Dual cross-linked chitosan/alginate hydrogels prepared by Nb-Tz 'click' reaction for pH responsive drug delivery

Huong Thi Hoang; Trung Thang Vu; Viswanathan Karthika; Sung-Han Jo; Yi-Jun Jo; Jeong-Woo Seo; Chul-Woong Oh; Sang-Hyug Park; Kwon Taek Lim

doi:10.1016/j.carbpol.2022.119389

Dual cross-linked chitosan/alginate hydrogels prepared by Nb-Tz 'click' reaction for pH responsive drug delivery

Carbohydr Polym. 2022 Jul 15:288:119389. doi: 10.1016/j.carbpol.2022.119389. Epub 2022 Mar 23.

Authors

Huong Thi Hoang¹, Trung Thang Vu¹, Viswanathan Karthika², Sung-Han Jo³, Yi-Jun Jo¹, Jeong-Woo Seo³, Chul-Woong Oh⁴, Sang-Hyug Park³, Kwon Taek Lim⁵

Affiliations

¹ Department of Smart Green Technology Engineering, Pukyong National University, Busan 48513, South Korea.
² Department of Display Engineering, Pukyong National University, Busan 48513, South Korea.
³ Department of Biomedical Engineering, Pukyong National University, Busan 48513, South Korea; Department of Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan 48513, South Korea.
⁴ Department of Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan 48513, South Korea; Department of Marine Biology, Pukyong National University, Busan 48513, South Korea.
⁵ Department of Smart Green Technology Engineering, Pukyong National University, Busan 48513, South Korea; Department of Display Engineering, Pukyong National University, Busan 48513, South Korea. Electronic address: ktlim@pknu.ac.kr.

PMID: 35450650
DOI: 10.1016/j.carbpol.2022.119389

Abstract

A novel physically and chemically double-crosslinked hydrogel derived from chitosan oligosaccharide/alginate (COS/Alg) was developed by using norbornene (Nb)-tetrazine (Tz) click reaction for ketoprofen delivery. The properties of the hydrogel were evaluated by rheological, FTIR, TGA, XRD, SEM, swelling and drug release studies. The Nb-Tz chemical cross-linking facilitated outstanding hydrophobic drug loading (44% wt/wt of ketoprofen) and sustained release through a hydrophobic interaction mechanism between the drug and the used polysaccharides. The COS/Alg electrostatics network (10/10 of NH₂/COOH molar ratio) generated the pH responsiveness, suppressing the release in simulated gastric fluid (below 10% for 2 h) and enhancing the release in simulated intestinal fluids (up to 84% for 24 h). The prepared hydrogel was non-toxic to human HEK-293 cells (95% cell viability). This work opens up a potential approach for preparing hydrophilic hydrogels from natural polysaccharides that can be used in the delivery of hydrophobic drugs.

Keywords: Alginate; Chitosan-oligosaccharide; Click-reaction; Drug-delivery; Ketoprofen; pH-responsive.

MeSH terms

Alginates / chemistry
Chitosan* / chemistry
Drug Carriers / chemistry
Drug Delivery Systems
Drug Liberation
HEK293 Cells
Humans
Hydrogels / chemistry
Hydrogen-Ion Concentration
Ketoprofen*
Niobium
Norbornanes

Substances

Alginates
Drug Carriers
Hydrogels
Norbornanes
Niobium
2-norbornene
Chitosan
Ketoprofen