School of Pharmacy, Yanbian University, Yanji, 133002, China.
Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, China.
AAPS PharmSciTech. 2022 Jul 19;23(6):199. doi: 10.1208/s12249-022-02362-1.
Griseofulvin (GF) is used as an antifungal to treat superficial skin fungal infections such as tinea capitis and tinea pedis. Currently, GF is only available in traditional oral dosage forms and suffers from poor and highly variable bioavailability, hepatotoxicity, and long duration of treatment. Therefore, the main objective of this study was to reduce the side effects of the drug and to increase the concentration of the drug retained in the cutaneous stratum corneum (SC) and improve its efficacy through the preparation of drug-laden GF microsponge (GFMS). The emulsification-solvent-diffusion method was used to prepare GFMS, and the prescriptions were screened by a single-factor approach. The optimized formulation (GFF8) had a microsponge particle size (μm) of 28.36 ± 0.26, an encapsulation efficiency (%) of 87.53 ± 1.07, a yield (%) of 86.58 ± 0.42, and drug release (%) from 77.57 ± 3.88. The optimized microsponge formulation was then loaded into a Carbopol 934 gel matrix and skin retention differences between the microsponge gel formulation and normal gels were examined by performing skin retention and fluorescence microscopy tests. Finally, the hepatoprotective and cutaneous stratum corneum retention abilities of microsponge gel formulations compared to oral GF formulations were assessed by hepatotoxicity, pharmacokinetics, and tissue distribution studies. This provides a new perspective on GF dermal stratum corneum retention administration.
灰黄霉素(GF)被用作抗真菌药物,用于治疗头癣和足癣等浅表皮肤真菌感染。目前,GF 仅可通过传统口服剂型获得,其生物利用度差且变异性大、具有肝毒性,且治疗时间长。因此,本研究的主要目的是通过制备载药灰黄霉素微球(GFMS)来降低药物的副作用,增加药物在皮肤角质层(SC)中的保留浓度,并提高其疗效。采用乳化-溶剂扩散法制备 GFMS,并通过单因素法筛选处方。优化处方(GFF8)的微球粒径(μm)为 28.36±0.26,包封率(%)为 87.53±1.07,产率(%)为 86.58±0.42,药物释放率(%)为 77.57±3.88。然后将优化的微球配方载入卡波姆 934 凝胶基质中,并通过皮肤滞留和荧光显微镜试验,考察微球凝胶制剂与普通凝胶制剂的皮肤滞留差异。最后,通过肝毒性、药代动力学和组织分布研究,评估微球凝胶制剂与口服 GF 制剂相比的肝保护和皮肤角质层滞留能力。这为 GF 经皮角质层给药提供了新的视角。