Polymeric micelles have been widely explored preclinically as suitable delivery systems for poorly soluble chemotherapeutic drugs in cancer therapy. The present study reported the development of cholesterol (Ch)-conjugated poly(D,L-Lactide) (PLA)-based polymeric micelles (mPEG-PLA-Ch) for effective encapsulation and delivery of curcumin (CUR) at the tumor site. Cholesterol conjugation dramatically affected the particle size and improved drug loading (DL) and encapsulation efficiency (EE). mPEG-PLA-Ch-CUR showed bigger hydrodynamic diameter (104.6 ± 2.1 nm, and 169.3 ± 1.52 nm for mPEG-PLA and mPEG-PLA-Ch, respectively) due to increased size of the hydrophobic core. The newly developed polymer exhibited low critical micelles concentration (CMC) (25 μg/mL) which is close to lipid-based polymer, PEG-phosphatidyl ethanolamine (12.5 μg/mL) compared to mPEG-PLA (50 μg/mL). mPEG-PLA-Ch micelles exhibited relatively higher EE (93.74 ± 1.6%) and DL (11.86 ± 0.8%) compared to mPEG-PLA micelles (EE 91.89 ± 1.2% and DL 11.06 ± 0.8%). mPEG-PLA-Ch micelles were internalized by the cancer cells effectively and exhibited higher cytotoxicity compared to free CUR in both, murine melanoma (B16F10) and human breast cancer (MDA-MB-231) cells. mPEG-PLA-Ch exhibited satisfactory hemocompatibility indicating their potential for systemic application. Further, mPEG-PLA-Ch-CUR demonstrated higher rate of reduction of tumor volume in B16F10-xenografted tumor-bearing mice compared to free CUR. At the end of 22 days, the tumor reduced to 1.87-fold (627.72 ± 0.9 mm3 versus 1174.68 ± 1.64 mm3) compared to the treatment with free CUR. In conclusion, the experimental data in vitro and in vivo indicated that the newly developed CUR-mPEG-PLA-Ch micelles may have promising applications in solid tumors.
Keywords: Polymeric micelles; cancer; cholesterol; curcumin; mPEG–PLA-Ch.