Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
Drug Dev Ind Pharm. 2013 Apr;39(4):520-5. doi: 10.3109/03639045.2012.684388. Epub 2012 May 8.
Highly organized structure of stratum corneum (SC) is the major barrier of the delivery of macromolecules such as proteins and peptides across the skin. Recently, cell penetrating peptides (CPPs) such as HIV1-trans-activating transcriptional (Tat) have been used to enhance the topical delivery of proteins and peptides.
This study aimed to enhance the transdermal absorption and chemical stability of salmon calcitonin (sCT) by co-incubation with Tat.
Tat-sCT mixture at 1:1 molar ratio was prepared. Transdermal absorption and chemical stability of the mixture was evaluated in comparing with free sCT.
Tat-sCT mixture gave higher cumulative amounts and fluxes of sCT than free sCT. The maximum percentage of sCT of 58.36 ± 12.33% permeated into the receiving chamber was found in Tat-sCT mixture at 6 h which was 3.50 folds of free sCT. Tat-sCT mixture demonstrated better sCT stability than sCT solution after 1 month storage at 4°C, 25°C and 45°C.
The positively-charged arginine groups in Tat might be responsible for the binding of peptide complexes to negatively charged cell surfaces by electrostatic interactions and also the translocation of sCT through the excised skin.
This study demonstrated the enhancements of transdermal absorption and stability of sCT by Tat peptide with potential for further application in transdermal delivery of other therapeutic peptides.
高度有序的角质层（SC）结构是蛋白质和肽等大分子穿越皮肤的主要屏障。最近，细胞穿透肽（CPP）如 HIV1-转录激活转录（Tat）已被用于增强蛋白质和肽的局部递送。
本研究旨在通过与 Tat 共孵育来增强鲑鱼降钙素（sCT）的透皮吸收和化学稳定性。
制备 Tat-sCT 摩尔比为 1:1 的混合物。通过与游离 sCT 比较，评估混合物的透皮吸收和化学稳定性。
Tat-sCT 混合物比游离 sCT 给予更高的 sCT 累积量和通量。在 6 h 时，Tat-sCT 混合物中 sCT 的最大透皮百分比为 58.36±12.33%，是游离 sCT 的 3.50 倍。Tat-sCT 混合物在 4°C、25°C 和 45°C 下储存 1 个月后，sCT 的稳定性优于 sCT 溶液。
Tat 中的正电荷精氨酸可能负责通过静电相互作用将肽复合物与带负电荷的细胞表面结合，并且 sCT 通过离体皮肤的转位。
本研究证明了 Tat 肽增强了 sCT 的透皮吸收和稳定性，具有进一步应用于其他治疗性肽的透皮递送的潜力。
