Prediction of the appropriate size of drug molecules that could be released by a pulsatile mechanism from pH/thermoresponsive microspheres obtained from preformed polymers

Gheorghe Fundueanu, Marieta Constantin, Ionela Oanea, Valeria Harabagiu, Paolo Ascenzi, Bogdan C. Simionescu

Research output: Contribution to journalArticlepeer-review

Abstract

Preparation of cross-linked pH/thermoresponsive microspheres from preformed polymers is still lacking in literature since copolymers possessing both temperature- and pH-sensitive units together with a cross-linkable moiety in appropriate ratios are required. Moreover, choosing of the appropriate drugs able to be loaded and then released in a pulsatile manner is randomly performed. Here, we report the synthesis of pH/thermoresponsive cross-linked microspheres based on N-isopropylacrylamide and N-alloc-ethylenediamine. A chromatographic method was developed to predict the appropriate size of drug molecules that could be loaded and then released in a pulsatile manner. Accordingly, it was established that common drugs (salicylic acid, benzoic acid, nicotinic acid, lidocaine and diclofenac), with molecular weights ranging between 100 and 1000 g mol-1, could be loaded and released in a pulsatile manner. Biologic molecules with higher molecular weights (heparin, lysozyme and bovine serum albumin) are completely excluded from the pores of cross-linked pH/thermoresponsive microspheres both below and above the volume phase transition temperature.

Original languageEnglish
Pages (from-to)1281-1289
Number of pages9
JournalActa Biomaterialia
Volume8
Issue number3
DOIs
Publication statusPublished - Mar 2012

Keywords

  • Drug delivery system
  • Inverse size exclusion chromatography
  • Lower critical solution temperature
  • pH/thermoresponsive copolymers
  • Smart polymers

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Biotechnology
  • Biochemistry
  • Molecular Biology

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