Department of Biochemistry, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.
J Liposome Res. 2013 Mar;23(1):54-60. doi: 10.3109/08982104.2012.742536. Epub 2012 Dec 17.
The aim of the present study was to characterize a liposome-based benzocaine (BZC) formulation designed for topical use on the oral mucosa and to evaluate its in vitro retention and permeation using the Franz-type diffusion cells through pig esophagus mucosa. To predict the effectiveness of new designed formulations during preclinical studies, a correlation between in vitro assays and in vivo efficacy was performed. Liposomal BZC was characterized in terms of membrane/water partition coefficient, encapsulation efficiency, size, polydispersity, zeta potential, and morphology. Liposomal BZC (BL10) was incorporated into gel formulation and its performances were compared to plain BZC gel (B10) and the commercially available BZC gel (B20). BL10 and B10 presented higher flux and retention on pig esophagus mucosa with a shorter lag time, when compared to B20. BZC flux was strongly correlated with in vivo anesthetic efficacy, but not with topical anesthesia duration. The retention studies did not correlate with any of the in vivo efficacy parameters. Thus, in vitro permeation study can be useful to predict anesthetic efficacy during preclinical tests, because a correlation between flux and anesthetic efficacy was observed. Therefore, in vitro assays, followed by in vivo efficacy, are necessary to confirm anesthetic performance.
本研究旨在对一种基于脂质体的苯佐卡因（BZC）配方进行表征，该配方旨在用于口腔黏膜的局部应用，并使用 Franz 型扩散池通过猪食管黏膜评估其体外保留和渗透性能。为了在临床前研究中预测新设计配方的有效性，进行了体外测定与体内疗效之间的相关性研究。从膜/水分配系数、包封效率、大小、多分散性、Zeta 电位和形态等方面对脂质体 BZC 进行了表征。将脂质体 BZC（BL10）掺入凝胶制剂中，并将其性能与普通 BZC 凝胶（B10）和市售 BZC 凝胶（B20）进行了比较。与 B20 相比，BL10 和 B10 在猪食管黏膜上具有更高的通量和保留率，且滞后时间更短。BZC 通量与体内麻醉效果呈强相关性，但与局部麻醉持续时间无关。保留研究与任何体内疗效参数均无相关性。因此，体外渗透研究可用于预测临床前试验中的麻醉效果，因为观察到通量与麻醉效果之间存在相关性。因此，有必要进行体外测定和体内疗效研究，以确认麻醉性能。
