Subcutaneously Injectable Hyaluronic Acid Hydrogel for Sustained Release of Donepezil with Reduced Initial Burst Release: Effect of Hybridization of Microstructured Lipid Carriers and Albumin

Pharmaceutics

Ju-Hwan Park¹  Na-Young Yu¹  Dae-Duk Kim¹  So-Yeon Yoon¹  Nae-Won Kang¹  Sungho Kim¹  Jae-Young Lee²  Hyun-Jong Cho³ 

[1] College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea;College of Pharmacy, Chungnam National University, Daejeon 34134, Korea;College of Pharmacy, Kangwon National University, Chuncheon 24341, Korea;

关键词: hyaluronic acid;    hydrogel;    microstructured lipid carrier;    human serum albumin;    sustained release;    reduced initial burst release;   

DOI  :  10.3390/pharmaceutics13060864

来源: DOAJ

【 摘 要 】

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 C_max value was 0.3-fold lower than that of the control hydrogel without a significant change in the AUC_last 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.

【 授权许可】

Unknown