Toxicological evaluation of lactose and chitosan delivered by inhalation

Abstract

Abstract-These days, inhalation constitutes a promising administration route for many drugs. However, this route exhibits unique limitations, and formulations aimed at pulmonary delivery should include as few as possible additives in order to maintain lung functionality. The purpose of this work was to investigate the safety of lactose and chitosan to the pulmonary tissue when delivered by inhalation. The study was carried out with 18 Wistar rats divided in three groups receiving distilled water, lactose or chitosan. A solution of each excipient was administered by inhalation at a dose of 20 mg. The lungs were excised and processed to determine several biochemical parameters used as toxicity biomarkers. Protein and carbonyl group content, lipid peroxidation, reduced and oxidized glutathione (GSSG), myeloperoxidase (MPO), cooper/zinc and manganese superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were determined. Results of myeloperoxidase activity and glutathione disulfide lung concentrations showed a relevant decrease for chitosan group compared to control: 4.67 ± 2.27 versus 15.10 ± 7.27 (P = 0.011) for MPO and 0.89 ± 0.68 versus 2.02 ± 0.22 (P = 0.014) for GSSG. The other parameters did not vary significantly among groups. Lactose and chitosan administered by inhalation failed to show toxic effects to the pulmonary tissue. A protective effect against oxidative stress might even be attributed to chitosan, since some biomarkers had values significantly lower than those observed in the control group when this product was inhaled. Nevertheless, caution must be taken regarding chemical composition and technological processes applied to incorporate these products during drug formulation, in particular for dry powder inhalators.

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