Polylactide-Cholesterol Stereocomplex Micelle Encapsulating Chemotherapeutic Agent for Improved Antitumor Efficacy and Safety.

For efficient therapy, optimized polymer micelle drug delivery systems require stability during circulation, appropriate diameters for targeting, and controlled drug release at the lesion site. To enhance the stability, adjust the sizes, and improve the selectivity of drug release of micelles from polylactides and polypeptides, stereocomplex interaction has been introduced. Herein, the cholesterol (CHOL)-enhanced doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (CDM/DOX), poly(L-lactide)-based micelle (CLM/DOX), and stereocomplex micelle (SCM/DOX) from the equimolar mixture of the enantiomeric 4-armed poly(ethylene glycol)-polylactide copolymers were reported to enhance tumor cell uptake and control drug release for treatment of cervical carcinoma. The introduction of hydrophobic CHOL further upregulated the stability, drug-loading capability, and cell uptake of micelles. All these DOX-loaded micelles showed appropriate sizes of ∼100 nm for the enhanced permeability and retention (EPR) effect. Compared to CDM/DOX and CLM/DOX, SCM/DOX exhibited the highest cell uptake and the most efficient antitumor efficacy in vitro . For U14 cervical carcinoma mouse model, all of the DOX-loaded micelles, especially SCM/DOX, effectively inhibited the progression of cervical carcinoma, as demonstrated by nearly stagnant tumor growth and increased apoptosis and necrosis areas within tumor tissue. Furthermore, these DOX-loaded micelles effectively alleviated the systemic toxicity of DOX. All the above results suggest that the DOX-loaded micelles, especially SCM/DOX, are an ideal drug delivery system for combating cervical carcinoma.