| Autor: |
Gade SS; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, United Kingdom., Pentlavalli S; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, United Kingdom., Mishra D; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, United Kingdom., Vora LK; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, United Kingdom., Waite D; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, United Kingdom., Alvarez-Lorenzo CI; Departamento de Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela, Spain., Herrero Vanrell MR; Departmento de Farmacia Galenica y Technologia Alimmentatia, Facultad de farmacia, Universidad Complutense de Madrid, Madrid, Spain., Laverty G; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, United Kingdom., Larraneta E; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, United Kingdom., Donnelly RF; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, United Kingdom., Thakur RRS; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, United Kingdom. |
| Abstrakt: |
Purpose: Age-related macular degeneration is a vision-threatening disorder affecting the posterior segment of the eye. Drug delivery to the posterior segment is challenging owing to the complex anatomical and physiological structure, necessitating monthly injections of antivascular endothelial growth factors. Thermoresponsive hydrogels provide sustained drug delivery and ease of injection, due to their sol-gel transition. Poly (N-isopropyl acrylamide) (PNIPAAm) is a widely researched thermoresponsive hydrogel; however, insufficient wet strength and a wide mesh network make it inept for the entrapment of small molecules. Methods: A novel approach of grafting PNIPAAm with chitosan is exploited. A chitosan concentration altered in 10%, 30%, and 50% compared to PNIPAAm is investigated for entrapment of a small-molecular weight, hydrophilic drug, sunitinib (SUN), a multiple tyrosine kinase receptor inhibitor. Furthermore, these hydrogels were characterized using 1 H-NMR, FTIR, differential scanning calorimetry (DSC), and thermogravimetric analysis for chemical characterization and viscosity, swellability, syringeability, degradation, and In-vitro permeation using Franz-diffusion cell. Results: In-vitro drug release kinetics suggested that the release of SUN could be controlled with the percentage of chitosan grafting; however, gel strength (3%-5% w/v) of 30% Cs-g-PNIPAAm did not significantly affect percentage drug release. Sustained release of SUN was observed for 1 month. In-vitro permeation studies on porcine sclera suggested that a thermoresponsive gel of chitosan grafted PNIPAAm (Cs-g-PNIPAAm) was able to sustain the drug release by 40%, compared to SUN solution. Conclusions: The study indicates that the synthesized Cs-g-NIPAAm hydrogel has the potential to serve as a tailorable injectable platform for intrascleral drug delivery applications. |
