Silva Marina Goulart Da, Cardoso Jéssica Ferreira, Perasoli Fernanda Barçante, Branquinho Renata Tupinambá, Mourão Renata Silva, Tavares Harley Da Silva, Xocaira Maria Luiza Costa Trench, Guimarães Daniel Silqueira Martins, Viana Gustavo Henrique Ribeiro, Varotti Fernando De Pilla, Silva Gisele Rodrigues Da
Federal University of São João del-Rei, Campus Centro Oeste Dona Lindu, Sebastião Gonçalves Coelho 400, Chanadour, 35.501-296, Divinópolis, Minas Gerais, Brazil.
School of Pharmacy, Federal University of Ouro Preto, Campus Morro do Cruzeiro w/n, Bauxita, 35.400-000, Ouro Preto, Minas Gerais, Brazil.
Eur J Pharm Sci. 2020 Aug 1;151:105382. doi: 10.1016/j.ejps.2020.105382. Epub 2020 May 26.
Malaria treatment is based on a reduced number of antimalarial drugs, and drug resistance has emerged, leading to the search for new antimalarial drugs incorporated into pharmaceutical formulations. In this study, 10-(4,5-dihydrothiazol-2-yl)thio)decan-1-ol) (thiazoline), a synthetic analog of 3-alkylpiridine marine alkaloid, and a potent antimalarial substance, was incorporated into O/W nanoemulsion. This formulation was prepared by a 2 factorial design. It was characterized by globule diameter, polydispersity index, zeta potential, encapsulation efficiency, in vitro thiazoline release at pH 2 and 6.86, and accelerated stability. In vitro and in vivo antimalarial activity was determined against P. falciparum and P. berghei, respectively. Thiazoline nanoemulsion showed 248.8 nm of globule diameter, 0.236 of polydispersity index, -38.5 mV of zeta potential, 96.92% encapsulation efficiency, and it was stable for 6 months. Thiazoline release profiles differed in acidic and neutral media, but in both cases, the nanoemulsion controlled and prolonged the thiazoline delivery. Thiazoline nanoemulsion exerted in vitro antimalarial activity against the parasite (IC = 1.32 µM), and it significantly reduced the in vivo parasitemia for 8 days without increasing the survival time of animals. Therefore, the thiazoline nanoemulsion represents a strategy to treat malaria combining an antimalarial candidate and a new nanocarrier.
疟疾治疗依赖于数量有限的抗疟药物，而耐药性已经出现，这促使人们寻找新的抗疟药物并将其制成药物制剂。在本研究中，将3-烷基吡啶海洋生物碱的合成类似物、强效抗疟物质10-(4,5-二氢噻唑-2-基)硫代)癸-1-醇（噻唑啉）掺入水包油纳米乳剂中。该制剂通过二因素设计制备。通过球粒直径、多分散指数、zeta电位、包封效率、在pH 2和6.86条件下噻唑啉的体外释放以及加速稳定性对其进行表征。分别针对恶性疟原虫和伯氏疟原虫测定了体外和体内抗疟活性。噻唑啉纳米乳剂的球粒直径为248.8 nm，多分散指数为0.236，zeta电位为-38.5 mV，包封效率为96.92%，并且在6个月内保持稳定。噻唑啉在酸性和中性介质中的释放曲线不同，但在两种情况下，纳米乳剂都能控制并延长噻唑啉的释放。噻唑啉纳米乳剂对寄生虫具有体外抗疟活性（IC = 1.32 µM），并且在不增加动物存活时间的情况下，显著降低了体内寄生虫血症达8天。因此，噻唑啉纳米乳剂代表了一种将抗疟候选药物与新型纳米载体相结合来治疗疟疾的策略。
