An intelligent multicompartmental system based on thermo-sensitive starch microspheres for temperature-controlled release of drugs

Gheorghe Fundueanu, Marieta Constantin, Paolo Ascenzi, Bogdan C. Simionescu

Research output: Contribution to journalArticlepeer-review

Abstract

An original multicompartmental drug delivery system based on encapsulation of "intelligent" starch microspheres was designed and developed. Starch microspheres with thermo-responsive properties and possessing strong anionic functional groups (-SO3H), capable to bind electrostatically drugs, has been prepared. Firstly, the thermo-responsive units based on copolymer of poly(N-isopropylacrylamide-co-N,Ndimethylacrylamide) with a lower critical solution temperature around 36°C, were grafted on preformed starch microspheres. Secondly, the strong anionic groups (-SO3H) were introduced by sequential grafting of 2-acrylamido-2-methyl-1-propanesulfonic acid on the remaining-OH groups of starch. The thermo-sensitive microspheres with sulfonic groups display a sharp phase transition around the human body temperature. They were complexed with the positively-charged metoclopramide (low molecular weight model drug) and then encapsulated in cellulose acetate butyrate microcapsules by an oil-in-water solvent evaporation method. The swelling and diffusion of encapsulated microspheres to the aqueous continuous phase is avoided because the temperature of aqueous phase is higher than volume phase transition temperature (VPTT) of microspheres. This multicompartmental device could develop the background of "smart" implantable drug delivery system for persons that work in dangerous cold places (builders, climbers). When the temperature of the human body decreases below the normal temperature (the threshold temperature could be tuned), the encapsulated microspheres swell extensively in contact with physiological fluids, break the microcapsules and a large amount of bioactive compounds is released, keeping the activity of the vital organs. In normal physiological conditions (above LCST), the microspheres slightly swell, fill up the microcavities of microcapsules, but do not break them and release the drug in microcompartments. These microcompartments become microreservoirs with bioactive compounds and release it with a very low rate maintaining the necessary concentration for a sustained activity of the body.

Original languageEnglish
Pages (from-to)693-704
Number of pages12
JournalBiomedical Microdevices
Volume12
Issue number4
DOIs
Publication statusPublished - Aug 2010

Keywords

  • Drug delivery systems
  • Intelligent microspheres
  • Multicompartmental systems
  • Stimuli-sensitive polymers
  • Volume phase transition temperature

ASJC Scopus subject areas

  • Biomedical Engineering
  • Molecular Biology

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