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Development of chitosan coated calcium-alginate nanocapsules for oral delivery of liraglutide to diabetic patients

Fatemeh Shamekhi

 Increasing prevalence, variable pathogenesis and natural history of progressive type II diabetes, highlight the necessity of immediate development of new therapeutic strategies Glucagon-like peptide-1 receptor agonists are a new class of injectable antidiabetic drugs. Chitosan coated calcium-alginate nanocapsules were developed for oral sustained delivery of liraglutide, a long-acting analog of glucagon like peptid-1. The aim of such drug delivery system is to recover diabetic patient compliance which otherwise demands prolonged repeatedly injections. The effect of coating components including sodium alginate, calcium chloride and chitosan concentrations on the particle size was studied based on response surface methodology. The beads were characterized through dynamic light scattering (DLS), scanning and transmission electron microscopy (SEM and TEM) as well as fourier transform infrared spectroscopy (FTIR). It was shown that the diameter of the formed beads was most dependent on the encapsulation technique and alginate concentration. SEM revealed spherical and smooth particles of up to 100 nm diameter for optimum composition of alginate 0.5%, chitosan 0.5% and calcium chloride 0.5% in the ratio of 3:1:1. The resulting bead formulation had a loading efficiency of 92.5% and loading capacity of 54.16 %. In-vitro release studies in simulated gastrointestinal conditions were carried out in a sequential technique and the amount of drug release was found to be 39.1% after 8 hours. The MTT results of developed nanocarrier revealed up to 52.05% viability enhancement compared to free drug in 0.3 mg concentration. The results of this study demonstrated that chitosan coated calcium-alginate nanoparticles hold promise as a potential natural biodegradable polymer-based oral carrier of liraglutide for better management of diabetes.