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

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.

Yield‐Stress and Creep Control Depot Formation and Persistence of Injectable Hydrogels Following Subcutaneous Administration

“…[ 27,28 ] Yet, after administration, the material may deform or flatten under the stresses present in the subcutaneous space ( Figure a). [ 29,30 ] This shape change has significant impact on diffusion length and corresponding release kinetics. The most common kinetic model used in drug release studies is the Ritger–Peppas model, [ 31 ] which describes drug transport through both Fickian diffusion and anomalous transport mechanisms.…”

A Comparative Evaluation of the Structural and Biomechanical Properties of Food-Grade Biopolymers as Potential Hydrogel Building Blocks

“…Furthermore, the samples were evaluated in terms of their appearance after the vials were inverted. It is a visual test to determine whether a sample has formed a gel structure or is still a sol [ 50 ].…”

Emerging Fabrication Strategies of Hydrogels and Its Applications

“…Donepezil can be released from the hydrogel in a sustained manner after subcutaneous injection. Another form of subcutaneous injection of a hyaluronic acid hydrogel was proposed by the same research group [333]. The hydrogel was hybridized with a microstructural lipid carrier and human serum albumin, which was used for the sustained release of donepezil and to reduce the initial burst release.…”