Biocompatibility and Stability of Polysaccharide Polyelectrolyte Complexes Aimed at Respiratory Delivery

Abstract

Chitosan (CS) and chondroitin sulfate (CHS) are natural polymers with demonstrated applicability in drug delivery, while nanoparticles are one of the most explored carriers for transmucosal delivery of biopharmaceuticals. In this work we have prepared CS/CHS nanoparticles and associated for the first time the therapeutic protein insulin. Fluorescein isothiocyanate bovine serum albumin (FITC-BSA) was also used to enable comparison of behaviors regarding differences in molecular weight (5.7 kDa versus 67 kDa). Nanoparticles of approximately 200 nm and positive zeta potential around +20 mV were obtained. These parameters remained stable for up to 1 month at 4 °C. Proteins were associated with efficiencies of more than 50%. The release of FITC-BSA in PBS pH 7.4 was more sustained (50% in 24 h) than that of insulin (85% in 24 h). The biocompatibility of nanoparticles was tested in Calu-3 and A549 cells by means of three different assays. The metabolic assay MTT, the determination of lactate dehydrogenase release, and the quantification of the inflammatory response generated by cell exposure to nanoparticles have indicated an absence of overt toxicity. Overall, the results suggest good indications on the application of CS/CHS nanoparticles in respiratory transmucosal protein delivery, but the set of assays should be widened to clarify obtained results.

Chitosan/sulfated locust bean gum nanoparticles: In vitro and in vivo evaluation towards an application in oral immunization

“…However, on reaching −/+ charge ratios of 0.98, 1.06 and 1.21 precipitation occurred (CS/LBGS nanoparticles 1:3.25 to 1:4; w/w). Although this behavior was unexpected, it has been reported in other works regarding polysaccharide nanoparticles produced by the same methodology [32][33][34][35][36].…”

Hydrothermal Processing of Laminaria ochroleuca for the Production of Crude Extracts Used to Formulate Polymeric Nanoparticles

“…Complementarily to the evaluation of mitochondrial activity, the determination of the effect of exposure to extracts on the integrity of the cell membrane was further investigated as another indicator of toxicity. To do so, the release of the cytoplasmic enzyme lactate dehydrogenase (LDH) was quantified [38,39]. The extracts obtained from L. ochroleuca at different temperatures were tested at the two highest concentrations used in the MTT assay, 0.5 and 1.0 mg/mL, and exposure of HCT-116 cells for 24 h and 48 h ( Figure 6).…”

Recent Advances and Future Prospects of Non-Invasive Insulin Delivery Systems

“…By adding natural polymers like chitosan (CS) and chondroitin (CHS) 'CS/CHS nanoparticles' it is believed that the delivery of macromolecules through the lungs would improve. One study investigated the capacity of CS/CHS nanoparticles to release insulin for the respiratory delivery [39]. The results indicated the suitability of this application as the formulations remained stable at 4 °C for one month and had good insulin release, but further studies would be needed to establish the real potential of their application.…”