Development of Epinephrine Nanoparticles Using Chitosan for the Treatment of Anaphylaxis

Purpose. Epinephrine was previously formulated into fast-disintegrating sublingual tablets (AAPS PharmSciTech. 2006;7(2): Article 41) and the sublingual bioavailability was established in vivo (J Allergy Clin Immunol 2006;117(2):398-403) for the potential first-aid treatment of anaphylaxis. The purpose of this study was to develop and characterize epinephrine nanoparticles to enhance the sublingual bioavailability of epinephrine. Methods. Epinephrine bitartrate equivalent to epinephrine 10%, 20%, 30% and 40% were loaded into chitosan nanoparticles using ionic gelation method. Chitosan to tripolyphosphate (TPP) weight ratio was studied at 2:1, 3:1, 4:1, 5:1 and 6:1. Particle size and zeta potential were measured after nanoparticles fabrication using Zetasizer. Samples were centrifuged and supernatant was analyzed using HPLC to determine the encapsulation efficiency. Results. Nanoparticles in the size range of 100-400 nm were obtained using 2:1 and 3:1 weight ratios of chitosan to TPP. Zeta potential was increased with the increase chitosan weight ratio, and decreased with the increase in epinephrine load %. Encapsulation efficiency was increased by increasing weight ratio of chitosan; but resulted in lower encapsulation efficiency at epinephrine 40%. Conclusion. By adjusting the chitosan 31 weight ratio, optimum size of epinephrine nanoparticles can be obtained. Encapsulation efficiency of epinephrine into chitosan nanoparticles depends on weight ratio of chitosan and epinephrine load %