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• W3031736282 startingPage "119482" @default.
• W3031736282 abstract "Chemotherapy in drug-resistant cancers remains a challenge. Owing to associated poor bioavailability, oral administration of hydrophobic anticancer drugs like paclitaxel has been quite challenging, with the scenario being further complicated by Pgp efflux in drug-resistant tumours. We developed a novel nanocochleates (CPT) system encapsulating paclitaxel (PTX) to treat resistant colon cancer by oral administration. PTX encapsulated nanocochleates (PTX-CPT), made up of phosphatidylserine in size range of 350–600 nm with −20 ± 5.2 mV zeta potential were protected from degradation at acidic gastric pH and showed sustained PTX release over 48 h under intestinal pH condition. In vitro cytotoxicity studies on HCT-116 & HCT-15 cells (multi-drug resistant) established IC50 value of <10 and 69 nM, respectively, which was significantly lower when compared to commercial Taxol formulation. Further, the in vivo efficacy with five oral doses of 30 mg/kg PTX-CPT in an HCT-15 drug-resistant colon cancer xenograft mouse model showed more than 25 fold reduction in the tumour growth inhibition as compared to intravenous Taxol which showed just 1.94% inhibition. Interestingly, PTX-CPT treated mice also showed significantly lower proliferation index and microvessel density when compared to Taxol treated mice. Nanocochleates showed lower toxicity with at LD-50 value greater than 300 mg/kg as described in OECD 423 guideline. The enhanced efficacy of PTX-CPT speculated due to its internalization by active endocytosis, ability to escape Pgp efflux, and due to a combined effect of the pro-apoptotic and antiangiogenic role. Taken together, the results suggested the PTX-CPT a promising strategy for efficiently treating drug-resistant colon cancer orally." @default.
• W3031736282 created "2020-06-05" @default.
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• W3031736282 date "2020-08-01" @default.
• W3031736282 modified "2023-09-27" @default.
• W3031736282 title "Enhanced absorption, and efficacy of oral self-assembled paclitaxel nanocochleates in multi-drug resistant colon cancer" @default.
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• W3031736282 doi "https://doi.org/10.1016/j.ijpharm.2020.119482" @default.
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