Poly(2‐ethyl‐2‐oxazoline) grafted gellan gum for potential application in transmucosal drug delivery
Janni Lavikainen, Moldir Dauletbekova, Gaukhar Toleutay, M. Kaliva, Μaria Chatzinikolaidou, Sarkyt E. Kudaibergenov, А. В. Теньковцев, Vitaliy V. Khutoryanskiy, Maria Vamvakaki, Vladimir Aseyev
Abstract
Gellan gum (GG) has been used to prepare polymeric carriers with prolonged retention on the eye surface for topical ocular drug delivery. In this work, GG was chemically modified with short poly(2‐ethyl‐2‐oxazoline) (PEtOx) chains that were expected to have minimal adhesion to mucosal tissues (mucoadhesion). The choice of synthetic procedure, solvents, and reagents has been dictated by biocompatibility of the materials and possible application in drug delivery. The grafts were synthesized via cationic ring‐opening polymerization and their living chains were attached onto deprotonated gellan backbone. The derivatives with three degrees of grafting were prepared by varying the in‐feed mass ratio of PEtOx grafts over GG. NMR and FT‐IR spectroscopies, thermogravimetric analysis, and SEC evidenced that the grafting had actually taken place. However, a greater diffusion coefficient determined for the copolymer, using diffusion‐ordered spectroscopy (NMR), in relation to the diffusion of the unmodified GG, suggested either partial degradation of the backbone or a more compact structure of the copolymer. GG and its graft copolymers (GG‐g‐PEtOx) were found to be highly biocompatible with cells cultured under their induction at concentration of 1, 0.1 and 0.01 mg/mL demonstrated a physiological morphology, as well as an increase in viability and proliferation.