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 Loredana E. Nita, Aurica P. Chiriac, Manuela T. Nistor, Liliana Tartau ‘‘Petru Poni’’ Institute of Macromolecular Chemistry, Gr .T. Popa University of Medicine and Pharmacy, Grigore Ghica Voda Alley No. 41-A, 700487 IASI, Romania Received 22 September 2011; revised 29 November 2011; accepted 22 December 2012 Published online 24 March 2012 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.32679 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 macro- molecular compounds were synthesized by dispersion poly- merization in the presence of the radical initiator 4,4 0 - azobis(cyanopentanoic acid) and using sodium lauryl sulfate as tensioactive compound and poly(aspartic acid) (PAS) as protective colloid. PAS presents biocompatibility and biode- gradability, and assures the increase of the absorbent charac- ter 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) copoly- mers were evaluated as matrix for indomethacin (INN) as model drug loaded onto these polymeric networks. The eval- uation 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, respec- tively the biocompatibility tests, somatic nociceptive experi- mental model (Tail flick test) and visceral nociceptive experimental model (Writhing test)—are also reported in the study. V C 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 1121–1133, 2012. Key Words: bioactive material, controlled release, drug deliv- ery/release, matrix, molecular imaging How to cite this article: Nita LE, Chiriac AP, Nistor MT, Tartau L. 2012. 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. J Biomed Mater Res Part B 2012:100B:1121–1133. INTRODUCTION Reports concerning 2-hydroxyethyl methacrylate (HEMA) homopolymerization in aqueous medium using radical ini- tiators, or different systems of initiation are growing during last time. 1–5 Incorporation of HEMA in different ratios in copolymers presents also, special interest by yielding com- pounds of varied properties including hydrophilic/hydro- phobic balance and hemocompatibility. 6,7 The poly(HEMA)(p(HEMA)) biocompatibility assures the future use for the preparation of various biomedical and pharmaceutical materials, for example, optical lenses, implants, drug delivery devices, support for enzyme immo- bilization, and so forth. Other studies had in view the improvement of the p(HEMA) properties as for example the mechanical properties, permeability, temperature responsive characteristics, and the degree of hydration or the extent of network swelling, to display more favorable biological responses. 8,9 Polymer networks from amphiphilic copoly- mers have been extensively used as drug carrier systems to enhance drug solubility, stability, and biopharmaceutical properties, as for example the permeability across mem- branes and permanence in blood circulation. 10,11 In this context, in previous studies polymeric com- pounds based on 2-hydroxyethyl methacrylate and 3,9- divinyl-2,4,8,10-tetraoxaspiro (5.5) undecane (U) acquired through radical polymerization in the presence of different radical initiators as well as surfactants and protective col- loids have been realized. 12,13 Both comonomers—HEMA and U—are able for network and gel formation capacity. The copolymers based on HEMA and U are biodegradable and biocompatible presenting as well binding properties. U offers to its products amphilicity, good oxidative and ther- mal stability, good films formers, and acid pH sensitivity. These aspects justify the interest in performing the HEMA-U Correspondence to: A. P. Chiriac; e-mail: achiriac1@yahoo.com Contract grant sponsor: European Social Fund – ‘‘Cristofor I. Simionescu’’ Postdoctoral Fellowship Programme; contract grant number: IDPOSDRU/89/1.5/S/ 55216 Contract grant sponsor: Sectoral Operational Programme Human Resources Development 2007–2013 V C 2012 WILEY PERIODICALS, INC. 1121