PH- and temperature-sensitive polymeric microspheres for drug delivery: The dissolution of copolymers modulates drug release

Gheorghe Fundueanu, Marieta Constantin, Cristina Stanciu, Georgios Theodoridis, Paolo Ascenzi

Research output: Contribution to journalArticlepeer-review


Most pH-/temperature-responsive polymers for controlled release of drugs are used as cross-linked hydrogels. However, the solubility properties of the linear polymers below and above the lower critical solution temperature (LCST) are not exploited. Here, the preparation and characterization of poly (N-isopropylacrylamide-co-methacrylic acid-co-methyl methacrylate) (poly (NIPAAm-co-MA-co-MM)) and poly (N-isopropylacrylamide-co-acrylamide) (poly (NIPAAm-co-AAm)), known as "smart" polymers (SP), is reported. Both poly (NIPAAm-co-MA-co-MM) and poly (NIPAAm-co-AAm) display pH- and temperature-responsive properties. Poly (NIPAAm-co-MA-co-MM) was designed to be insoluble in the gastric fluid (pH = 1.2), but soluble in the intestinal fluid (pH = 6.8 and 7.4), at the body temperature (37°C). Poly (NIPAAm-co-AAm) was designed to have a lower critical solution temperature (LCST) corresponding to 37°C at pH = 7.4, therefore it is not soluble above the LCST. The solubility characteristics of these copolymers were exploited to modulate the rate of release of drugs by changing pH and/or temperature. These copolymers were solubilized with hydrophobic cellulose acetate butyrate (CAB) and vitamin B 12 (taken as a water soluble drug model system) in an acetone/methanol mixture and dispersed in mineral oil. By a progressive evaporation of the solvent, the liquid droplets were transformed into loaded CAB/SP microspheres. Differential scanning calorimetric studies and scanning electron microscopy analysis demonstrated that the polymeric components of the microspheres precipitated separately during solvent evaporation forming small microdomains. Moreover, vitamin B12 was found to be molecularly dispersed in both microdomains with no specific affinity for any polymeric component of microspheres. The release of vitamin B12 was investigated as a function of temperature, pH, and the CAB/SP ratio.

Original languageEnglish
Pages (from-to)2465-2475
Number of pages11
JournalJournal of Materials Science: Materials in Medicine
Issue number12
Publication statusPublished - Dec 2009

ASJC Scopus subject areas

  • Biophysics
  • Biomaterials
  • Bioengineering
  • Biomedical Engineering


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