Cholesterol-conjugated poly(D, L-lactide)-based micelles as a nanocarrier system for effective delivery of curcumin in cancer therapy

Abstract

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
• cholesterol
• curcumin
• mPEG–PLA-Ch
• cancer

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. The work was supported in part by the grants provided by the Department of Science and Technology (CS-269/2013) and Department of Biotechnology (BT/Bio-CARe/07/10003/2013-14), Government of India to Swati Biswas. Preeti Kumari gratefully acknowledges INSPIRE (IF130703), Department of Science and Technology (DST), Ministry of Science and Technology, Government of India for awarding her with the Senior Research Fellowship.

Supplementary material available online.