A Chitosan-PLGA based catechin hydrate nanoparticles used in targeting of lungs and cancer treatment.
Saudi J Biol Sci
; 27(9): 2344-2357, 2020 Sep.
Article
en En
| MEDLINE
| ID: mdl-32884416
ABSTRACT
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 ANDMETHODS:
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⯱â¯12.09â¯nm and 150.81⯱â¯15.91â¯nm, 0.163⯱â¯0.03 and 0.306⯱â¯0.03, -3.94⯱â¯0.19â¯mV and 26.01⯱â¯1.19â¯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 24.0â¯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 0.589â¯min, and m/z of 289.21/109.21 for CTH alongwith RT of 0.613â¯min and m/z of 301.21/151.21 was found out for IS (internal standard), i.e. Quercetin). Likewise, for 1-1000â¯ngâ¯mL-1 (linear range) of % accuracy (92.01-99.31%) and %CV (inter & intra-day, i.e. 2.14-3.33%) was determined. The improved Cmax with AUC0-24 was observed extremely significant (pâ¯<â¯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 (pâ¯<â¯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.
ANOVA, analysis of variance; AUC, area under curve; Apoptosis; CC, calibration curve; CH-S, catechin-hydrate-suspension; CS, chitosan; CS-CTH-PLGA-NPs; CS-CTH-PLGA-NPs, chitosan-coated catechin hydrate-loaded-PLGA-nanoparticles; CTH, Catechin hydrate; Catechin hydrate; Cmax, maximum plasma concentration; DCM, dichloromethane; DSC, differential scanning calorimetry; EE, entrapment efficiency; ESI, Electrospray ionization; HQC, high quality control; IS, internal standard; Kel, elimination rate constant; LC, loading capacity; LLOQ, liquidliquid extraction: LLE: lower limit of quantification; LLOQQC, lower limit of quantification for quality control; LOD, lower limit of detection; LOQ, lower limit of quantitation; Lung cancer; Lungs comparative pulmokinetics; MQC, low quality control: LQC: middle quality control; NPs, nanoparticles; PBS, phosphate buffered solution; PDI, polydispersity index; PVA, polyvinyl alcohol; SEM, scanning electron microscope; TEM, transmission electron microscope; Tmax, time to Cmax; UHPLC-MS/MS; UHPLC-MS/MS, ultra high performance liquid chromatography mass spectroscopy and mass spectroscopy; t½, half-life
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Bases de datos:
MEDLINE
Idioma:
En
Revista:
Saudi J Biol Sci
Año:
2020
Tipo del documento:
Article
País de afiliación:
Arabia Saudita