title: Buparvaquone Nanostructured Lipid Carrier: Development of an Affordable Delivery System for the Treatment of Leishmaniases.
abstract: Buparvaquone (BPQ), a veterinary drug, was formulated as nanostructured lipid carriers (NLC) for leishmaniases treatment. The formulation design addressed poor water solubility of BPQ and lack of human drug delivery system. The DSC/TG and microscopy methods were used for solid lipids screening. Softisan® 154 showed highest BPQ solubility in both methods. The BPQ solubility in liquid lipids using HPLC revealed Miglyol® 812 as the best option. Response surface methodology (RSM) was used to identify the optimal Softisan154 : Miglyol 812 ratios (7 : 10 to 2 : 1) and Kolliphor® P188 and Tween® 80 concentration (>3.0% w/w) aiming forz-average in the range of 100-300 nm for macrophage delivery. The NLC obtained by high-pressure homogenization showed lowz-averages (<350 nm), polydispersity (<0.3), and encapsulation efficiency close to 100%. DSC/TG and microscopy in combination proved to be a powerful tool to select the solid lipid. The relationship among the variables, demonstrated by a linear mathematical model using RSM, allowed generating a design space. This design space showed the limits in which changes in the variables influenced thez-average. Therefore, these drug delivery systems have the potential to improve the availability of affordable medicines due to the low cost of raw materials, using well established, reliable, and feasible scale-up technology.
authors.affiliation: Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, Professor Lineu Prestes Av 580, Cidade Universitária, 05508-000 São Paulo, SP, Brazil.
authors.forename: Lis Marie
authors.identifier: 0000-0001-6409-0672
authors.initials: LM
authors.lastname: Monteiro
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 8613 114th St NW, Edmonton, AB, Canada T6G 2H7.
authors.forename: Raimar
authors.initials: R
authors.lastname: Löbenberg
authors.affiliation: Seroepidemiology, Cellular and Molecular Immunology Laboratory, Institute of Tropical Medicine, University of São Paulo, Dr. Enéas de Carvalho Aguiar 470, Jardim América, 05403-000 São Paulo, SP, Brazil.
authors.forename: Paulo Cesar
authors.initials: PC
authors.lastname: Cotrim
authors.affiliation: Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, Professor Lineu Prestes Av 580, Cidade Universitária, 05508-000 São Paulo, SP, Brazil.
authors.forename: Gabriel Lima
authors.identifier: 0000-0001-7590-3587
authors.initials: GL
authors.lastname: Barros de Araujo
authors.affiliation: Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, Professor Lineu Prestes Av 580, Cidade Universitária, 05508-000 São Paulo, SP, Brazil.
authors.forename: Nádia
authors.identifier: 0000-0002-5271-5468
authors.initials: N
authors.lastname: Bou-Chacra
mesh_terms: D000704:Analysis of Variance; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D007896:Leishmaniasis / Q000188:drug therapy*; D008055:Lipids / Q000737:chemistry*; D008853:Microscopy; D049329:Nanostructures / Q000737:chemistry*; D009285:Naphthoquinones / Q000494:pharmacology / Q000627:therapeutic use*; D012995:Solubility; D055672:Static Electricity
chemical_list: D004337:Drug Carriers; D008055:Lipids; D009285:Naphthoquinones; C046326:buparvaquone