Corium International, Inc., 235 Constitution Drive, Menlo Park, California 94025, USA.
Pharm Res. 2011 Jan;28(1):22-30. doi: 10.1007/s11095-010-0174-y. Epub 2010 Jun 10.
The purpose of this work is to demonstrate the feasibility of using a proprietary technology called MicroCor™, based on solid-state, biodegradable microstructures (SSBMS), for transdermal delivery of macromolecules.
The proteins FITC-BSA (66 kDa) and recombinant protective antigen (rPA; 83 kDa) were incorporated into SSBMS arrays using a mold-based, liquid formulation casting and drying process. Arrays were applied to the skin with a custom applicator and then inspected to assess the extent of microstructure dissolution. In vitro FITC-BSA delivery to human cadaver skin was visualized using light and fluorescence microscopy and quantified by extracting and measuring the fluorescently labeled protein. rPA-containing SSBMS arrays were applied in vivo to Sprague-Dawley rats. The resulting serum IgG response was measured by ELISA and compared with responses elicited from intramuscular (IM) and intradermal (ID) routes of administration.
FITC-BSA and rPA SSBMS arrays successfully penetrated the skin. Microstructure dissolution was observed over >95% of the array area and >75% of the microstructure length. FITC-BSA delivery correlated with protein content in the formulations. Antibody titers after transdermal delivery of rPA were comparable or higher than IM and ID titers.
Transdermal delivery of macromolecules can be conveniently and effectively accomplished using the MicroCor technology.
本研究旨在展示一种名为 MicroCor™的专有技术的可行性，该技术基于固态可生物降解微结构（SSBMS），用于大分子的经皮给药。
将 FITC-BSA（66 kDa）和重组保护性抗原（rPA；83 kDa）两种蛋白质采用模具为基础的液态配方浇铸和干燥工艺纳入 SSBMS 阵列中。采用定制的敷贴器将阵列应用于皮肤，然后检查以评估微结构溶解的程度。采用荧光显微镜和提取并测量荧光标记的蛋白质来可视化和定量人尸体皮肤中的 FITC-BSA 体外递送。将含有 rPA 的 SSBMS 阵列应用于 Sprague-Dawley 大鼠的体内。通过 ELISA 测量产生的血清 IgG 反应，并与肌肉内（IM）和皮内（ID）给药途径引起的反应进行比较。
FITC-BSA 和 rPA SSBMS 阵列成功穿透皮肤。观察到超过 95%的阵列区域和超过 75%的微结构长度的微结构溶解。FITC-BSA 递送与制剂中的蛋白质含量相关。rPA 经皮给药后的抗体滴度与 IM 和 ID 滴度相当或更高。
使用 MicroCor 技术可方便有效地实现大分子的经皮给药。
