Abstract
Buparvaquone (BPQ), a veterinary drug, was formulated as nanostructured lipid carriers (NLC) for leishmaniases treatment. The formulation design addressed poor water solubility of BPQ and lack of human drug delivery system. The DSC/TG and microscopy methods were used for solid lipids screening. Softisan® 154 showed highest BPQ solubility in both methods. The BPQ solubility in liquid lipids using HPLC revealed Miglyol® 812 as the best option. Response surface methodology (RSM) was used to identify the optimal Softisan154 : Miglyol 812 ratios (7 : 10 to 2 : 1) and Kolliphor® P188 and Tween® 80 concentration (>3.0% w/w) aiming for z-average in the range of 100–300 nm for macrophage delivery. The NLC obtained by high-pressure homogenization showed low z-averages (<350 nm), polydispersity (<0.3), and encapsulation efficiency close to 100%. DSC/TG and microscopy in combination proved to be a powerful tool to select the solid lipid. The relationship among the variables, demonstrated by a linear mathematical model using RSM, allowed generating a design space. This design space showed the limits in which changes in the variables influenced the z-average. Therefore, these drug delivery systems have the potential to improve the availability of affordable medicines due to the low cost of raw materials, using well established, reliable, and feasible scale-up technology.
Highlights
Over the past decades, improper prescription and lack of patient compliance, due to severe toxicity of conventional medicines, have caused the development of widespread parasite resistance in leishmaniases
No new drug substances have been introduced in the therapy, and there are no effective vaccines available to prevent or heal this neglected tropical disease [1, 2]
The low water solubility of BPQ limits its bioavailability, which is the main challenge for developing a drug delivery system for enhancing its therapeutic efficacy
Summary
Improper prescription and lack of patient compliance, due to severe toxicity of conventional medicines, have caused the development of widespread parasite resistance in leishmaniases. The development of lipid nanoparticles is one of the most promising alternatives to overcome this limitation Such delivery systems have the ability to overcome biological barriers, increase therapeutic efficacy, reduce toxicity, and allow drug release at the specific site [3, 4]. These colloidal carriers are quickly taken up by cells from the mononuclear phagocyte system [5], which are the host cells of the leishmaniases parasite infection. This mechanism makes nanoparticles an attractive vector for passive targeting of antileishmanial drug substances [6]. Lipid-based nanoparticles represent an opportunity to improve the leishmaniases therapy
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