*2.1. Materials*

Nicotine was obtained from Sigma-Aldrich, St. Louis, MO, USA. The polymers employed for gelisphere preparation included sodium alginate (FMC BioPolymer, Drammen, Norway) and HEC (Hercules Inc., Natrosol® Pharm, Wilmington, DE, USA). The crosslinking reagents employed were calcium chloride (CaCl2) and barium chloride (BaCl2) (UniLab®, Saarchem (Pty) Ltd., Krugersdorp, South Africa). PLGA (Resomer® L503, Evonik Nutrition & Care GmbH, Essen, Germany), HPMC (Methocel ™ K4M, Dow Chemical Company, Pittsburg, CA, USA) and PEO (PolyoxTM WSR 303; Union Carbide, Bound Brook, NJ, USA) were employed as the external matrices.
