纳米结构脂质载体(NLC)已成为创新的药物递送系统,与其他基于脂质的载体相比,具有明显的优势,如脂质体和固体脂质纳米颗粒。苯佐卡因(BZC),使用中最古老的局部麻醉剂,通过假胆碱酯酶进行代谢,导致对氨基苯甲酸的形成,与长期使用BZC相关的过敏反应的病原体。为了减轻不良反应和提高生物利用度,BZC封装在NLC内。利用23阶乘设计,包含棕榈酸鲸蜡酯(固体脂质)的制剂,丙二醇单辛酸酯(液体脂质),并系统地制备了以PluronicF68为表面活性剂,随着固体/液体脂质质量比(60:40-80:20%)的变化,总脂质含量(15-25%),和BZC浓度(1-3%)。通过动态光散射对优化的配方进行表征,差示扫描量热法,拉曼成像,X射线衍射,小角度中子散射,纳米裂纹分析,透射电子显微镜(TEM)/低温TEM,提供对纳米颗粒结构和BZC掺入其脂质基质的见解。NLCBZC表现出显著的包封效率(%EE=96%)和在25°C下储存时的1年稳定性。在小鼠中进行的体外动力学研究和体内镇痛试验表明,NLCBZC有效地持续药物释放超过20小时,并将BZC的麻醉效果延长至18小时。因此,我们建议使用NLCBZC来减少苯佐卡因的有效麻醉浓度(从20到3%或更低),从而最大程度地减少局部施用这种麻醉剂后的过敏反应,潜在的,为疼痛管理中BZC给药的新途径铺平了道路。
Nanostructured lipid carriers (NLC) have emerged as innovative drug delivery systems, offering distinct advantages over other lipid-based carriers, such as liposomes and solid lipid nanoparticles. Benzocaine (BZC), the oldest topical local anesthetic in use, undergoes metabolism by pseudocholinesterase, leading to the formation of p-aminobenzoic acid, a causative agent for allergic reactions associated with prolonged BZC usage. In order to mitigate adverse effects and enhance bioavailability, BZC was encapsulated within NLC. Utilizing a 23 factorial design, formulations comprising cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid), and Pluronic F68 as surfactants were systematically prepared, with variations in the solid/liquid lipid mass ratios (60:40-80:20%), total lipid contents (15-25%), and BZC concentrations (1-3%). The optimized formulation underwent characterization by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis, and transmission electron microscopy (TEM)/cryo-TEM, providing insights into the nanoparticle structure and the incorporation of BZC into its lipid matrix. NLCBZC exhibited a noteworthy encapsulation efficiency (%EE = 96%) and a 1 year stability when stored at 25 °C. In vitro kinetic studies and in vivo antinociceptive tests conducted in mice revealed that NLCBZC effectively sustained drug release for over 20 h and prolonged the anesthetic effect of BZC for up to 18 h. We therefore propose the use of NLCBZC to diminish the effective anesthetic concentration of benzocaine (from 20 to 3% or less), thus minimizing allergic reactions that follow the topical administration of this anesthetic and, potentially, paving the way for new routes of BZC administration in pain management.