Multi-drug delivery to tumor cells via micellar nanocarriers

Abstract

The aim of this study was to develop micellar nanocarriers for concomitant delivery of paclitaxel and 17-allylamino-17-demethoxygeldanamycin (17-AAG) for cancer therapy. Paclitaxel and 17-AAG were simultaneously loaded into polymeric micelles by a solvent evaporation method. Two candidate nanocarrier constructs, polyethylene glycol-poly(D, L-lactic acid) (PEG-PLA) micelles and PEG-distearoylphosphatidylethanolamine/tocopheryl polyethylene glycol 1000 (PEG-DSPE/TPGS) mixed micelles, were assessed for the release kinetics of the loaded drugs. Compared to PEG-PLA micelles, entrapment of paclitaxel and 17-AAG into PEG-DSPE/TPGS mixed micelles resulted in significantly prolonged release half-lives. The simultaneous incorporation of paclitaxel and 17-AAG into PEG-DSPE/TPGS mixed micelles was confirmed by 1H NMR analysis. Paclitaxel/17-AAG-loaded PEG-DSPE/TPGS mixed micelles were as effective in blocking the proliferation of human ovarian cancer SKOV-3 cells as the combined free drugs. PEG-DSPE/TPGS mixed micelles may provide a novel and advantageous delivery approach for paclitaxel/17-AAG combination therapy.

EGFR-targeted poly(ethylene glycol)-distearoylphosphatidylethanolamine micelle loaded with paclitaxel for laryngeal cancer: preparation, characterization andin vitroevaluation

“…We further carried out the release study in the presence of serum proteins to mimic in vivo circulation environment (Katragadda et al, 2011). In brief, 0.3 ml paclitaxel-loaded micelles were diluted in 2.7 ml fetal bovine serum and loaded into the dialysis bag with molecular weight cutoff of 20 000 Da (Sigma).…”

Multidrug PLA-PEG filomicelles for concurrent delivery of anticancer drugs—The influence of drug-drug and drug-polymer interactions on drug loading and release properties

“…Co-incorporation of two or three hydrophobic drugs in micelles has already been reported (Aw et al, 2013;Katragadda et al, 2013;Katragadda et al, 2011). PLA-PEG micelles containing paclitaxel (Ptx), 17-AAG and rapamycin (Rap) known as Triolimus present a 10 to 10,000-fold increase in aqueous solubility of drugs, and display potent cytotoxic synergy in vitro and antitumor activity in vivo Hasenstein et al, 2012).…”

Polymeric Micelles for Multi-Drug Delivery in Cancer

“…d e t a i l e d P E Gdistearoylphosphatidylethanolamine/tocopheryl PEG (PEG-DSPE/TPGS) mixed micelles physically carrying both PTX and 17-AAG and emphasized the superior benefits of dualdrug-loading polymeric micelles over free drugs dissolved in solvent (56). Systemically delivered PEG-DSPE/TPGS micelles dual-loaded with PTX (20 mg/kg) and 17-AAG (37.5 mg/kg) resulted in ten-fold increase of PTX level and threefold increase of 17-AAG level in plasma in comparison with free PTX and 17-AAG.…”