Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.
Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil; Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.
Carbohydr Polym. 2021 Jan 15;252:117184. doi: 10.1016/j.carbpol.2020.117184. Epub 2020 Oct 5.
The emergence of multidrug-resistant (MDR) bacteria is a global problem, by reducing the effectiveness of traditional antibiotics and decreasing the therapeutic arsenal to treat bacterial infections. This has led to an increase in researches about how to overcome this resistance to antibiotics. One strategy is the repositioning (or repurposing) of existing drugs not previously used to combat microorganisms, rather than the development of new drugs. Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRIs) and is considered one of the first highly selective antidepressants of the monoamine neurotransmitter serotonin (5-HT). The objective of this study is to prepare and physically characterize fluoxetine microparticles with galactomannan and evaluate their efficacy against strains of Staphylococcus aureus sensitive and resistant to methicillin. The microparticles were analyzed by differential scanning calorimetry (DSC), infrared analysis (IR) and X-ray diffraction (XRD). In addition, the percentage of encapsulation efficiency (EE%) and drug release kinetics were determined in vitro, along with the determination of the minimum inhibitory concentration (MIC) and evaluation of the action against biofilms. Physical tests were conducted to characterize galactomannan (GAL), FLX, oxacillin (OXA) and the galactomannan/fluoxetine microparticles (GFM). The EE% value was 98 % and, in regard the release, tests with the microparticles released about 60 % of the drug in 200 min. The isolated MIC results for FLX (255 μg/mL) and OXA MIC (1.97-15.62 μg/mL) showed that the strains were resistant. Furthermore, in the biofilms, microparticles showed statically significant improvement for all concentrations used. The study revealed that fluoxetine encapsulated in microparticles has the potential to act as an effective antimicrobial agent.
多药耐药（MDR）细菌的出现是一个全球性问题，它降低了传统抗生素的有效性，并减少了治疗细菌感染的治疗武器库。这导致了人们越来越多地研究如何克服这种抗生素耐药性。一种策略是重新定位（或重新利用）以前未用于对抗微生物的现有药物，而不是开发新药物。氟西汀（FLX）是一种选择性 5-羟色胺再摄取抑制剂（SSRIs），被认为是第一种高度选择性的单胺神经递质 5-羟色胺（5-HT）抗抑郁药之一。本研究的目的是制备并物理表征半乳甘露聚糖氟西汀微球，并评估其对耐甲氧西林金黄色葡萄球菌敏感和耐药菌株的疗效。通过差示扫描量热法（DSC）、红外分析（IR）和 X 射线衍射（XRD）对微球进行分析。此外，还测定了体外包封效率（EE%）和药物释放动力学，并测定了最小抑菌浓度（MIC），评估了对生物膜的作用。进行了物理测试以表征半乳甘露聚糖（GAL）、FLX、苯唑西林（OXA）和半乳甘露聚糖/氟西汀微球（GFM）。EE%值为 98%，而关于释放，微球的释放测试在 200 分钟内释放了约 60%的药物。FLX（255 μg/mL）和 OXA MIC（1.97-15.62 μg/mL）的分离 MIC 结果表明，这些菌株具有耐药性。此外，在生物膜中，微球在所有使用浓度下均显示出统计学上显著的改善。该研究表明，包封在微球中的氟西汀有可能作为一种有效的抗菌剂。
