RESUMO
The aim of this study was to evaluate the efficacy and non-toxicity of ciclopirox olamine-loaded liposomes against Cryptococcus neoformans clinical isolates. Initially, 24-1 fractional experimental design was carried out to obtain an optimized formulation of liposomes containing CPO (CPO-LipoC), which were then used to prepare stealth liposomes (CPO-LipoS). Liposomal formulations were characterized by their mean size diameter, polydispersity index (PDI), and drug encapsulation efficiency (EE%). Immunosuppressed mice were exposed to CPO-LipoS at 0.5 mg/kg/day for 14 days to verify possible histopathological alterations in the liver and kidneys. Immunosuppressed mice infected with C. neoformans were treated with CPO-LipoS at 0.5 mg/kg/day for 14 days to quantify the fungal burden in spleen, liver, lungs, and brain. CPO-LipoS presented a mean size diameter, PDI, and EE% of 101.4 ± 0.7 nm, 0.307, and 96.4 ± 0.9%, respectively. CPO-LipoS was non-toxic for the liver and kidneys of immunosuppressed mice. At the survival curve, all infected animals submitted to treatment with CPO-LipoS survived until the end of the experiment. Treatment with CPO-LipoS reduced C. neoformans cells in the spleen (59.3 ± 3.4%), liver (75.0 ± 3.6%), lungs (75.7 ± 6.7%), and brain (54.2 ± 3.2%). CPO-LipoS exhibit antifungal activity against C. neoformans, and the encapsulation of CPO into stealth liposomes allows its use as a systemic drug for treating cryptococcosis.
Assuntos
Criptococose , Cryptococcus neoformans , Animais , Camundongos , Ciclopirox/uso terapêutico , Lipossomos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Criptococose/tratamento farmacológico , Criptococose/microbiologiaRESUMO
Doxorubicin (DOX) is a natural antibiotic with antineoplastic activity. It has been used for over 40 years and remains one of the most used drugs in chemotherapy for a variety of cancers. However, cardiotoxicity limits its use for long periods. To overcome this limitation, encapsulation in smart drug delivery systems (DDS) brings advantages in comparison with free drug administration (i.e., conventional anticancer drug therapy). In this review, we present the most relevant nanostructures used for DOX encapsulation over the last 10 years, such as liposomes, micelles and polymeric vesicles (i.e., polymersomes), micro/nanoemulsions, different types of polymeric nanoparticles and hydrogel nanoparticles, as well as novel approaches for DOX encapsulation. The studies highlighted here show these nanoformulations achieved higher solubility, improved tumor cytotoxicity, prolonged DOX release, as well as reduced side effects, among other interesting advantages.
Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Micelas , Neoplasias/tratamento farmacológicoRESUMO
Colloidal systems based on lipids have attracted attention during the last two decades as a delivery method of drugs that are poorly soluble in water. The investigations carried out have focused on the development of different formulations using a wide variety of excipients and active molecules. However, there is no consensus on the structure of the particles in these colloidal systems. This is partly due since there are few studies oriented to understand both the preferential location of the drug in the particle and the arrangement of the lipids and the stabilizing agents during the particle formation. As a contribution in this sense, in this review the most common materials and preparation methods to obtain lipid particles are presented. Also, the particle characteristics, including the shape, size and size distribution, zeta potential, drug load capacity and drug entrapment efficiency are synthesized and analyzed with the help of scientometrics tools. Emphasis has been placed on the latest advances regarding the particle structure especially as it relates to the drug release behavior. In addition to the available evidence, a model of particle structure based on the formation of the different polymorphic forms of the solid lipid because of the starting materials and the processing conditions is proposed. In general, the importance of obtaining a detailed knowledge of the structure of the lipid nanoparticles is highlighted, which is useful for the rational design of this type of nanocarriers and propose solutions to the challenges involved in their formulation.