Linolenic acid-modified PEG-PCL micelles for curcumin delivery

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Curcumin, a natural compound, exhibits poor water solubility and bioavailability, limiting its therapeutic applications.
• Developing effective delivery systems is crucial to overcome curcumin's limitations and enhance its anticancer potential.

Purpose of the Study:

• To synthesize and characterize a novel linolenic acid-modified poly(ethylene glycol)-b-poly(ϵ-caprolactone) copolymer.
• To develop curcumin-loaded micelles using this copolymer as a drug delivery system.
• To evaluate the physicochemical properties, in vitro release, in vivo pharmacokinetics, and safety of the curcumin-loaded micelles.

Main Methods:

• Copolymer synthesis via radical addition, ring-opening polymerization, and N-acylation.
• Micelle formation using the thin-film hydration method.
• Characterization using NMR, GPC, XRD, and FT-IR.
• In vitro drug release, cytotoxicity, hemolysis, and intravenous irritation tests.
• In vivo pharmacokinetic studies in rats.

Main Results:

• The modified copolymer successfully formed spherical micelles with high curcumin loading (12.80%) and entrapment efficiency (98.53%).
• Curcumin solubility increased significantly, and its release was controlled, with reduced release rate compared to unmodified micelles.
• Enhanced anticancer activity was observed, attributed to π-π conjugation and reduced release.
• The modified copolymer demonstrated safety for intravenous injection.
• In vivo studies showed a significant increase in curcumin's AUC0-∞ and MRT0-∞, indicating improved bioavailability.

Conclusions:

• Linolenic acid-modified PEG-b-PCL copolymer is a promising carrier for curcumin delivery.
• The developed micelles enhance curcumin's solubility, stability, and bioavailability.
• The modification improves curcumin's anticancer efficacy and safety profile for intravenous administration.