Bioengineering Department, Instituto Superior Técnico, University of Lisbon, Institute for Bioengineering and Biosciences, Lisbon, Portugal.
Associate Laboratory, i4HB-Institute for Health and Bioeconomy at Instituto Superior Técnico, University of Lisbon, Brisbane, Australia.
Adv Exp Med Biol. 2022;1357:43-82. doi: 10.1007/978-3-030-88071-2_3.
The extensive knowledge in the miniemulsion technique used in biocatalysis applications by the authors allowed the development of drug delivery systems that constitutes the LipNanoCar technology core for the production of lipid nanoemulsions and solid lipid nanoparticles. The LipNanoCar technology, together with adequate formulations of different oils, fatty acids, surfactants, and temperature, allows the entrapment of several bioactive and therapeutic compounds in lipid nanoparticles for cosmetic, nutrition, and pharmaceutical applications.The LIpNanoCar technology allowed lipid nanoparticles production with average sizes ranging from 100 to 300 nm and Zeta Potentials between -55 and -20 mV. Concomitantly, high entrapment or encapsulation efficiencies (%EE) were achieved, as illustrated in this work for β-carotene and vitamins derivatives (>85%) for cosmetic application, and for antibiotics currently used in chemotherapy, like rifampicin (69-85%) and pyrazinamide (14-29%) against Mycobacterium tuberculosis (TB), and ciprofloxacin (>65%) and tobramycin (~100%) in Cystic Fibrosis (CF) respiratory infections therapy. Ciprofloxacin presented, for example, a quick-release from the lipid nanoparticles using a dialysis tubing (96% in the first 7 h), but slower than the free antibiotic (95% in the first 3 h). This result suggests that ciprofloxacin is loaded near the external surface of the lipid nanoparticles.The toxicity and validation of entrapment of antibiotics in lipid nanoparticles for Cystic Fibrosis therapy were assessed using Caenorhabditis elegans as an animal model of bacterial infection. Fluorescence microscopy of an entrapped fluorescent dye (DiOC) confirmed the uptake of the lipid nanoparticles by ingestion, and their efficacy was successfully tested in C. elegans. Burkholderia contaminans IST408 and Burkholderia cenocepacia K56-2 infections were tested as model bacterial pathogens difficult to eradicate in Cystic Fibrosis respiratory diseases.
作者在生物催化应用的细乳液技术方面拥有广泛的知识，这使得他们能够开发出药物输送系统，该系统构成了 LipNanoCar 技术的核心，用于生产脂质纳米乳液和固体脂质纳米粒。LipNanoCar 技术与不同油、脂肪酸、表面活性剂和温度的适当配方相结合，允许将几种生物活性和治疗化合物包封在脂质纳米粒中，用于美容、营养和制药应用。LipNanoCar 技术允许生产平均粒径为 100 至 300nm 且 Zeta 电位在-55 至-20mV 之间的脂质纳米粒。同时，如这项工作所示，实现了高包封或包封效率（%EE），对于美容应用的β-胡萝卜素和维生素衍生物（>85%），以及目前用于化疗的抗生素，如利福平（69-85%）和吡嗪酰胺（14-29%）抗结核分枝杆菌（TB），以及环丙沙星（>65%）和妥布霉素（~100%）在囊性纤维化（CF）呼吸道感染治疗中。例如，使用透析管可使脂质纳米粒中的环丙沙星迅速释放（前 7 小时内 96%），但比游离抗生素慢（前 3 小时内 95%）。这一结果表明，环丙沙星被加载到脂质纳米粒的外表面附近。使用秀丽隐杆线虫作为细菌感染的动物模型，评估了脂质纳米粒中抗生素包封的毒性和验证用于囊性纤维化治疗。包封荧光染料（DiOC）的荧光显微镜证实了脂质纳米粒通过摄取被吸收，并且它们在秀丽隐杆线虫中的功效已成功测试。Burkholderia contaminans IST408 和 Burkholderia cenocepacia K56-2 感染被用作囊性纤维化呼吸道疾病中难以根除的模型细菌病原体进行测试。
