Development and characterization of inhalable hybrid nanostructured microparticles for lung infections treatment

ISLAN GA; CACICEDO ML; BOSIO VE; CASTRO GR

Lille

Simposio; 10th European Symposium on Biochemical Engineering Sciences and 6th International Forum on Industrial Bioprocesses; 2014

IFIB - ACS (USA), University of Liege, Institute Pascal

The objective of the present work is the development and characterization of nanostructured microparticles encapsulating Levofloxacin as a model drug for lung infectionstreatment. Microparticles were developed by co-precipitation of calcium carbonate in presence of biopolymers: alginate (Alg) or high methoxyl pectin (HMP). The obtained hybrid microparticles showed sizes from 3 to 5 micrometers, an ideal size for pulmonary delivery. Levofloxacin, a quinolones family antibiotic, was incorporated by absorption. CaCO3/Alg and CaCO3/Alg-HM hybrid microparticles showed a Levofloxacin encapsulation percentage of 13.5 and 7.3 % respectively. In order to raise the drug entrapped, a surface modification was carried out by incubation of microparticles with an Alginate Lyase (AL), an alginate hidrolase. After treatment, microspheres were observed by scanning electron microscopy (SEM). Images of CaCO3/Alg microspheres showed a rougher surface, while CaCO3/Alg-HMP ones exhibited some ?nano-balloon? patterns on surface. This directly impacted in an increase of the surface to volume ratio of microparticles. Once microspheres were treated and washed, incubation in a Levofloxacin solution (1mg/ml) resulted in a loading absorption percentage of 38 and 43 % respectively. CaCO3/Alg showed an in vitro controlled release of the drug after 24 hours, reaching the 100%. After AL treatment, microparticles showed a more sustained release, releasing the 60 % after 24 hours. By the other hand, CaCO3/Alg-HMP and AL treated CaCO3/Alg-HMP microparticles released a 23 and 49 % respectively after 24 hours in the same experimental conditions. Non-treated and treated microspheres were evaluated by Differential Scanning Calorimetry (DSC). Differences in a typicalendothermic peak at 90.6 and 90.3 ºC for CaCO3/Alg and CaCO3/Alg-HMP respectively were found when microparticles were AL treated. A reduction in these peakstemperature was observed, indicating a modification of the matrices structure. In addition, X-ray and ATR studies were carried out. Results suggesteda modification of the microparticles after enzymatic treatment.In conclusion, the developed nanostructured microparticles offer a new alternative to obtain surface modify carriers for drug delivery. Considering their size, the microparticles result optimums for inhalatory drug delivery. AL treatment enhances the specific surface of microparticles, resulting in an increase of drug loading and modification of the release patters. The present work demonstrates a significant progress in the developed of carriers for treatment of pulmonary infections.