Biodegradable <scp>mPEG</scp> ‐ <scp>P4HB</scp> Nanoparticles for Curcumin Delivery in Cancer Therapy

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.