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

Niyaz Ahmad; Rizwan Ahmad; Ridha Abdullah Alrasheed; Hassan Mohammed Ali Almatar; Abdullah Sami Al-Ramadan; Taysser Mohammed Buheazah; Hussain Salman AlHomoud; Hassan Ali Al-Nasif; Md Aftab Alam

doi:10.1016/j.sjbs.2020.05.023

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

Saudi J Biol Sci. 2020 Sep;27(9):2344-2357. doi: 10.1016/j.sjbs.2020.05.023. Epub 2020 May 20.

Authors

Niyaz Ahmad^{1

2}, Rizwan Ahmad³, Ridha Abdullah Alrasheed¹, Hassan Mohammed Ali Almatar¹, Abdullah Sami Al-Ramadan¹, Taysser Mohammed Buheazah¹, Hussain Salman AlHomoud¹, Hassan Ali Al-Nasif¹, Md Aftab Alam⁴

Affiliations

¹ Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
² Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
³ Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
⁴ Department of Pharmaceutics, School of Medical and Allied Sciences, Galgotias University, Gautam Budh Nagar, Greater Noida 201310, India.

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 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 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 C_max with AUC_0-24 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.

Keywords: 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, liquid–liquid 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.