Background: To develop a first-time-novel polymeric NPs from PLGA and their coating by Chitosan (CS) of Melatonin (MT) for the enhancement of lungs bioavailability by targeting lungs from the nose. Materials and Methods: The Melatonin LC-MS/MS method was developed for the first time for a comparative Pulmokinetic evaluation administered by different routes which will be useful for the treatment of lung cancer and in vitro evaluation on lung cancer cell-lines (H1299). The solvent evaporation method was used to develop the PLGA nanoparticles and their encapsulation by CS. Results: CS MT PLGA MPs were given a significantly high release and permeation of MT as compared to MT PLGA NPs. Different routes of administration were used to compare the pulmokinetics parameters. Lung cancer cell lines (H1299) were used for anticancer activities. PDI, ZP, PS, DL, and EE of CS MT PLGA NPs were observed at 0.131±0.009, +19.5±1.37mV, 98.36±7.15 nm, 4.19±0.38%, and 74.16 ± 5.29% respectively. Mucoadhesive nature of CS MT PLGA NPs was showed greater than MT PLGA NPs and MT S with 0.303 retention time with mas' spectra of 233.20/174.10. The developed method was linear (1-1000ng/mL) with inter and intra-day accuracy (91.68-98.95%) followed by precision (1.67-2.69%). C max and AUC 0-24 were significantly enhanced (p<0.001) than i.v. and oral in the lungs. Conclusion: Capping of CS on PLGA NPs could be a strong possible nanocarrier for Melatonin to enhance their solubility of a drug (MT), entrapment, sustain and controlled release, and stability, with their therapeutic application.
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