Combined Orobol-Bentonite Composite Formulation for Effective Topical Skin Targeted Therapy in Mouse Model

Duy-Thuc Nguyen,1 Min-Hwan Kim,1 Na-Young Yu,1 Min-Jun Baek,1 Kyung-Sun Kang,2 Ki Won Lee,3 Dae-Duk Kim1 1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; 2Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea; 3Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of KoreaCorrespondence: Dae-Duk Kim, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea, Tel +82-2-880-7870, Fax +82-2-873-9177, Email ddkim@snu.ac.krPurpose: Orobol is an isoflavone that has a potent skin protection effect. The objective of this study was to prepare a novel bentonite-based 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.Keywords: orobol, bentonite, composite, phosphatidylcholine, skin, topical delivery