Department of Pharmaceutical Sciences, University of Florence, Italy.
J Liposome Res. 2009;19(4):253-60. doi: 10.3109/08982100902788408.
This study aimed to investigate the influence of the preparation conditions on the performance of an ethosomal formulation for topical delivery of the local anesthetic agent, benzocaine (BZC). Ethosomes were prepared with different techniques, such as thin-layer evaporation, freezing and thawing, reverse-phase evaporation, extrusion and sonication, obtaining, respectively, multilayer vesicles (MLVs), frozen and thawed MLV (FATMLV), large unilamellar vesicles (LUVs), and small unilamellar vesicles (SUVs). The obtained vesicles were characterized for morphology, size, zeta potential, and entrapment efficiency (EE%), and their stability was monitored during storage at 4 degrees C. In vitro permeation properties from gels incorporating drug ethosomal dispersions were evaluated in vitro by using artificial lipophilic membranes, while their anesthetic effect was determined in vivo on rabbits. The results suggested that the vesicle preparation method plays an important role in affecting the properties and effectiveness of ethosomal formulations. MLVs and LUVs exhibited higher drug EE% and better stability than FATMLV and SUV vesicles. The In vitro drug permeation rate was directly related to the vesicle EE% and varied in the order MLV>LUV approximately FATMLV>SUV. The therapeutic efficacy of BZC ethosomal formulations was significantly improved with respect to the corresponding BZC solution. The best results, in terms of enhanced intensity of anesthetic effect, were given by formulations containing MLVs and LUVs, and the order of effectiveness was MLV approximately LUV>FATMLV approximately SUV, rather similar to that found in permeation studies. On the contrary, unexpectedly, the effectiveness order in increasing the duration of drug action was SUV> or =MLV>LUV approximately FATMLV. The highest efficacy of SUVs was probably due to the more intimate contact with the epithelium due to their greatest surface area, which allowed the longest extension of drug therapeutic action. The overall results suggest that a suitably developed ethosomal formulation of BZC can be of actual value for improving its clinical effectiveness in topical anesthesia.
本研究旨在探讨不同制备条件对局部麻醉剂苯佐卡因（BZC）经皮传递的醇质体制剂性能的影响。采用薄膜蒸发法、冻融法、反相蒸发法、挤出法和超声法分别制备多层囊泡（MLVs）、冻融 MLV（FATMLV）、大单层囊泡（LUVs）和小单层囊泡（SUVs）。对所得囊泡进行形态、粒径、Zeta 电位和包封率（EE%）的表征，并在 4°C 下储存过程中监测其稳定性。通过使用人工亲脂性膜评估含药物醇质体分散体的凝胶的体外渗透特性，同时在兔体内测定其麻醉效果。结果表明，囊泡制备方法对醇质体制剂的性质和效果有重要影响。MLVs 和 LUVs 表现出更高的药物 EE%和更好的稳定性，而 FATMLV 和 SUV 囊泡则较差。体外药物渗透速率与囊泡 EE%直接相关，其变化顺序为 MLV>LUV>≈FATMLV>SUV。与相应的 BZC 溶液相比，BZC 醇质体制剂的治疗效果显著提高。就增强麻醉效果的强度而言，MLVs 和 LUVs 所含的制剂效果最好，其有效性顺序为 MLV≈LUV>FATMLV≈SUV，与渗透研究结果相似。相反，出乎意料的是，延长药物作用时间的有效性顺序为 SUV≥MLV>LUV≈FATMLV。SUV 之所以具有较高的疗效，可能是由于其表面积最大，与上皮细胞的接触更为密切，从而使药物的治疗作用得以最长时间的延长。总的来说，研究结果表明，适当开发的 BZC 醇质体制剂可以实际提高其在局部麻醉中的临床效果。
