Reactive oxygen species-responsive thymine-conjugated chitosan: Synthesis and evaluation as cryogel.

Autor: Kulkarni N; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gujarat 382355, India., Shinde SD; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gujarat 382355, India., Maingle M; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gujarat 382355, India., Nikam D; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gujarat 382355, India., Sahu B; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gujarat 382355, India. Electronic address: bichismita@niperahm.res.in.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2023 Jul 01; Vol. 242 (Pt 3), pp. 125074. Date of Electronic Publication: 2023 May 26.
DOI: 10.1016/j.ijbiomac.2023.125074
Abstrakt: Chitosan (CS) is a biodegradable, biocompatible cationic polysaccharide based natural polymer with antibacterial and anti-inflammatory properties. Hydrogels made from CS have found their applications in wound healing, tissue regeneration and drug delivery. Although, mucoadhesive properties are resulted from the polycationic nature of CS, in hydrogel form amines are engaged in interactions with water leading to decrease in mucoadhesive properties. In case of injury, presence of elevated level of reactive oxygen species (ROS) has inspired many drug delivery platforms to conjugate ROS responsive linkers for on demand drug delivery. In this report we have conjugated a reactive oxygen species (ROS) responsive thioketal (Tk) linker and nucleobase thymine (Thy) with CS. Cryogel from this doubly functionalized polymer CS-Thy-Tk was prepared through crosslinking with sodium alginate. Inosine was loaded on the scaffold and studied for its release under oxidative condition. We anticipated that the presence of thymine shall retain the mucoadhesive nature of the CS-Thy-Tk polymer in hydrogel form and when placed at the site of injury, due to the presence of excessive ROS at inflammatory condition, loaded drug shall release due to degradation of the linker. Porous cryogel scaffold was prepared via chemical crosslinking of amine functional group of chitosan with carboxylic acid containing polysaccharide sodium alginate. The cryogel was evaluated for porosity (FE-SEM), rheology, swelling, degradation, mucoadhesive properties and biocompatibility. Resulted scaffold was found to be porous with average pore size of 107 ± 23 μm, biocompatible, hemocompatible and possesses improved mucoadhesive property (mucin binding efficiency of 19.54 %) which was found to be 4 times better as compared to chitosan (4.53 %). The cumulative drug release found to be better in the presence of H 2 O 2 (∼90 %) when compared to that of PBS alone (∼60-70 %) . Therefore, the modified CS-Thy-TK polymer may hold potential as interesting scaffold in case of conditions associated with elevated ROS level such as injury and tumor.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bichismita sahu reports a relationship with SERB-India that includes: funding grants and non-financial support.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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