Injectable depot forming thermoresponsive hydrogel for sustained intrascleral delivery of sunitinib using hollow microneedles

Shilpkala Shankar Gade, Sreekanth Pentlavalli, Deepakkumar Mishra, Lalitkumar K. Vora, David Waite, Carmen Isabel Alvarez-Lorenzo, Maria Roccio Herrero Vanrell, Garry Laverty, Eneko Larrañeta, Ryan F. Donnelly, Raghu Raj Singh Thakur*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)
102 Downloads (Pure)

Abstract

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 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.
Original languageEnglish
Pages (from-to)433-448
JournalJournal of Ocular Pharmacology and Therapeutics
Volume38
Issue number6
Publication statusPublished - 01 Aug 2022

Keywords

  • Animals
  • Chitosan - chemistry
  • Drug Delivery Systems
  • Hydrogels - chemistry
  • Sunitinib
  • Swine
  • Temperature
  • age-related macular degeneration
  • chitosan
  • grafting
  • poly(n-isopropylacrylamide)
  • sunitinib
  • thermoresponsive hydrogel

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