Sustained-release hydrogels of ivermectin as alternative systems to improve the treatment of cutaneous leishmaniasis.

Background: Leishmaniasis is a neglected tropical disease and its cutaneous form manifests as ulcers or nodules, generally in exposed parts of the body. This work aimed to develop ivermectin (IVM) thermosensitive hydrogels as topical formulations to improve cutaneous leishmaniasis treatment. Materials & methods: Hydrogels based on poloxamers 407 and 188 with different concentrations of IVM were prepared and rheologically characterized. The IVM release profiles were obtained and mathematically analyzed using the Lumped model. Results: The formulation containing 1.5% w/w of IVM presented an adequate gelling temperature, an optimal complex viscosity and elastic modulus. Hydrogels allowed to modulate the release of IVM. Conclusion: IVM thermosensitive hydrogels can be considered a valuable alternative to improve the treatment of cutaneous leishmaniasis.

Evaluation of the Drug Release Kinetics in Assembled Modular Systems Based on the Dome Matrix Technology.

Mathematical models are an important tool in pharmaceutical formulations development, to evaluate in vitro and in vivo drug release processes and to optimize the design of new systems. Dome Matrix technology allows the combination of modules with different types of drugs, doses, and releases kinetics. This work aimed to design drug release systems based on Dome Matrix technology, with different swelling and erosion properties, to obtain complex drug release profiles and analyze them with simple mathematical models. Most of the release profiles followed a sigmoid curve, with an inflection point corresponding to a change in the release rate behavior. The experimental data were fitted with a simple model recently developed, named the Dual Release model, which consists in the combination of a modified Korsmayer-Peppas model from the beginning to the inflection point and the Lumped model from there until the end. This approach allowed determining relevant pharmaceutical parameters, such as the maximum release rate and the dissolution efficiency, among others. The use of the Dual Release model and the pharmaceutical parameters that characterize the different Dome Matrix modules allows optimizing the choice of the composition and the configuration during the development of a drug delivery system.

Preparation and Characterization of Poloxamer 407 Solid Dispersions as an Alternative Strategy to Improve Benznidazole Bioperformance.

Benznidazole (BZL), the first line drug for Chagas disease treatment, presents a low solubility, limiting the possibilities for its formulation. In this work, solid dispersions' (SDs) technology was exploited to increase BZL kinetic solubility and dissolution rate, seeking for an improvement in its bioperformance. A physical mixture (PM) and an SD using Poloxamer 407 as carrier were prepared and characterized. Dissolution tests were performed, and data were analyzed with the lumped model, which allowed to calculate different parameters of pharmaceutical relevance. A bioactivity assay was also carried out to probe the SD anti-trypanocidal activity. Among the most relevant results, the initial dissolution rate of the BZL SD was near 3, 4 and about 400-fold faster than the PM, a commercial formulation (CF) and an extracted BZL, respectivley. The times needed for an 80% of drug dissolution were 3.6 (SD), 46.4 (PM), and 238.7 min (CF); while the dissolution efficiency values at 30 min were 85.2 (SD), 71.2 (PM), and 65.0% (CF). Survival curves suggested that using Poloxamer 407 as carrier did not alter the anti-trypanocidal activity of BZL. These results allow to conclude that SDs can be an effective platform for immediate release of BZL in an oral administration.

How long can culturable bacteria and total DNA persist in environmental waters? The role of sunlight and solid particles.

In this work, sunlight inactivation of two indicator bacteria in freshwater, with and without solid particles, was studied and the persistence of culturable cells and total DNA was compared. Environmental water was used to prepare two matrices, with and without solid particles, which were spiked with Escherichia coli and Enterococcus faecalis. These matrices were used to prepare microcosm bags that were placed in two containers: one exposed to sunlight and the other in the dark. During one month, samples were removed from each container and detection was done by membrane filter technique and real-time PCR. Kinetic parameters were calculated to assess sunlight effect. Indicator bacteria without solid particles exposed to sunlight suffered an immediate decay (<4h) compared with the ones which were shielded from them. In addition, the survival of both bacteria with solid particles varied depending on the situation analyzed (T99 from 3 up to 60days), being always culturable E. coli more persistent than E. faecalis. On the other side, E. faecalis DNA persisted much longer than culturable cells (T99>40h in the dark with particles). In this case active cells were more prone to sunlight than total DNA and the protective effect of solid particles was also observed. Results highlight that the effects caused by the parameters which describe the behavior of culturable microorganisms and total DNA in water are different and must be included in simulation models but without forgetting that these parameters will also depend on bacterial properties, sensitizers, composition, type, and uses of the aquatic environment under assessment.

Increasing capacity for environmental engineering in Salta, Argentina.

BACKGROUND: The Fogarty International Center (FIC) of the United States National Institutes of Health includes the International Training and Research in Environmental and Occupational Health (ITREOH) Program. The "International Training Program in Environmental Toxicology and Public Health" Center, funded in 2002 is based at the University of California, Davis, and is part of the ITREOH group of Centers. It has major efforts focused at the public universities in Montevideo, Uruguay, and Salta, Argentina. RESULTS: Training and research efforts in Salta begun in 2005 in the College of Engineering. A donated used real-time PCR machine was the starting point and the initial FIC support was instrumental to face other problems including physical space, research projects and grants, trainees, training, networking, and distractions/opportunities in order to develop local capacities in Environmental Engineering using modern methodology. After 6 years of successful work, the Salta center has become a reference Center in the field, and is still growing and consolidating. CONCLUSIONS: This program has had a significant impact locally and regionally. The model used in Argentina could be easily adapted to other fields or types of projects in Argentina and in other developing countries.