Desenvolvimento tecnológico e avaliação in vitro de nanocápsulas poliméricas contendo clorexidina com aplicação na prevenção de infecções respiratórias

Abstract

In patients admitted to the intensive care unit (ICU), the use of the orotracheal tube guarantees hemodynamic stability, however it facilitates the adhesion of microorganisms in oral tissues, favoring the development of pneumonia. To control the formation of biofilms, oral hygiene with the use of antiseptic is essentialIn order to prevent respiratory infections, the aim of this study was to develop andto evaluate suspensions of nanocapsules containing chlorhexidine optained by the interfacial deposition method of the preformed polymer using Eudragit® RS 100. The analytical method by high performance liquid chromatography (UHPLC) was developed and validated for the quantification of the chlorhexidine into the nanocapsules. The formulations presented encapsulation efficiency values higher than 99%. The obtained nanocapsules presented pH value of 6.8 with average particle size less than 150 nm and zeta potential of +22.4 mV. The images obtained by scanning electron microscopy revealed spherical, shape and smooth surface and homogeneity of the nanocapsules. Fourier transform infrared spectroscopy showed that there were no chemical reactions between the drug and the polymer. The results obtained by X-ray diffraction and differential scanning calorimetry revealed the absence of drug crystallinity of the loated nanocapsules, which confirmed its amorphous character, comparing to the polymer and the drug. The formulations presented acceptable stability parameters after 60 days of storage. The antimicrobial activity of chlorhexidine loaded nanocapsules was evaluated against: Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumoniae (sensitive strain), Klebsiella pneumoniae (resistant strain -extended-spectrum B-lactamase-producing), Staphylococcus aureus and Candida albicans and these results demonstrated that the chlorhexidine loaded nanosystem rept its antibacterial activity. The acute toxicity test using Artemia salina showed no lethality (LC50 of 1483.4 μg/mL) which indicated no toxicity. In vitro cell culture studies using 3T3 lines showed that the analyzed concentrations, the formulations developed showed no cytotoxic potential. The results suggest that the use of chlorhexidine nanoparticles may be a promising strategy in the prevention of respiratory system infections in the hospital. However, more preclinical and clinical trials are required.