Abstract
Multiple drug resistance (MDR) hampers therapeutic outcome of many anti-cancer drugs, including doxorubicin (Dox) by reducing their intracellular concentration at sub-therapeutic level. Vitamin-E/derivatives proved to sensitize cancer cells towards treatment by inhibiting MDR proteins. Here, previously synthesized α-tocopheryl succinate (α-TOS), poly(ethylene glycol) (PEG) and dioleoyl Phosphatidyl ethanolamine (DOPE) conjugated star shaped amphiphilic polymer, where three polymeric components were attached via lysine linker, was used to prepare micelles (VPM) to load the MDR-inducing chemotherapeutic agent, Doxorubicin. The micelles were subjected to physico-chemical characterizations, including hydrodynamic radius and polydispersity index (PDI) to assess formation of stable nanoparticles, zeta potential to measure the surface charge, encapsulation efficiency and drug loading to check effectivity of the nanocarrier system to carry the payload. Dox-loaded VPM (Dox-VPM) was evaluated in Dox resistant human colon carcinoma, SW 620-R and human breast adenocarcinoma, MDA MB-231-R cell lines. Dox-VPM demonstrated a particle size of 141.2 ± 0.78 nm with Dox-loading efficiency as 14.2 ± 0.19%. Time and concentration dependent cellular uptake was observed for Dox-VPM in both the cell lines. Dox-VPM exhibited significant cytotoxic action to both the resistant cancer cells. Dox-VPM exhibited superior therapeutic efficacy, which warrants further investigation of this nanomedicine in Dox-resistant cancers.
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