Design and in vitro assessment of chitosan nanocapsules for the pulmonary delivery of rifabutin.

Tuberculosis (TB) is a life-threatening disease and a main cause of death worldwide. It mainly affects the lungs, and it is attributed to the infection with Mycobacterium tuberculosis (MTB). Current treatments consist of the oral administration of combinations of antibiotics including rifabutin, in high doses and for long periods of time. These therapeutic regimens are associated with many side effects and high rates of drug resistance. To overcome these problems, this study aims at developing a nanosystem for the improved delivery of antibiotics, with potential application in pulmonary delivery. Chitosan-based nanomaterials are widely used in biomedical applications, due to their biodegradability and biocompatibility, as well as their potential antimicrobial effects and lack of toxicity. In addition, this polymer is particularly attractive for mucosal delivery due to its bioadhesive properties. Therefore, the structure of the proposed nanocarrier consists of a chitosan shell and a lipid core with a combination of different oils and surfactants to allow optimal association of the hydrophobic drug rifabutin. These nanocapsules were characterized in terms of size, polydispersity index, surface charge, morphology, encapsulation efficiency and biological stability. The release kinetics of the drug-loaded nanostructures was evaluated in simulated lung media. Moreover, in vitro studies in different cell models (A549 and Raw 264.7 cells) demonstrated the safety of the nanocapsules as well as their efficient internalization. An antimicrobial susceptibility test was performed to evaluate the efficacy of the rifabutin-loaded nanocapsules against Mycobacterium phlei. This study indicated complete inhibition for antibiotic concentrations within the expected susceptibility range of Mycobacterium (≤ 0.25-16 mg/L).

Purification of Hollow Sporopollenin Microcapsules from Sunflower and Chamomile Pollen Grains.

Pollen grains are natural microcapsules comprised of the biopolymer sporopollenin. The uniformity and special tridimensional architecture of these sporopollenin structures confer them attractive properties such as high resistance and improved bioadhesion. However, natural pollen can be a source of allergens, hindering its biomedical applicability. Several methods have been developed to remove internal components and allergenic compounds, usually involving long and laborious processes, which often cannot be extended to other pollen types. In this work, we propose an abridged protocol to produce stable and pristine hollow pollen microcapsules, together with a complete physicochemical and morphological characterization of the intermediate and final products. The optimized procedure has been validated for different pollen samples, also producing sporopollenin microcapsules from Matricaria species for the first time. Pollen microcapsules obtained through this protocol presented low protein content (4.4%), preserved ornamented morphology with a nanoporous surface, and low product density (0.14 g/cm3). These features make them interesting candidates from a pharmaceutical perspective due to the versatility of this biomaterial as a drug delivery platform.