Monopotassium phosphate-reinforced in situ forming injectable hyaluronic acid hydrogels for subcutaneous injection

Monopotassium phosphate and pH modulation-reinforced hydrogel based on hyaluronic acid (HA) grafted with dopamine (dopa) was fabricated as one of subcutaneous injection formulations of donepezil (DPZ). Both incorporation of KH2PO4 and pH adjustment finally attributed to tuning viscoelastic and biode...

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Bibliographic Details
Published in:International journal of biological macromolecules 2020-11, Vol.163, p.2134-2144
Main Authors: Seo, Ji-Hye, Lee, Song Yi, Kim, Sungyun, Yang, Mingyu, Jeong, Da In, Hwang, ChaeRim, Kim, Min-Hwan, Kim, Han-Jun, Lee, Junmin, Lee, KangJu, Kim, Dae-Duk, Cho, Hyun-Jong
Format: Article
Language:English
Subjects:
Animals
Catechol
Crosslinking
Donepezil - chemistry
Donepezil - pharmacology
Dopamine - chemistry
Dopamine - pharmacology
Drug Delivery Systems
Humans
Hyaluronic acid
Hyaluronic Acid - chemistry
Hyaluronic Acid - pharmacology
Hydrogel
Hydrogels - chemistry
Hydrogels - pharmacology
Hydrogen-Ion Concentration
Injections, Subcutaneous
Mice
Microspheres
Optical Imaging
Phosphates - chemistry
Polylactic Acid-Polyglycolic Acid Copolymer - chemistry
Polylactic Acid-Polyglycolic Acid Copolymer - pharmacology
Potassium Compounds - chemistry
Potassium phosphate
Rheology
Solubility
Viscoelastic Substances - chemistry
Viscoelastic Substances - pharmacology
Water - chemistry
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Summary:Monopotassium phosphate and pH modulation-reinforced hydrogel based on hyaluronic acid (HA) grafted with dopamine (dopa) was fabricated as one of subcutaneous injection formulations of donepezil (DPZ). Both incorporation of KH2PO4 and pH adjustment finally attributed to tuning viscoelastic and biodegradable properties of hydrogel system. Appropriate gelation time for in situ gel formation, single syringe injectability, self-healing capability, and viscoelastic features were accomplished with the optimization of KH2PO4 concentration in hydrogel systems. DPZ base (as a poorly water soluble drug) was encapsulated in poly(lactic-co-glycolic acid) (PLGA) microsphere (MS) and it was further embedded in the hydrogel structure for sustained drug release. Biodegradability of designed KH2PO4-incorporated HA-dopa/DPZ MS hydrogel system was assessed by optical imaging and the remained gel weight of crosslinked HA-dopa hydrogel group was 3.4-fold higher than that of unmodified HA-dopa mixture group on day 14 (p 
ISSN:0141-8130
1879-0003
DOI:10.1016/j.ijbiomac.2020.09.089