In vitro and in vivo release of albumin from an electrostatically crosslinked in situ-forming gel

Abstract

Delivery systems capable of maintaining a sustained release of protein drugs at specific sites can potentially circumvent problems of toxicity and subtherapeutic local dosing levels associated with systemic administration. Here, we used bovine serum albumin (BSA) as a test protein to explore the potential utility of an in situ-forming gel consisting of sodium carboxymethylcellulose (CMC) and polyethyleneimine (PEI) as a depot for protein drugs. BSA-FITC-loaded CMC/PEI solutions were easily prepared and remained liquid at room temperature. When these solutions were subcutaneously injected into rats, they immediately gelled, forming an electrostatically crosslinked three-dimensional network structure that showed sustained release of BSA-FITC for 15 days in vitro and in vivo. No BSA-FITC remained in CMC/PEI gels after this time, indicating complete release of protein cargo. The sustained release of BSA-FITC was also monitored by real-time molecular imaging, which showed that BSA-FITC bioavailability in BSA-FITC-loaded CMC/PEI gels was more than twice that of BSA-FITC-only solutions. CMC/PEI gels provoked only a modest inflammatory response. Collectively, our results show that the CMC/PEI gel described here could serve as a minimally invasive therapeutics depot with numerous benefits compared to orally or intravenously administered drugs.