Polypseudorotaxane and polydopamine linkage-based hyaluronic acid hydrogel network with a single syringe injection for sustained drug delivery. (15th August 2021)

• Record Type: Journal Article
• Authors: Hwang, ChaeRim; Lee, Song Yi; Kim, Han-Jun; Lee, KangJu; Lee, Junmin; Kim, Dae-Duk; Cho, Hyun-Jong
• Is Part Of: Carbohydrate polymers. Volume 266(2021)
• Publication Date: 2021-08-15
• Subjects: Crosslinked hydrogel -- Polypseudorotaxane -- Polydopamine -- Single syringe injection -- Slow biodegradation -- Sustained drug release; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2021.118104
• Languages: English
• ISSNs: 0144-8617

Abstract

Abstract: Polypseudorotaxane structure and polydopamine bond-based crosslinked hyaluronic acid (HA) hydrogels including donepezil-loaded microspheres were developed for subcutaneous injection. Both dopamine and polyethylene glycol (PEG) were covalently bonded to the HA polymer for catechol polymerization and inclusion complexation with alpha-cyclodextrin (α-CD), respectively. A PEG chain of HA-dopamine-PEG (HD-PEG) conjugate was threaded with α-CD to make a polypseudorotaxane structure and its pH was adjusted to 8.5 for dopamine polymerization. Poly(lactic- co -glycolic acid) (PLGA)/donepezil microsphere (PDM) was embedded into the HD-PEG network for its sustained release. The HD-PEG/α-CD/PDM 8.5 hydrogel system exhibited an immediate gelation pattern, injectability through single syringe, self-healing ability, and shear-thinning behavior. Donepezil was released from the HD-PEG/α-CD/PDM 8.5 hydrogel in a sustained pattern. Following subcutaneous injection, the weight of excised HD-PEG/α-CD/PDM 8.5 hydrogel was higher than the other groups on day 14. These findings support the clinical feasibility of the HD-PEG/α-CD/PDM 8.5 hydrogel for subcutaneous injection. Highlights: Hyaluronic acid-dopamine-polyethylene glycol (HD-PEG) was synthesized and identified. HD-PEG was threaded with alpha-cyclodextrin (α-CD) and pH was adjusted to 8.5. Polypseudorotaxane structure and polydopamine bond-based hydrogel was fabricated. Donepezil-loaded microspheres were embedded in hydrogel system for sustained release. Rheological features of injectable hydrogel were tuned for slow biodegradation.