Transdermal absorption and stability enhancement of salmon calcitonin by Tat peptide
Transdermal absorption and stability enhancement of salmon calcitonin by Tat peptide
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DOI：
10.3109/03639045.2012.684388
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发表时间：
2013-04-01
影响因子：
3.4
通讯作者：
Manosroi, Aranya
中科院分区：
文献类型：
--
作者：
Manosroi, Jiradej;Lohcharoenkal, Warangkana;Manosroi, Aranya
背景：角质层的高度组织化结构是蛋白质和多肽等大分子物质通过皮肤传递的主要障碍。最近，细胞穿透肽(CPPs)，如HIV1反式激活转录(TAT)，已被用于增强蛋白质和多肽的局部递送。目的：研究三文鱼降钙素(SCT)与TAT共孵育后的透皮吸收及化学稳定性。材料和方法：制备摩尔比为1：1的TAT-SCT混合物。以游离SCT为对照，考察了该制剂的透皮吸收和化学稳定性。结果：TAT-SCT混合物的SCT累积释放量和释药通量均高于游离SCT。在TAT-SCT混合物中，6h时SCT透过率最大，为58.36+/-12.33%，是游离SCT的3.50倍。TAT-SCT混合物在4℃、25℃和45℃保存1个月后，SCT的稳定性优于SCT溶液。讨论：TAT中的正电荷精氨酸基团可能与多肽复合物通过静电相互作用结合到带负电荷的细胞表面有关，也可能是SCT通过离体皮移位的原因。结论：TAT多肽具有促进SCT透皮吸收和稳定性的作用，可进一步应用于其他治疗性多肽的透皮吸收。
Context: 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. Objective: This study aimed to enhance the transdermal absorption and chemical stability of salmon calcitonin (sCT) by co-incubation with Tat. Materials and methods: 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. Results: 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 degrees C and 45 degrees C. Discussion: 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. Conclusion: 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.