Development of Lipid Nanocarriers for Tuberculosis Treatment: Evaluation of Suitable Excipients and Nanocarriers

Abstract

Background: Lipid nanocarriers have been widely tested as drug delivery systems to treat diseases due to their bioavailability, controlled release, and low toxicity. For the pulmonary route, the Food and Drug Administration favors the use of substances generally recognized as safe, as well as biodegradable and biocompatible to minimize the possibility of toxicity. Tuberculosis (TB) remains a public health threat worldwide, mainly due to the long treatment duration and adverse effects. Therefore, new drug delivery systems to treat TB are needed. Objective: Physicochemical characterization of different lipid-based nanocarriers was used to optimize carrier properties. Optimized systems were incubated with Mycobacterium tuberculosis to assess whether lipid-based systems act as an energy source for the bacteria, which could be counterproductive to therapy. Method: Several excipients and surfactants were evaluated to prepare different types of nanocarriers using high-pressure homogenization. Results: A mixture of trimyristin with castor oil was chosen as the lipid matrix after differential scanning calorimetry analysis. A mixture of egg lecithin and PEG-660 stearate was selected as an optimal surfactant system as this mixture formed the most stable formulations. Three types of lipid nanocarriers, solid lipid nanoparticles, nanostructured lipid carriers (NLC), and Nano emulsions, were prepared, with the NLC systems showing the most suitable properties for further evaluation. It may provide the advantages of increasing the entrapment efficiency, drug release, and the ability to be lyophilized, producing powder for pulmonary administration being an alternative to entrap poor water-soluble molecules. Conclusion: Furthermore, the NLC system can be considered for use as a platform for the treatment of TB by the pulmonary route.

Development of a Novel Lipid-Based Nanosystem Functionalized with WGA for Enhanced Intracellular Drug Delivery

“…This change in zeta potential is a strong indication that the protein has bound to the surface of the nanocarriers. These data corroborate with the results observed in our study [ 20 ].…”

“…One strategy that has been recently explored is administering inhaled drugs by the pulmonary route aiming to reach higher local drug concentrations. With the use of nanotechnology, it is possible to use targeting moieties that directly or indirectly can make inhalable medicine delivery systems attractive as the drugs can reach the target site of the infection at an intracellular level [ 20 ].…”

“…The binding of lectins to the alveolar epithelium and subsequent endocytosis, as it occurs in the intestine, was already described [ 37 ]. In our previous studies [ 20 ], different lipid nanocarriers were produced and showed no cytotoxicity in the concentration range that macrophages were exposed to. Furthermore, once the nanocarriers were exposed to M. tuberculosis , no increase in growth was observed meaning that the products of the lipid metabolism would not be used as an energy source for the microorganism.…”

“…The NLC ( Table 1 ) was prepared following a method previously described [ 20 ]. Briefly, the oil phase containing trimyristin, castor oil, and egg lecithin E80 was melted at 82 °C, under stirring (1500 rpm) until a homogeneous melt was achieved.…”

“…Aiming to circumvent the limitations of conventional therapeutic schemes and propose new pharmacological alternatives treatments, in this study, we functionalized with WGA lectin our previously described nanostructured lipid nanocarriers [ 20 ] and entrapped them with lipophilic compounds (quercetin, Nile red, and conjugated polymer CNPPV) to better understand how they are released from the nanocarriers and also to analyze the cellular uptake. We hypothesized that nanoparticles functionalized with WGA could improve the intracellular drug payload via lectin receptors expressed on macrophages.…”