Thermo-sensitive gellan maleate/N-isopropylacrylamide hydrogels: initial “in vitro” and “in vivo” evaluation as ocular inserts

  • Mihaela Hamcerencu
  • Jacques DesbrieresEmail author
  • Marcel PopaEmail author
  • Gérard Riess
Original Paper


Hydrogels are among the most used polymer–drug systems, polysaccharide-based materials presenting many advantages to be used for controlled release applications. Gellan maleate/NIPAm hydrogels are hydrophilic swelling matrixes that were originally developed for biomedical applications as controlled release dosage forms. The purpose of this study is to explore the ability of gellan maleate/NIPAm thermoreversible hydrogels for ophthalmic applications as ocular inserts. Studied hydrogels were synthesized by free radical grafting/polymerization of unsaturated esters (gellan maleate) with N-isopropylacrylamide (NIPAm) and N,N′-methylenebisacrylamide as cross-linker. They are evaluated for swelling degree, in vitro inclusion and release of drugs (adrenaline and chloramphenicol) and in vivo biocompatibility. The hydrogel is shown to be a temperature-responsive material with a LCST close to 36 °C. The swelling properties and the release of biologically active compounds occur when polymer conformation changes determining phase transition at LCST. Gellan-based hydrogels present reproducible responses to alternation between ambient temperature and human body one. The stability and biocompatibility were evaluated in vitro and in vivo. Tissue response to implantation of hydrogel was determined by histological analysis (haematoxylin–eosin–methylene blue and periodic acid–Schiff). A thin fibrous capsule was observed around the implanted hydrogels. No necrosis, calcification and acute inflammatory reaction were noted. Successful preliminary results were obtained for ophthalmic applications.


Hydrogels Gellan N-Isopropylacrylamide (NIPAm) Ocular inserts Temperature sensitive Ophthalmic applications 



The authors would like to thank the Agence Universitaire de la Francophonie (AUF), for financial support. Prof. Dr. Corneliu Cotea from Ion Ionescu de la Brad University of Agricultural Sciences and Veterinary Medicine of Iași is acknowledged for biocompatibility experiments.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Faculty of Chemical Engineering and Environment Protection“Gheorghe Asachi” Technical UniversityIasiRomania
  2. 2.Institut des Sciences Analytiques et de Physico-Chimie pour l’Environnement et les Matériaux (IPREM/EPCP), UMR CNRS 5254Université de Pau et des Pays de l’AdourPau Cedex 09France
  3. 3.Laboratoire de Photochimie et d’Ingénierie Macromoléculaire - Ecole Nationale de Chimie de MulhouseUniversité de Haute AlsaceMulhouse CedexFrance
  4. 4.Academy of Romanian ScientistsBucharestRomania

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