São Paulo State University (UNESP), Department of Physics and Chemistry, School of Engineering, Ilha Solteira, SP, Brazil.
Human and Natural Sciences Center, Federal University of ABC (UFABC), Santo André, SP, Brazil.
Colloids Surf B Biointerfaces. 2019 Feb 1;174:56-62. doi: 10.1016/j.colsurfb.2018.10.063. Epub 2018 Oct 26.
In recent years, the development of hybrid drug delivery systems, such as hydrogels and nanoparticles, has gained considerable attention as new formulations for skin-delivery. Meanwhile, transdermal diffusion synthetic membranes have been used to assess skin permeability to these systems, providing key insights into the relationships between drug and nanoformulations. In this study, benzocaine-loaded poly-ε-caprolactone nanoparticles (BZC:NPs) were synthesized, characterized and incorporated into Poloxamer 407-based hydrogel (PL407). Benzocaine (BZC) was used as a drug model since has been commonly applied as a topical pain reliever in the last years. Hence, we developed a hybrid polymeric nanoparticle/thermosensitive hydrogels system and evaluated the in vitro permeation of the BZC, as well as nanoformulation tracking in an artificial membrane. In vitro permeation study was conducted in a vertical diffusion cell system using a Strat-M membrane model. BZC:NPs were prepared by coprecipitation method and their physicochemical stability measured before incorporating into the thermosensitive hydrogel. Also, viscosity measurements and sol-gel transition temperature were performed by rheological analysis. Different techniques, including microscopy, were used to tracking the nanoparticles on both receptor medium and synthetic membranes. Results showed high BZC encapsulation efficiency into NPs (93%) and good physicochemical stability before and after hydrogel incorporation. BZC in vitro permeation kinetics from NPs-loaded Poloxamer 407-based hydrogel presented slower permeation profile compared with the BZC: Poloxamer 407-based hydrogel. Also, NPs were observed into the diffusion cells receptor compartment after the in vitro permeation study. These results contribute to a better understanding the interaction between hydrogels, nanoparticles and synthetic membrane, as well as open perspectives for the development of new drug delivery systems for skin.
近年来，混合药物输送系统（如水凝胶和纳米粒子）的发展受到了相当大的关注，成为皮肤输送的新配方。同时，透皮扩散合成膜已被用于评估这些系统对皮肤的渗透性，为药物和纳米制剂之间的关系提供了关键的见解。在这项研究中，合成了载有苯佐卡因的聚己内酯纳米粒子（BZC:NPs），并对其进行了表征，然后将其纳入泊洛沙姆 407 基水凝胶（PL407）中。苯佐卡因（BZC）被用作药物模型，因为近年来它已被广泛用作局部止痛药。因此，我们开发了一种混合聚合物纳米粒子/温敏水凝胶系统，并评估了 BZC 的体外渗透以及纳米制剂在人工膜中的跟踪情况。体外渗透研究在垂直扩散池系统中进行，使用 Strat-M 膜模型。BZC:NPs 通过共沉淀法制备，并在纳入温敏水凝胶之前测量其物理化学稳定性。此外，还通过流变分析进行了粘度测量和溶胶-凝胶转变温度测量。使用不同的技术，包括显微镜，来跟踪纳米粒子在受体介质和合成膜上的位置。结果表明，纳米粒子对 BZC 的包封效率高（93%），在纳入水凝胶前后物理化学稳定性良好。与 BZC:泊洛沙姆 407 基水凝胶相比，载有 BZC 的泊洛沙姆 407 基水凝胶中 BZC 的体外渗透动力学呈现出较慢的渗透曲线。此外，在体外渗透研究后，观察到纳米粒子进入扩散池受体室。这些结果有助于更好地理解水凝胶、纳米粒子和合成膜之间的相互作用，并为皮肤新药物输送系统的开发提供了新的视角。
