The research described here probed the thermodynamics and kinetics of Vitamin B12 release from two types of polymeric gel scaffolds for targeted drug delivery applications. The polymeric gel scaffolds were successfully prepared from sodium alginate and polyvinyl acetate (PVA) using crosslinking and casting mechanisms, respectively. Vitamin B12 was effectively blended into the polymeric gel scaffolds during their synthesis processes. The release of Vitamin B12 from the polymeric gel scaffolds was characterized by immersing the scaffolds in a brine solution at various temperatures (25 °C, 32 °C and 37 °C) and, simultaneously, the transient concentrations were measured using a UV visible spectrophotometer. The sodium alginate gel scaffolds exhibited a more rapid release of Vitamin B12 as compared to the PVA gel scaffolds. The Vitamin B12 release kinetics from the alginate and PVA scaffolds were characterized by fitting the experimental data with various diffusion kinetic models. The Vitamin B12 release from the alginate gel scaffolds followed the Peppas-Sahlin model, whereas releases from the PVA gel scaffolds were fitted to the Hopfenberg model. The diffusion coefficients for the alginate scaffolds with respect to the three temperatures were found to be 15.72 m2/s, 17.17 m2/s and 18.58 m2/s respectively whereas the diffusion coefficients for the PVA scaffolds with respect to the three temperatures were found to be 0.23 m2/s, 0.29 m2/s and 0.32 m2/s respectively. The activation energies (Ea) for the two types of polymeric scaffolds were calculated using the Stannett equation and found to be 10.38 kJ.mol−1 and 20.47 kJ.mol−1 for the alginate and PVA scaffolds, respectively, for all three temperatures. © 2020 Taylor & Francis Group, LLC.