Indomethacin-loaded polymer nanocarriers based on poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5) undecane): preparation, in vitro and in vivo evaluation

Abstract

The study is focused on the development of copolymers based on poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5]-undecane). The macromolecular compounds were synthesized by dispersion polymerization in the presence of the radical initiator 4,4'-azobis(cyanopentanoic acid) and using sodium lauryl sulfate as tensioactive compound and poly(aspartic acid) (PAS) as protective colloid. PAS presents biocompatibility and biodegradability, and assures the increase of the absorbent character for the new synthesized network, and also, can supplement the hydrogen bonds contributing to the stability of the achieved complexes. The prepared polymeric networks were characterized by FTIR, SEM, and thermogravimetric analyses. The dependence on the pH of the swelling degree equilibrium was also evaluated correlated also with different temperature values. The poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5]-undecane) copolymers were evaluated as matrix for indomethacin (INN) as model drug loaded onto these polymeric networks. The evaluation of the homogeneity distribution of the INN drug in polymeric network was made by near infrared chemical imaging (NIR-CI) and correspondingly statistical analysis. The pharmacokinetic profile was achieved performing the in vitro release of the INN drug from the polymeric network. The data resulted from the in vivo experimental studies, respectively the biocompatibility tests, somatic nociceptive experimental model (Tail flick test) and visceral nociceptive experimental model (Writhing test)-are also reported in the study.