New Grafted Copolymers Carrying Betaine Units Based on Gellan and N-Vinylimidazole as Precursors for Design of Drug Delivery Systems

Abstract

New grafted copolymers possessing structural units of 1-vinyl-3-(1-carboxymethyl) imidazolium betaine were obtained by graft copolymerization of N-vinylimidazole onto gellan gum followed by the polymer-analogous reactions on grafted polymer with the highest grafting percentage using sodium chloroacetate as the betainization agent. The grafted copolymers were prepared using ammonium persulfate/N,N,N′,N′ tetramethylethylenediamine in a nitrogen atmosphere. The grafting reaction conditions were optimized by changing one of the following reaction parameters: initiator concentration, monomer concentration, polymer concentration, reaction time or temperature, while the other parameters remained constant. The highest grafting yield was obtained under the following reaction conditions: ci = 0.08 mol/L, cm = 0.8 mol/L, cp = 8 g/L, tr = 4 h and T = 50 °C. The kinetics of the graft copolymerization of N-vinylimidazole onto gellan was discussed and a suitable reaction mechanism was proposed. The evidence of the grafting reaction was confirmed through FTIR spectroscopy, X-ray diffraction, 1H-NMR spectroscopy and scanning electron microscopy. The grafted copolymer with betaine structure was obtained by a nucleophilic substitution reaction where the betainization agent was sodium chloroacetate. Preliminary results prove the ability of the grafted copolymers to bind amphoteric drugs (cefotaxime) and, therefore, the possibility of developing the new sustained drug release systems.

Polybetaines in Biomedical Applications

“…A new sustained drug release system based on graft copolymers with a betaine structure has been synthesized from gellan and N-vinylimidazole [121]. Graft copolymers with betaine structure were obtained by a two-step reaction (Figure 5).…”

“…In vitro cefotaxime sodium salts (CF) release studies demonstrated the ability of the new graft copolymers to immobilize amphoteric drugs. It was also revealed that the mechanism of CF release from PG and PGB1 samples was controlled by the diffusion process or a combination of diffusion and swelling processes [121].…”

“…Another study was directed towards microparticles based on complexes between chitosan and two poly(N-vinylimidazole)-based polycarboxybetaines that were synthesized In vitro cefotaxime sodium salts (CF) release studies demonstrated the ability of the new graft copolymers to immobilize amphoteric drugs. It was also revealed that the mechanism of CF release from PG and PGB1 samples was controlled by the diffusion process or a combination of diffusion and swelling processes [121].…”

Immobilization and Release Studies of Triazole Derivatives from Grafted Copolymer Based on Gellan-Carrying Betaine Units

“…Also, the choice of macromolecular support for immobilization of bioactive compounds is very important. Encouraged by the preliminary results obtained in our previous study [ 42 ], we chose to use for the immobilization of these new bioactive compounds two types of macromolecular supports: grafted copolymers and grafted copolymers carrying betaine units based on gellan and N-vinylimidazole (PG and PGB1, respectively). The structure of PG and PGB1 copolymers are presented in Figure 1 .…”

Design of new zwitterionic microparticles with intrinsic antibacterial activity

“…[9][10][11] Also, its tertiary nitrogen atom can participate in substitution or addition reactions with different betainizing agents, resulting in the preparation of polymers with betaine structure. 12,13 Polybetaines have been distinguished in their biocompatibility, hydrophilicity, antibacterial and antifouling properties. [14][15][16] The great diversity of polybetaines is due to several factors: the type of the anionic groups (carboxylate, sulfonate, or phosphate/phosphinate/phosphonate), the different lengths of the alkyl chain that separates the two ionic groups, and the chemical structure of monomers or polymers used in the synthesis of polybetaines.…”