A Chitosan-PLGA based catechin hydrate nanoparticles used in targeting of lungs and cancer treatment

摘要

Objective To prepare a novel Chitosan (CS)-coated-PLGA-NPs of catechin hydrate (CTH) and to improve lungs bioavailability via direct nose to lungs-delivery for the comparative assessment of a pulmokinetics study by the first-time UHPLC-MS/MS developed method in the treatment of lungs cancer via anticancer activities on H1299 lung cancer cells. Material and methods PLGA-NPs was prepared by solvent evaporation (double emulsion) method followed by coated with chitosan (CS) and evaluated based on release and permeation of drug, a comparative pulmokinetics study with their anticancer activities on H1299 lung cancer cells. Results The particle size, PDI and ZP of the optimized CAT-PLGA-NPs and CS-CAT-PLGA-NPs were determined 124.64?±?12.09?nm and 150.81?±?15.91?nm, 0.163?±?0.03 and 0.306?±?0.03, –3.94?±?0.19?mV and 26.01?±?1.19?mV respectively. Furthermore, higher entrapment efficiency was observed for CS-CAT PLGA NPs. The release pattern of the CS-CAT-PLGA NPs was found to favor the release of entrapped CAT within the cancer microenvironment. CS-CAT-PLGA-NPs exposed on H1299 cancer cells upto 24.0?h was found to be higher cytotoxic as compared to CAT-solution (CAT-S). CS-CAT-PLGA-NPs showed higher apoptosis of cancer cells after their exposure as compared to CAT-S. CS-CTH-PLGA-NPs showed tremendous mucoadhesive-nature as compared to CTH-S and CS-CTH-PLGA NPs by retention time (RT) of 0.589?min, and m / z of 289.21/109.21 for CTH alongwith RT of 0.613?min and m / z of 301.21/151.21 was found out for IS (internal standard), i.e. Quercetin). Likewise, for 1–1000?ng?mLsup?1/sup (linear range) of % accuracy (92.01–99.31%) and %CV (inter & intra-day, i.e. 2.14–3.33%) was determined. The improved Csubmax/sub with AUCsub0–24/sub was observed extremely significant (p??0.001) via i.n. as compared oral and i.v. in the wistar rat’s lungs. The CS-approach was successfully designed and safely delivered CAT to the lungs without causing any risk. Conclusion CS-CTH-PLGA-NPs were showed a significant role (p??0.001) for the enhancement of lungs-bioavailability and potentially promising approach to treat lung cancers. CS-CTH-PLGA-NPs did not cause any toxicity, it showed safety and have no obvious toxic-effects on the rat’s lungs and does not produce any mortality followed by no abnormal findings in the treated-rats.