Entrapment and release of drugs by a strict "on-off" mechanism in pullulan microspheres with pendant thermosensitive groups

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

Research output: Contribution to journalArticlepeer-review


Here, we report a new method to predict the appropriate size of drugs which can be entrapped in and released from a hydrogel with pendant thermosensitive units by a strict "on-off" mechanism. Moreover, the valve-type action of the thermosensitive arms has been investigated. Inverse size exclusion chromatography (ISEC) and environmental scanning electron microscopy (ESEM) have been used to characterize the extension and collapse of the pendant thermosensitive units, below and above the lower critical solution temperature (LCST) under physiological conditions, confirming the hypothesis postulated by the "arid" theoretical models.The functionalized pullulan (Pul) microspheres, here prepared, were coupled with thermoresponsive oligomers by reaction between the -NH2 end-group of oligomers and chlorine present on Pul microspheres. The Pul microspheres with temperature sensitive moieties were packed in a glass column and the elution volume of standard molecule with well-known molecular weights (radius of gyration) was determined below and above the LCST. FITC-Dextran 4000 diffused through the pores of Pul microspheres with short thermosensitive arms (Mw = 1500 g/mol) both below and above the LCST of the thermosensitive units. In contrast, Pul microspheres with long thermosensitive arms (Mw = 3300 g/mol) allowed the diffusion of FITC-Dextran 4000 only above the LCST of the thermosensitive units. Indeed, the long thermosensitive arms are extended below the LCST and FITC-Dextran 4000 is completely excluded from the pores. The loading/release profile of this model molecule follows an "on-off" mechanism, confirming the results obtained by ISEC. ESEM was used as a new technique, taking images of the surface of the thermosensitive pullulan microspheres in their natural swollen state, with no prior specimen preparation, below and above the LCST. The low toxicity of pullulan microspheres observed below and above the LCST of thermosensitive units at high concentrations (10 mg/ml) recommends their potential use for controlled drug delivery applications.

Original languageEnglish
Pages (from-to)9544-9553
Number of pages10
Issue number36
Publication statusPublished - Dec 2010


  • " on-off" release mechanism
  • Drug delivery
  • Pullulan
  • Thermoresponsive polymers

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics


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