A Functional Wound Dressing as a Potential Treatment for Cutaneous Leishmaniasis.

Cutaneous leishmaniasis (CL) is a parasitic disease characterized by progressive skin sores. Currently, treatments for CL are limited to parenteral administration of the drug, which presents severe adverse effects and low cure rates. Therefore, this study aimed to develop poly(vinyl-alcohol) (PVA) hydrogels containing Amphotericin B (AmB) intended for topical treatment of CL. Hydrogels were evaluated in vitro for their potential to eliminate promastigote forms of Leishmania spp., to prevent secondary infections, to maintain appropriate healing conditions, and to offer suitable biocompatibility. AmB was incorporated into the system in its non-crystalline state, allowing it to swell more and faster than the system without the drug. Furthermore, the AmB release profile showed a continuous and controlled behavior following Higuchi´s kinetic model. AmB-loaded-PVA-hydrogels (PVA-AmB) also showed efficient antifungal and leishmanicidal activity, no cytotoxic potential for VERO cells, microbial impermeability and water vapor permeability compatible with the healthy skin's physiological needs. Indeed, these results revealed the potential of PVA-AmB to prevent secondary infections and to maintain a favorable environment for the healing process. Hence, these results suggest that PVA-AmB could be a suitable and efficient new therapeutic approach for the topical treatment of CL.

Dual alginate-lipid nanocarriers as oral delivery systems for amphotericin B.

Amphotericin B (AmB) is the first-choice drug to treat several fungal infections. However, due to its low solubility it can only be administrated intravenously. Nanostructured lipid carriers (NLC) have the ability to encapsulate hydrophobic drugs in an aqueous matrix, making them interesting for use in alternative drug delivery systems for AmB. Their combination with stimuli-sensitive polymers such as alginate can be used as a strategy to protect acid sensitive molecules from gastric acid. The proposal of this work was to develop a dual-strategy hydrogel/NLC delivery system for amphotericin B. NLCs were produced by high-pressure homogenization and their size and stability were assessed by dynamic light scattering and electron transmission microscopy. The NLCs presented low cytotoxicity and high selectivity at neutral pH. Alginate hydrogels were successfully produced by the ionic gelation method and characterized using optical microscopy. The hydrogels were tested for their pH-selectivity, cytotoxicity and drug delivery profile. Swelling degree and drug delivery profiles suggested that drug delivery is stimulated as the alginate particles swell and that NLC particles maintain their structure even after rehydration, indicating these systems can be used for oral delivery of AmB.

Understanding Drug Release Data through Thermodynamic Analysis.

Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS) is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB) kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas-Sahlin and Higuchi models, respectively. The thermodynamic parameters corroborate these findings, revealing that the AmB release from the evaluated systems was an endothermic and non-spontaneous process. Thermodynamic parameters can be used to explain the drug kinetic release profiles. Such an approach is of utmost importance for DDS containing insoluble compounds, such as AmB, which is associated with an erratic bioavailability.