Pluronic-coated hydroxypropyl-β-cyclodextrin nanoparticle potentiated chemotherapy on multidrug resistance cancer cells via improved docetaxel loading and P-glycoprotein inhibition

In the pharmaceutical formulation of anticancer drugs, US FDA-approved cyclodextrin (CD) and its derivates have been widely employed. Among them, hydroxypropyl β-cyclodextrin (HPCD) has attracted considerable attention owing to low toxicity, improved water solubility, and enhanced drug absorption; however, HPCD exhibits low drug loading efficiency and poor anticancer efficacy in multidrug-resistant (MDR) cancer cells. Therefore, to improve the drug loading efficiency and simultaneously overcome the MDR effects, we developed docetaxel (DTX)-loaded Pluronic®(PLU)-coated hydroxypropyl-β-cyclodextrin nanoparticles (DTX@PLU/HPCD NPs). We employed a simple nanoprecipitation technique, wherein PLU acted as a P-glycoprotein inhibitor to overcome MDR and an enhancer to achieve high drug loading. The HPCD NPs were coated with PLU (PF127, PP123, and PL81) of varying hydrophilic/lipophilic balance values, and the amount of encapsulated DTX was optimized. The DTX-loaded HPCD formulations (DTX@HPCD NP, DTX@PF127/HPCD NP, and DTX@PP123/HPCD NP) exhibited good stability and facilitated sustained release. The HPCD formulations exerted no cytotoxicity against examined cancer cell lines (HCT15 and SCC 7). DTX@PLU/HPCD NPs exerted potent anticancer effects in vitro. Notably, DTX@PP123/HPCD NPs significantly reduced the tumor volume in a mouse model. Collectively, these results indicate that PLU/HPCD NPs could function as drug carriers to alleviate toxicity and overcome MDR in various cancer models. [Display omitted]