2021_Development of Colonic Targeting Insulin-Loaded Trimethyl Chitosan Nanoparticles Coated with Pectin for Oral Delivery
| Format: | General Document |
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| building | INTELEK Repository |
| collection | Online Access |
| collectionurl | https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection3 |
| copyright | Copyright©PWB2025 |
| country | Malaysia |
| date | 2022-02-07 |
| format | General Document |
| id | 15369 |
| institution | UniSZA |
| internalnotes | Sila masukkan subject wajib Dissertations, Academic. Terima kasih... |
| originalfilename | 15369_a8d214e453faed7.pdf |
| person | Salma Seyam Ramadan Ahmed Sayed |
| recordtype | oai_dc |
| resourceurl | https://intelek.unisza.edu.my/intelek/pages/view.php?ref=15369 |
| sourcemedia | Server storage Scanned document |
| spelling | 15369 https://intelek.unisza.edu.my/intelek/pages/view.php?ref=15369 https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection3 General Document Malaysia Library Staff (Top Management) Library Staff (Management) Library Staff (Support) Terengganu Faculty of Pharmacy English application/pdf 1.5 Server storage Scanned document Universiti Sultan Zainal Abidin UniSZA Private Access Universiti Sultan Zainal Abidin SAMBox 2.3.4; modified using iTextSharp™ 5.5.10 ©2000-2016 iText Group NV (AGPL-version) 2022-02-07 15369_a8d214e453faed7.pdf 154 2021_Development of Colonic Targeting Insulin-Loaded Trimethyl Chitosan Nanoparticles Coated with Pectin for Oral Delivery Salma Seyam Ramadan Ahmed Sayed Colonic Drug Delivery Copyright©PWB2025 While oral insulin administration seems to be favorable and more convenient to diabetic patients, subcutaneous injection is still the most common insulin therapy route. In contrast to the parenteral route, oral insulin delivery mimics the physiological pathway of endogenous insulin secretion. Nevertheless, oral insulin has poor bioavailability (less than 2%) due to the harsh physiological environment within the gastrointestinal tract (GIT). This study aims to synthesize insulin-loaded trimethyl chitosan nanoparticles coated with a colon-specific layer of pectin as a potential carrier for colon-targeted oral insulin delivery. Pectin was used to protect insulin-loaded nanoparticles from degradation in the stomach and small intestine, while trimethyl chitosan (TMC) enhances cellular uptake by reversibly opening the tight junctions between the epithelial cells at absorption site. TMC was synthesised via two-steps reductive methylation process. The synthesis of TMC was confirmed by Fourier Transform Infrared (FT-IR) and Nuclear Magnetic Resonance (NMR) spectroscopy. Blank chitosan nanoparticles (CSNPs) were first optimized by studying the effect of chitosan concentration, TPP concentration, and pH of chitosan solution as formulation parameters, and stirring time, stirring speed and TPP addition flow rate as operational parameters on the obtained nanoparticles. Then, three types of insulin-loaded nanoparticles; insulin-loaded CSNPs, insulin-loaded trimethyl chitosan nanoparticles (TMC-NPs) and insulin-loaded pectin trimethyl chitosan nanoparticles (P-TMC-NPs) were fabricated by ionotropic gelation method. The obtained nanoparticles were characterised in terms of the size, polydispersity index (PDI) and zeta potential by means of dynamic light scattering (DLS). Loading efficiency and cumulative drug release of the nanoparticles were investigated by ultraviolet-visible (UV-Vis) spectrophotometry. MTT assay was used to evaluate the cytotoxicity of the optimal formulations in-vitro using HT-29 cells. CSNPs and TMC-NPs with reduced particle size and improved loading efficiency were successfully prepared by ionic gelation method. The size and loading efficiency of TMC-NPs were significantly improved (244.43 ± 10.34 nm, 71.19 ± 0.74%) compared to CSNPs (279.36 ± 32.03 nm, 57.1 ± 3.30%). The particle size and PDI of P-TMC NPs were 379.4 ± 40.26 nm, 24.1 ± 1.03 % with zeta potential and loading efficiency of 17.2 ± 0.52 mV and 83.21 ± 1.23%, respectively. P-TMC-NPs were able to protect and control insulin release in the simulated gastric fluid (SGF). A significant low cumulative release of insulin in SGF (<14%), while uncoated CS and TMC nanoparticles showed rapid release of insulin in first 2 hours (92.5 ± 0.65% and 81.63 ± 0.46% respectively). MTT assay revealed that all insulin-loaded formulations were considered non-toxic toward HT-29 cells. The three formulations with different concentrations at 100, 300 and 500 µg/mL were characterised with low toxicity effect on the cell line (all values > 90.92 %) after 24 h of incubation. The results indicate that colon-targeted pectin-coated insulin-loaded TMC nanoparticles can be a promising system for oral insulin delivery. Dissertations, Academic Sila masukkan subject wajib Dissertations, Academic. Terima kasih... Trimethyl Chitosan Colonic Targeting Pectin-Coated Nanoparticles Thesis |
| spellingShingle | 2021_Development of Colonic Targeting Insulin-Loaded Trimethyl Chitosan Nanoparticles Coated with Pectin for Oral Delivery |
| state | Terengganu |
| subject | Colonic Drug Delivery Dissertations, Academic |
| summary | While oral insulin administration seems to be favorable and more convenient to diabetic patients, subcutaneous injection is still the most common insulin therapy route. In contrast to the parenteral route, oral insulin delivery mimics the physiological pathway of endogenous insulin secretion. Nevertheless, oral insulin has poor bioavailability (less than 2%) due to the harsh physiological environment within the gastrointestinal tract (GIT). This study aims to synthesize insulin-loaded trimethyl chitosan nanoparticles coated with a colon-specific layer of pectin as a potential carrier for colon-targeted oral insulin delivery. Pectin was used to protect insulin-loaded nanoparticles from degradation in the stomach and small intestine, while trimethyl chitosan (TMC) enhances cellular uptake by reversibly opening the tight junctions between the epithelial cells at absorption site. TMC was synthesised via two-steps reductive methylation process. The synthesis of TMC was confirmed by Fourier Transform Infrared (FT-IR) and Nuclear Magnetic Resonance (NMR) spectroscopy. Blank chitosan nanoparticles (CSNPs) were first optimized by studying the effect of chitosan concentration, TPP concentration, and pH of chitosan solution as formulation parameters, and stirring time, stirring speed and TPP addition flow rate as operational parameters on the obtained nanoparticles. Then, three types of insulin-loaded nanoparticles; insulin-loaded CSNPs, insulin-loaded trimethyl chitosan nanoparticles (TMC-NPs) and insulin-loaded pectin trimethyl chitosan nanoparticles (P-TMC-NPs) were fabricated by ionotropic gelation method. The obtained nanoparticles were characterised in terms of the size, polydispersity index (PDI) and zeta potential by means of dynamic light scattering (DLS). Loading efficiency and cumulative drug release of the nanoparticles were investigated by ultraviolet-visible (UV-Vis) spectrophotometry. MTT assay was used to evaluate the cytotoxicity of the optimal formulations in-vitro using HT-29 cells. CSNPs and TMC-NPs with reduced particle size and improved loading efficiency were successfully prepared by ionic gelation method. The size and loading efficiency of TMC-NPs were significantly improved (244.43 ± 10.34 nm, 71.19 ± 0.74%) compared to CSNPs (279.36 ± 32.03 nm, 57.1 ± 3.30%). The particle size and PDI of P-TMC NPs were 379.4 ± 40.26 nm, 24.1 ± 1.03 % with zeta potential and loading efficiency of 17.2 ± 0.52 mV and 83.21 ± 1.23%, respectively. P-TMC-NPs were able to protect and control insulin release in the simulated gastric fluid (SGF). A significant low cumulative release of insulin in SGF (<14%), while uncoated CS and TMC nanoparticles showed rapid release of insulin in first 2 hours (92.5 ± 0.65% and 81.63 ± 0.46% respectively). MTT assay revealed that all insulin-loaded formulations were considered non-toxic toward HT-29 cells. The three formulations with different concentrations at 100, 300 and 500 µg/mL were characterised with low toxicity effect on the cell line (all values > 90.92 %) after 24 h of incubation. The results indicate that colon-targeted pectin-coated insulin-loaded TMC nanoparticles can be a promising system for oral insulin delivery. |
| title | 2021_Development of Colonic Targeting Insulin-Loaded Trimethyl Chitosan Nanoparticles Coated with Pectin for Oral Delivery |
| title_full | 2021_Development of Colonic Targeting Insulin-Loaded Trimethyl Chitosan Nanoparticles Coated with Pectin for Oral Delivery |
| title_fullStr | 2021_Development of Colonic Targeting Insulin-Loaded Trimethyl Chitosan Nanoparticles Coated with Pectin for Oral Delivery |
| title_full_unstemmed | 2021_Development of Colonic Targeting Insulin-Loaded Trimethyl Chitosan Nanoparticles Coated with Pectin for Oral Delivery |
| title_short | 2021_Development of Colonic Targeting Insulin-Loaded Trimethyl Chitosan Nanoparticles Coated with Pectin for Oral Delivery |
| title_sort | 2021_development of colonic targeting insulin-loaded trimethyl chitosan nanoparticles coated with pectin for oral delivery |