Pereira Emiliane Daher, da Silva Dutra Luciana, Paiva Thamiris Franckini, de Almeida Carvalho Larissa Leite, Rocha Helvécio Vinícius Antunes, Pinto José Carlos
Programa de Engenharia Química/COPPE, Universidade Federal do Rio de Janeiro, Cidade Universitária, CP: 68502, Rio de Janeiro 21941-972, RJ, Brazil.
SENAI CETIQT, Instituto SENAI de Inovação em Biossintéticos e Fibras, Cidade Universitária, Rua Fernando de Souza Barros, Rio de Janeiro 21941-857, RJ, Brazil.
Materials (Basel). 2023 Apr 26;16(9):3382. doi: 10.3390/ma16093382.
Approximately 1 billion people are affected by neglected diseases around the world. Among these diseases, schistosomiasis constitutes one of the most important public health problems, being caused by and treated through the oral administration of praziquantel (PZQ). Despite being a common disease in children, the medication is delivered in the form of large, bitter-tasting tablets, which makes it difficult for patients to comply with the treatment. In order to mask the taste of the drug, allow more appropriate doses for children, and enhance the absorption by the body, different polymer matrices based on poly(methyl methacrylate) (PMMA) were developed and used to encapsulate PZQ. Polymer matrices included PMMA nano- and microparticles, PMMA-co-DEAEMA (2-(diethylamino)ethyl methacrylate), and PMMA-co-DMAEMA (2-(dimethylamino)ethyl methacrylate) microparticles. The performances of the drug-loaded particles were characterized in vitro through dissolution tests and in vivo through pharmacokinetic analyses in rats for the first time. The in vitro dissolution studies were carried out in accordance with the Brazilian Pharmacopeia and revealed a good PZQ release profile in an acidic medium for the PMMA-DEAEMA copolymer, reaching values close to 100 % in less than 3 h. The in vivo pharmacokinetic analyses were conducted using free PZQ as the control group that was compared with the investigated matrices. The drug was administered orally at doses of 60 mg/kg, and the PMMA-co-DEAEMA copolymer microparticles were found to be the most efficient release system among the investigated ones, reaching a C value of 1007 ± 83 ng/mL, even higher than that observed for free PZQ, which displayed a C value of 432 ± 98 ng/mL.
全球约有10亿人受到被忽视疾病的影响。在这些疾病中，血吸虫病是最重要的公共卫生问题之一，由吡喹酮（PZQ）引起并通过口服吡喹酮进行治疗。尽管这种疾病在儿童中很常见，但药物是以大的、味苦的片剂形式给药，这使得患者难以遵医嘱治疗。为了掩盖药物的味道，使儿童能够服用更合适的剂量，并增强身体对药物的吸收，人们开发了不同的基于聚甲基丙烯酸甲酯（PMMA）的聚合物基质，并用于包裹吡喹酮。聚合物基质包括PMMA纳米颗粒和微米颗粒、PMMA-co-DEAEMA（甲基丙烯酸2-(二乙氨基)乙酯）和PMMA-co-DMAEMA（甲基丙烯酸2-(二甲氨基)乙酯）微米颗粒。首次通过体外溶出试验和大鼠体内药代动力学分析对载药颗粒的性能进行了表征。体外溶出研究按照巴西药典进行，结果显示PMMA-DEAEMA共聚物在酸性介质中具有良好的吡喹酮释放曲线，在不到3小时内释放值接近100%。体内药代动力学分析以游离吡喹酮作为对照组，与所研究的基质进行比较。药物以60 mg/kg的剂量口服给药，结果发现PMMA-co-DEAEMA共聚物微米颗粒在所研究的体系中是最有效的释放系统，C值达到1007±83 ng/mL，甚至高于游离吡喹酮的C值（432±98 ng/mL）。
