Protein–Polymer Coassembly Supraparticles as a Polyester-Based Drug Delivery Carrier with Ultrahigh Colloidal Stability and Drug Loading

Poly(esters), especially poly(lactic-<i>co</i>-glycolic acid) (PLGA), are currently the materials of choice for clinical sustained-drug-release formulations based on polymer nanoparticles, due to the long history of safe clinical use of these polymers. The existing poly(ester) nanoparticles suffer from limitations in low colloidal stability or/and low drug loading. Here, we present a poly(ester)-based nanoparticle with ultrahigh colloidal stability (>210 days) and ultrahigh drug loading (∼40% for doxorubicin, or DOX). This drug delivery nanoparticle is formed by spontaneous coassembly between a protein (BSA as a model here) and a hydrophobic polymer (PLGA as a model here), yielding a protein-polymer coassembly supraparticle (PPCAS). We further investigate two different methods to load DOX into PPCAS, namely, coassembly (with hydrophobic interaction as the primary driving force) and solvent diffusion (with concentration gradient as the primary driving force). We find that combining the two loading methods can yield higher drug loading than using one method alone, supporting the complementary nature of the two loading methods. We show the sustained drug release behavior of PPCAS and explore its application in anticancer therapy. Finally, in preliminary studies of scale-up production, we demonstrate that the production of PPCAS and drug-loaded PPCAS can be scaled up without significant loss of product quality.