is essential in drug-delivery devices to avoid burst release. Exposure of the BSA-trehalose co-lyophilizate to conditions relevant to the encapsulation process did not result in any further structural alterations. The encapsulation process was guided using FTIR spectroscopy as a non-invasive probe and, by selecting the appropriate conditions, we were able to preserve protein secondary structure in all the steps before and during the encapsulation in PLGA.