Exploring the Toxicity, Lung Distribution, and Cellular Uptake of Rifampicin and Ascorbic Acid-Loaded Alginate Nanoparticles as Therapeutic Treatment of Lung Intracellular Infections

Abstract

Nanotechnology is a very promising technological tool to combat health problems associated with the loss of effectiveness of currently used antibiotics. Previously, we developed a formulation consisting of a chitosan and tween 80-decorated alginate nanocarrier that encapsulates rifampicin and the antioxidant ascorbic acid (RIF/ ASC), intended for the treatment of respiratory intracellular infections. Here, we investigated the effects of RIF/ASC-loaded NPs on the respiratory mucus and the pulmonary surfactant. In addition, we evaluated their cytotoxicity for lung cells in vitro, and their biodistribution on rat lungs in vivo after their intratracheal administration. Findings herein demonstrated that RIF/ASC-loaded NPs display a favorable lung biocompatibility profile and a uniform distribution throughout lung lobules. RIF/ASC-loaded NPs were mainly uptaken by lung macrophages, their primary target. In summary, findings show that our novel designed RIF/ASC NPs could be a suitable system for antibiotic lung administration with promising perspectives for the treatment of pulmonary intracellular infections.

Pulmonary Safety Profile of Esc Peptides and Esc-Peptide-Loaded Poly(lactide-co-glycolide) Nanoparticles: A Promising Therapeutic Approach for Local Treatment of Lung Infectious Diseases

“…Nevertheless, a limited number of studies have been performed to confirm the safety of PLGA NPs in the short and long term, especially in the lung compartment [43][44][45][46].…”

Modulation of engineered nanomaterial interactions with organ barriers for enhanced drug transport

“…Strategies not focused on overcoming the lung biological barrier, for example alveolar macrophage targeting therapies, are not considered in the scope of this review. 49 2.2.1. Core material.…”

Advances in therapeutic nanodrug delivery systems for infectious lung diseases: a review

“…Therefore, CS modification has good potential for application in local mucosal drug delivery. Scolari et al [35] have reported functionalized alginate nanoparticles loaded with rifampicin (RIF) and the antioxidant ascorbic acid (ASC) with CS and the nonionic surfactant T80, thus providing a hydrophilic protective layer through the "sugar cluster effect" (Figure 2a). Experimental data have shown that nanoparticles loaded with RIF/ASC are mucus inert and can penetrate the mucus layer of the respiratory tract (Figure 2b) and become internalized.…”