Fuente: Journal of applied polymer Lugar: RESEARCH ARTICLE An amphiphilic mPEG-P4HB copolymer was developed using IPDI coupling and formulated into 80 nm nanoparticles via the nanoprecipitation method. The system achieved a high curcumin loading of 64.6%, significantly enhancing its aqueous solubility and alkali stability, which led to superior cellular uptake and cytotoxicity. These results position mPEG-P4HB as a promising carrier for hydrophobic therapeutics.

ABSTRACT
Polyhydroxyalkanoate (PHA) is a promising class of aliphatic biopolyester due to its biocompatibility and biodegradable nature. As the only PHA-based material approved by the Food and Drug Administration (FDA) for biomedical applications, poly-4-hydroxy-butyrate (P4HB) is especially suitable for medical applications due to its extremely high elasticity and less acidic degradation products. The PEG modification is a widely used strategy in drug delivery to reduce the immunogenicity as well as prolong the blood retention time. Here, we synthesized the amphiphilic copolymer mPEG-P4HB via isophorone diisocyanate (IPDI), which was then formulated into nanoparticles (NPs) by the nanoprecipitation method. Curcumin (Cur)-loaded NPs were used to assess its application as a drug carrier for the hydrophobic anticancer agents. The NPs exhibited a high encapsulation efficiency for Cur (64.6%) and showed a relatively much smaller particle size (80 nm) than most of the reported P4HB-based NPs. It was found that after encapsulating with mPEG-P4HB, the water solubility and alkali stability of Cur were significantly improved. Besides, it showed a sustained Cur release pattern, superior hemocompatibility, more potent cytostatic effect, and enhanced cellular uptake capability than that of free Cur. Overall, mPEG-P4HB-based NPs offer significant potential for the sustained delivery of the hydrophobic antineoplastic drugs.