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.
Highlights
Polymeric nanoparticles are one of the most explored carriers for mucosal and transmucosal delivery of biopharmaceuticals
One sole research group reported their use in mucosal protein delivery [11,21], focusing an application in oral administration and using fluorescein isothiocyanate bovine serum albumin (FITC-BSA) as model protein
Chitosan/chondroitin sulfate (CS/CHS) nanoparticles were successfully obtained by a process of polyelectrolyte complexation
Summary
Polymeric nanoparticles are one of the most explored carriers for mucosal and transmucosal delivery of biopharmaceuticals. Nanoparticulate systems might provide drug protection from aggressive environmental conditions [1,2] and potentiate increased drug absorption by reducing epithelial resistance to transport [3,4] Natural polymers such as chitosan (CS) and chondroitin sulfate (CHS) have been frequently used as matrix materials in drug delivery systems. CHS is a physiological sulfated glycosaminoglycan existing in the normal lung and other body structures [8,9] These polysaccharides have been reported to assemble into nanoparticles by a mild method of polyelectrolyte complexation [10,11], where the positively-charged amino groups of CS interact with the negatively-charged sulfate and carboxylate groups of CHS [1]. The fact that CHS is endogenous of the lung raises the interest of this polysaccharide for pulmonary and, generally, respiratory drug delivery applications
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