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 mm versus 1174.68 ± 1.64 mm) 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.

Cholesterol-coated gold nanorods as an efficient nano-carrier for chemotherapeutic delivery and potential treatment of breast cancer: in vitro studies using the MCF-7 cell line

“…45 Moreover, cholesterol-coupled to poly(D,L-lactide)-micelles were used for efficient delivery of curcumin into melanoma and breast cancer cell. 46 3.7 Analysis of cell death modality of MCF-7 cells upon treatment with Chol-A-GNRs by ow cytometry 3.7.1 Apoptosis analysis. To determine cell death modality, MCF-7 cells pre-treated with nanocomplex (Chol-A-GNRs) were examined aer 24 h of treatment using ow cytometry.…”

Cholesterol and vitamin E-conjugated PEGylated polymeric micelles for efficient delivery and enhanced anticancer activity of curcumin: evaluation in 2D monolayers and 3D spheroids

“…CMC was determined using pyrene incorporation method as reported previously [24]. Briefly, chloroform solution of pyrene (10 mg/mL) was divided into 50 lL aliquots and transferred to 5 mL glass tubes.…”

“…The release occurred in two phases, that is, initial burst release (>20%) followed by second phase of sustained release. Initial burst release could be due to the location of curcumin at the interface between the micelle core and shell [24]. The sustained drug release could be due to the compatibility of Cur with the sufficiently hydrophobic core.…”

Zinc Oxide Composites of Doxorubicin in the Form of Coating, Composite Films and Gels with a High Antitumor Activity and Low Toxicity

“…-nanoparticles containing organic and polymeric molecules as basic structural elements [5][6][7][8][9][10]; -nanoparticles containing inorganic substances, usually metals, metal oxides as basic elements [11][12][13][14].…”