Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery

Abstract Many chemotherapeutics suffer from poor aqueous solubility and tissue selectivity. Distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) micellesare a promising formulation strategy for the delivery of hydrophobic anticancer drugs. However, storage and in vivo instability restrict their use. The aim of this study was to prepare mixed micelles, containing a novel polymer, lipoic acid-chitosan-poly(ethylene glycol) (LACPEG), and DSPE-PEG, to overcome these limitations and potentially increase cancer cell internalisation. Drug-loaded micelleswere prepared with a model tyrosine kinase inhibitor and characterized for size, surface charge, stability, morphology, drug entrapmentefficiency, cell viability (A549 and PC-9 cell lines), in vivo biodistribution, ex vivo tumor accumulation and cellular internalisation. Micellesof size 30–130 nm with entrapmentefficiencies of 46–81% were prepared. LACPEG/DSPE-PEG mixed micellesshowed greater interaction with the drug (condensing to half their size following entrapment), greater stability, and a safer profile in vitro compared to DSPE-PEG micelles. LACPEG/DSPE-PEG and DSPE-PEG micelleshad similar entrapmentefficiencies and in vivo tumor accumulation levels, but LACPEG/DSPE-PEG micellesshowed higher tumor cell internalisation. Collectively, these findings suggest that LACPEG/DSPE-PEG mixed micellesprovide a promising platform for tumor delivery of hydrophobic drugs.