Lopes Luciana B, Ferreira Denise A, de Paula Daniel, Garcia M Tereza J, Thomazini José A, Fantini Márcia C A, Bentley M Vitória L B
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/n, Ribeirão Preto, SP 14040-903, Brazil.
Pharm Res. 2006 Jun;23(6):1332-42. doi: 10.1007/s11095-006-0143-7. Epub 2006 May 25.
To obtain and characterize reverse hexagonal phase nanodispersions of monoolein and oleic acid, and to evaluate the ability of such system to improve the skin penetration of a model peptide (cyclosporin A, CysA) without causing skin irritation.
The nanodispersion was prepared by mixing monoolein, oleic acid, poloxamer, and water. CysA was added to the lipid mixture to obtain a final concentration of 0.6% (w/w). The nanodispersion was characterized; the skin penetration of CysA was assessed in vitro (using porcine ear skin mounted in a Franz diffusion cell) and in vivo (using hairless mice).
The obtainment of the hexagonal phase nanodispersion was demonstrated by polarized light microscopy, cryo-TEM and small angle X-ray diffraction. Particle diameter was 181.77 +/- 1.08 nm. At 0.6%, CysA did not change the liquid crystalline structure of the particles. The nanodispersion promoted the skin penetration of CysA both in vitro and in vivo. In vitro, the maximal concentrations (after 12 h) of CysA obtained in the stratum corneum (SC) and in the epidermis without stratum corneum (E) + dermis (D) were approximately 2 fold higher when CysA was incorporated in the nanodispersion than when it was incorporated in the control formulation (olive oil). In vivo, 1.5- and 2.8-times higher concentrations were achieved in the SC and [E+D], respectively, when the nanodispersion was employed. No histopathological alterations were observed in the skin of animals treated with the nanodispersion.
These results demonstrate that the hexagonal phase nanodispersion is effective in improving the topical delivery of peptides without causing skin irritation.
制备并表征单油酸甘油酯和油酸的反相六角相纳米分散体，并评估该体系在不引起皮肤刺激的情况下改善模型肽（环孢素A，CysA）皮肤渗透的能力。
通过混合单油酸甘油酯、油酸、泊洛沙姆和水来制备纳米分散体。将CysA添加到脂质混合物中，使其终浓度达到0.6%（w/w）。对纳米分散体进行表征；在体外（使用安装在Franz扩散池中的猪耳皮肤）和体内（使用无毛小鼠）评估CysA的皮肤渗透性。
通过偏光显微镜、冷冻透射电子显微镜和小角X射线衍射证实了六角相纳米分散体的形成。粒径为181.77±1.08nm。在0.6%的浓度下，CysA不会改变颗粒的液晶结构。该纳米分散体在体外和体内均促进了CysA的皮肤渗透。在体外，当CysA被掺入纳米分散体中时，角质层（SC）以及无角质层的表皮（E）+真皮（D）中获得的CysA最大浓度（12小时后）比其被掺入对照制剂（橄榄油）时高约2倍。在体内，当使用纳米分散体时，SC和[E+D]中的浓度分别提高了1.5倍和2.8倍。在用纳米分散体处理的动物皮肤中未观察到组织病理学改变。
这些结果表明，六角相纳米分散体在改善肽的局部递送方面有效，且不会引起皮肤刺激。
