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.
Orobol is an isoflavone that has a potent skin protection effect. The objective of this study was to prepare a novel bentonitebased composite formulation of orobol to enhance topical skin delivery. Methods: The composition was optimized based on the orobol content in the composite and the in vitro release studies, followed by the in vitro and in vivo hairless mouse skin deposition studies. Physicochemical characterizations of the composite formulation were performed by powder X-ray refractometry (XRD) and scanning electron microscopy (SEM). The in vitro cytotoxicity and in vivo toxicity studies were conducted in human keratinocytes and in hairless mouse, respectively.
Results and Discussions:The in vitro release of orobol from the bentonite composites was higher than that from the suspension, which was further increased with the addition of phosphatidylcholine. The composite formulation significantly enhanced the in vitro and in vivo skin deposition of orobol in hairless mouse skin compared to the orobol suspension. Moreover, the addition of phosphatidyl choline not only improved the dissolution and incomplete release of orobol from the bentonite composite but also enhanced the deposition of orobol in the skin. XRD histograms and SEM images confirmed that the enhanced dissolution of orobol from the composite was attributed to its amorphous state on bentonite. The in vitro and in vivo toxicity studies support the safety and biocompatibility of the orobol-loaded bentonite composite formulation. Conclusion: These findings suggest that the orobol-loaded bentonite composite formulation could be a potential topical skin delivery system for orobol.
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