Basha Mona, Abd El-Alim Sameh Hosam, Kassem Ahmed Alaa, El Awdan Sally, Awad Gamal
Pharmaceutical Technology Department, National Research Centre, Cairo, 12622 Egypt.
Curr Drug Deliv. 2015;12(6):680-92. doi: 10.2174/1567201812666150703115126.
The aim of the present work is the development and evaluation of solid lipid nanoparticles (SLNs) as carrier system for topical delivery of benzocaine (BZC) improving its local anesthesia aiming to produce a fast acting and long lasting topical formulation. BZC loaded SLNs were prepared using a full factorial design to study the influence of the type of polyoxyethylene sorbitan ester surfactants as well as their concentration as independent variables on the particle size, entrapment efficacy and zeta potential selected as dependent variables. Design of experiment (DOE) and the analysis of variance (ANOVA) were conducted to assess the optimization of the developed formulations. The results indicated that the fatty acid chain length of tested surfactants and their concentration had a significant effect on the studied responses. The optimized formulations were spherical in shape of mean particle diameters<350 nm with negatively charged surface <-20mV. Particles were characterized using differential scanning calorimetry and X-ray powder diffraction confirming the amorphous nature and the uniformity of drug inclusion in the lipid matrix. Optimized BZC-SLNs were incorporated into hydrogels characterized by a pseudoplastic non-Newtonian behavior. In vitro release study revealed an apparently biphasic release process with sustained release profile following Higuchi kinetics. BZC loaded SLNs hydrogels showed more potent anesthetic effect compared to BZC hydrogel evaluated using tail-flick analgesimeter, confirming significant improvement in both the intensity and duration of anesthetic effect. The above results proved that SLNs represent good candidates to encapsulate BZC improving its therapeutic efficacy for the topical treatment of pain.
本研究的目的是开发和评估固体脂质纳米粒（SLNs）作为苯佐卡因（BZC）局部给药的载体系统，以改善其局部麻醉效果，旨在制备一种起效快且持久的局部制剂。采用全因子设计制备了负载BZC的SLNs，以研究聚氧乙烯山梨糖醇酯表面活性剂的类型及其浓度作为自变量对粒径、包封率和zeta电位（作为因变量）的影响。进行了实验设计（DOE）和方差分析（ANOVA）以评估所开发制剂的优化情况。结果表明，测试表面活性剂的脂肪酸链长度及其浓度对所研究的响应有显著影响。优化后的制剂呈球形，平均粒径<350 nm，表面带负电荷<-20 mV。使用差示扫描量热法和X射线粉末衍射对颗粒进行表征，证实了脂质基质中药物包封的无定形性质和均匀性。将优化后的BZC-SLNs掺入具有假塑性非牛顿行为特征的水凝胶中。体外释放研究显示出明显的双相释放过程，遵循Higuchi动力学的缓释曲线。与使用甩尾镇痛仪评估的BZC水凝胶相比，负载BZC的SLNs水凝胶显示出更强的麻醉效果，证实了麻醉效果在强度和持续时间上均有显著改善。上述结果证明，SLNs是包封BZC的良好候选物，可提高其在局部疼痛治疗中的疗效。
