RESUMO
Millions of people worldwide are affected by leishmaniasis, caused by the Leishmania parasite. Effective treatment is challenging due to the biological complexity of the parasite, drug toxicity, and increasing resistance to conventional drugs. To combat this disease, the development of specific strategies to target and selectively eliminate the parasite is crucial. This Review highlights the importance of amino acids in the developmental stages of Leishmania as a factor determining whether the infection progresses or is suppressed. It also explores the use of peptides as alternatives in parasite control and the development of novel targeted treatments. While these strategies show promise for more effective and targeted treatment, further studies to address the remaining challenges are imperative.
Assuntos
Aminoácidos , Antiprotozoários , Leishmania , Leishmaniose , Peptídeos , Leishmania/efeitos dos fármacos , Aminoácidos/química , Leishmaniose/tratamento farmacológico , Leishmaniose/parasitologia , Humanos , Peptídeos/farmacologia , Peptídeos/química , Antiprotozoários/farmacologia , Antiprotozoários/química , AnimaisRESUMO
Tuberculosis is an infectious bacterial disease that causes millions of deaths worldwide. Current treatment recommended by WHO is effective, however it is an extensive and arduous process associated to severe adverse effects, which induces a low patient compliance and the emerging of multidrug resistant tuberculosis. Thus, as a main goal of this study, rifampicin nanoparticles were surface functionalized with a tuftsin-modifed peptide to selectively recognize receptors located on infected alveolar macrophages, enhancing nanoparticles uptake by these cells and improving antimycobacterial activity. A tuftsin-based modified peptide was synthesized and successfully attached to nanoparticles interface (NP-pRIF). In parallel, nanoparticles without peptide were also developed for comparison (NP-RIF). Physicochemical characterization demonstrated that stable and monodisperse nanodelivery systems were obtained, with a controlled drug release profile and non-cytotoxic potential. Moreover, nanoparticles containing peptide were significantly more internalized by macrophages than nanoparticles without peptide over a wide range of time. Both nanoparticles were 2-fold more effective against M. tuberculosis than free rifampicin, suggesting NP-pRIF as a promising strategy for the management of tuberculosis treatment.
Assuntos
Antituberculosos/farmacologia , Lipídeos/química , Macrófagos/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Nanoestruturas/química , Rifampina/farmacologia , Animais , Antituberculosos/química , Antituberculosos/farmacocinética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/fisiologia , Rifampina/química , Rifampina/farmacocinética , Tuftsina/químicaRESUMO
Ultrasound is widely used in several chemical reactions and other process, including production of nanocapsules by in situ polymerization. In this work, the main objective was to evaluate the impacts and viability of successive ultrasound application in nanoemulsions to obtain nanocapsules. Initiator potassium persulfate (KPS) concentration, number of ultrasound cycles and reaction time influences on polymerization efficiency and droplet size were evaluated. This work revealed the successful in situ production of nanocapsules using successive shorts cycles of ultrasound. Number of cycles was the only parameter that not exerted significant influence in polymerization yield. Particle size decay was observed in all nanoemulsions after the first ultrasound application, the same was not observed in further cycles. Gravimetric assessment showed remarkable increase of monomer conversion, indicating that once started polymerization continued at least until 28 days after ultrasound application. Concluding, ultrasound short cycles can be used with no harm to formulation, if carefully performed and, furthermore is a potential cost-effective route for polymerization reactions.