In the present study, polymeric nanoparticles loaded with IRI and quercetin, a p-gp inhibitor, were developed to target folate receptors expressed by colon cancer cells for oral targeted delivery. This work reports the development of PNPs with an entrapment efficiency of 41.26 ± 0.56 % for IRI and 55.83 ± 4.51 for QT. PNPs were further surface modified using chitosan-folic acid conjugates for better targetability to obtain folic acid-chitosan coated nanoparticles. DLS and FeSEM revealed particles in the nanometric size range with spherical morphology, while FTIR and DSC provided details on their structure and encapsulation. In vitro drug release studies confirmed a sustained release pattern of IRI and QT, while cell line studies confirmed the superiority of C-FA-PNPs when tested on Caco2 cells. Pharmacodynamic studies in colon cancer induced rats showed similar efficacy for PNPs and C-FA-PNPs. Further examination from a bio-distribution study in healthy rats, revealed the failure of C-FA-PNPs to deliver the drugs to the colon adequately, while the PNPs improved the available concentration of IRI at the colon by almost 1.8 folds when compared to the available marketed product. Hence, the developed PNP formulation sticks out as a plausible substitute for the intravenous dosage forms of IRI which have been conventionally prevailing.
Keywords: Co-delivery; Design of experiments; Irinotecan; P-glycoprotein; Polymeric nanoparticles; Quercetin; cancer; colon.
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