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Subcutaneously Injectable Hyaluronic Acid Hydrogel for Sustained Release of Donepezil with Reduced Initial Burst Release: Effect of Hybridization of Microstructured Lipid Carriers and Albumin
- Source :
- Pharmaceutics, Volume 13, Issue 6, Pharmaceutics, Vol 13, Iss 864, p 864 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- The daily oral administration of acetylcholinesterase (AChE) inhibitors for Alzheimer’s disease features low patient compliance and can lead to low efficacy or high toxicity owing to irregular intake. Herein, we developed a subcutaneously injectable hyaluronic acid hydrogel (MLC/HSA hydrogel) hybridized with microstructured lipid carriers (MLCs) and human serum albumin (HSA) for the sustained release of donepezil (DNP) with reduced initial burst release. The lipid carrier was designed to have a microsized mean diameter (32.6 ± 12.8 µm) to be well-localized in the hydrogel. The hybridization of MLCs and HSA enhanced the structural integrity of the HA hydrogel, as demonstrated by the measurements of storage modulus (G′), loss modulus (G″), and viscosity. In the pharmacokinetic study, subcutaneous administration of MLC/HSA hydrogel in rats prolonged the release of DNP for up to seven days and reduced the initial plasma concentration, where the Cmax value was 0.3-fold lower than that of the control hydrogel without a significant change in the AUClast value. Histological analyses of the hydrogels supported their biocompatibility for subcutaneous injection. These results suggest that a new hybrid MLC/HSA hydrogel could be promising as a subcutaneously injectable controlled drug delivery system for the treatment of Alzheimer’s disease.
- Subjects :
- Biocompatibility
reduced initial burst release
Cmax
Pharmaceutical Science
macromolecular substances
02 engineering and technology
Pharmacology
010402 general chemistry
complex mixtures
01 natural sciences
Article
chemistry.chemical_compound
Subcutaneous injection
Pharmacy and materia medica
hyaluronic acid
Hyaluronic acid
medicine
sustained release
Chemistry
technology, industry, and agriculture
Albumin
021001 nanoscience & nanotechnology
Human serum albumin
donepezil
0104 chemical sciences
RS1-441
human serum albumin
Self-healing hydrogels
Drug delivery
hydrogel
0210 nano-technology
Alzheimer’s disease
microstructured lipid carrier
medicine.drug
Subjects
Details
- ISSN :
- 19994923
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Pharmaceutics
- Accession number :
- edsair.doi.dedup.....ca8cbf3610c18b9a300ccaf4cc782f18