Lívia Palmerston Mendes

Biodegradable nanoparticles designed for drug delivery: The number of nanoparticles impacts on cytotoxicity.

Nanostructured drug delivery systems are based on biocompatible and biodegradable components. Composition, size and membrane surface properties are characteristics that may influence cell viability in cytotoxicity assays. In this work, four nanostructured systems commonly used for drug delivery were prepared and cytotoxicity was evaluated on human lymphocytes and Balb/c 3T3 fibroblasts. The hemolytic potential was also investigated. Polymeric nanocapsules (NC) and nanospheres (NS), nanostructured lipid carriers (NLC) and liposomes were prepared and characterized for size, distribution, zeta potential and number per volume of the colloidal dispersion. Cell viability was evaluated, 24 and 48h, by MTT and neutral red assays (NR). Cells were incubated with each particle in eight different dilutions varying from 2.1×10(4) to 2.1×10(11)particles/mL. Diameter of nanoparticles was between 130 and 200nm, all samples exhibited narrow size distribution (polydispersity index below 0.1) and zeta potential varied from -6.8 to -19.5mV. NC, NS and NLC reduced cell viability in a dilution dependent manner. For these nanoparticles, the higher number of particles induced cell death for both cell types. Liposomes did not cause loss of cell viability even at the highest number of particles. Results suggest that, depending on the kind of nanoparticle, the number of particles in the dispersion can negatively influence cell viability in pre-clinical drug development.

Characterization, nanoparticle self-organization, and Monte Carlo simulation of magnetoliposomes.

In this work we have developed and implement a new approach for the study of magnetoliposomes using Monte Carlo simulations. Our model is based on interaction among nanoparticles considering magnetic dipolar, van der Waals, ionic-steric, and Zeeman interaction potentials. The ionic interaction between nanoparticles and the lipid bilayer is represented by an ionic repulsion electrical surface potential that depends on the nanoparticle-lipid bilayer distance and the concentration of ions in the solution. A direct comparison among transmission electron microscopy, vibrating sample magnetometer, dynamic light scattering, nanoparticle tracking analysis, and experimentally derived static magnetic birefringence and simulation data allow us to validate our implementation. Our simulations suggest that confinement plays an important role in aggregate formation.

In Vivo Vaginal Fungal Load Reduction After Treatment with Itraconazole-Loaded Polycaprolactone-Nanoparticles

Itraconazole (ITZ) has a broad spectrum of action and is commonly used for the treatment of fungal infections. Topic administration of ITZ is a promising strategy to improve vulvovaginal candidiasis treatment, which can be further optimized by its encapsulation in nanoparticles to increase drug delivery and reduce ITZ toxicity. In this work, we designed polycaprolactone nanoparticles containing ITZ and evaluated in vivo the efficacy of this yet unexplored approach. Nanocapsules (ITZ-NC) and nanospheres (ITZ-NS) were obtained by nanoprecipitation. ITZ-NC presented encapsulation efficiency of 99%, mean diameter of 190 nm, PDI 0.1 and zeta potential of -15 mV. ITZ-NS showed encapsulation efficiency of 97%, mean diameter of 120 nm, PDI 0.1 and zeta potential of -10 mV. Both particles were efficiently freeze-dried using 10% trehalose + 10% sucrose. Nanoparticles were then incorporated in a viscous formulation for vaginal application in female Balb/C mice infected with Candida albicans. Fungal load was significantly reduced in infected animals after treatment with ITZ-NC but not with ITZ-NS, compared to animals treated with ITZ solution. Histological analysis showed a clear difference between vaginal tissues of ITZ-NC and ITZ-NS and ITZ solution-treated animals, which correlated with IL-1β and TNF-α quantification. Animals treated with ITZ-NC showed reduced cytokine levels and healthy tissue characteristics, while animals treated with ITZ-NS and ITZ solution showed increased IL-1β and TNF-α levels and typical tissue inflammation. Our results demonstrate the potential of ITZ-NC to improve the treatment of vulvovaginal candidiasis after topical application in the vagina, opening new perspectives for the treatment of this disease.