Biochemistry and Tissue Biology Department, Institute of Biology , University of Campinas (UNICAMP) , 13083-862 Campinas , São Paulo , Brazil.
Pharmacy Department , UNINASSAU College , 59080-400 Natal , Rio Grande do Norte , Brazil.
Langmuir. 2018 Nov 6;34(44):13296-13304. doi: 10.1021/acs.langmuir.8b02559. Epub 2018 Oct 24.
Dibucaine (DBC) is one of the most potent long-acting local anesthetics, but it also has significant toxic side effects and low water solubility. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been proposed as drug-delivery systems to increase the bioavailability of local anesthetics. The purpose of the present study was to characterize SLNs and NLCs composed of cetyl palmitate or myristyl myristate, a mixture of capric and caprylic acids (for NLCs only) plus Pluronic F68 prepared for the encapsulation of DBC. We intended to provide a careful structural characterization of the nanoparticles to identify the relevant architectural parameters that lead to the desirable biological response. Initially, SLNs and NLCs were assessed in terms of their size distribution, morphology, surface charge, and drug loading. Spectroscopic techniques (infrared spectroscopy and electron paramagnetic resonance, EPR) plus small-angle X-ray scattering (SAXS) provided information on the interactions between nanoparticle components and their structural organization. The sizes of nanoparticles were in the 180 nm range with low polydispersity and negative zeta values (-25 to -46 mV). The partition coefficient of DBC between nanoparticles and water at pH 8.2 was very high (>10). EPR (with doxyl-stearate spin labels) data revealed the existence of lamellar arrangements inside the lipid nanoparticles, which was also confirmed by SAXS experiments. Moreover, the addition of DBC increased the molecular packing of both SLN and NLC lipids, indicative of DBC insertion between the lipids, in the milieu assessed by spin labels. Such structural information brings insights into understanding the molecular organization of these versatile drug-delivery systems which have already demonstrated their potential for therapeutic applications in pain control.
地布卡因（DBC）是一种作用时间最长、效力最强的局部麻醉剂，但它也具有显著的毒性副作用和低水溶性。固体脂质纳米粒（SLN）和纳米结构脂质载体（NLC）已被提议作为药物递送系统，以提高局部麻醉剂的生物利用度。本研究的目的是对由十六烷酸棕榈酯或十四烷酸肉豆蔻酯、辛酸和癸酸的混合物（仅用于 NLC）以及泊洛沙姆 F68 组成的 SLN 和 NLC 进行表征，以包封 DBC。我们旨在对纳米粒进行仔细的结构表征，以确定导致理想生物学反应的相关结构参数。最初，根据粒径分布、形态、表面电荷和载药量对 SLN 和 NLC 进行了评估。光谱技术（红外光谱和电子顺磁共振，EPR）加上小角 X 射线散射（SAXS）提供了关于纳米粒子成分之间相互作用及其结构组织的信息。纳米粒子的粒径在 180nm 范围内，具有低多分散性和负的 Zeta 值（-25 至-46mV）。在 pH8.2 时，DBC 在纳米粒子与水之间的分配系数非常高（>10）。EPR（用二氢胆甾醇自旋标记）数据显示了在脂质纳米粒内存在层状排列，这也通过 SAXS 实验得到了证实。此外，DBC 的加入增加了 SLN 和 NLC 脂质的分子堆积，这表明在评估的环境中，DBC 插入了脂质之间。这种结构信息使我们深入了解这些多功能药物递送系统的分子组织，这些系统已经证明了它们在疼痛控制治疗应用中的潜力。
