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Smart drug delivery system activated by specific biomolecules.

Marieta Constantin1, Sanda Bucatariu1, Paolo Ascenzi2

  • 1Department of Natural Polymers, Bioactive and Biocompatible Materials, "Petru Poni" Institute of Macromolecular Chemistry, 700487 Iassy, Romania.

Materials Science & Engineering. C, Materials for Biological Applications
|January 12, 2020
PubMed
Summary

Intelligent drug delivery systems release medication upon detecting disease biomarkers. A novel copolymer, poly(NIPAAm-co-APM), activates in response to specific biomolecules, enabling targeted therapeutic release.

Keywords:
Drug deliveryPoly(N-isopropylacrylamide)Smart polymerStimuli-sensitive polymerTriggering agent

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Area of Science:

  • Biomaterials Science
  • Polymer Chemistry
  • Drug Delivery Systems

Background:

  • The human body releases specific biomolecules (e.g., histamines, antibodies, nitric oxide) during various disease conditions.
  • Existing drug delivery systems often lack specificity, leading to suboptimal therapeutic outcomes.
  • There is a need for "intelligent" systems that can release therapeutic agents only in the presence of specific disease-related compounds.

Purpose of the Study:

  • To design and develop an "intelligent" drug delivery system capable of releasing therapeutic agents in response to specific bioactive compounds.
  • To synthesize and characterize a novel pH/temperature-sensitive copolymer, poly(N-isopropylacrylamide-co-N-(3-aminopropyl)methacrylamide)) (poly(NIPAAm-co-APM)).
  • To evaluate the responsiveness and biocompatibility of microgels synthesized from the developed copolymer.

Main Methods:

  • Synthesis of poly(NIPAAm-co-APM) copolymer.
  • Fabrication of microgels from the synthesized copolymer.
  • Investigation of copolymer properties under physiological conditions (pH 7.4, 36°C).
  • Assessment of microgel response to specific biomolecules, including drug expulsion.
  • MTT assays to evaluate the cytotoxicity of the poly(NIPAAm-co-APM) microspheres.

Main Results:

  • The synthesized poly(NIPAAm-co-APM) copolymer exhibits tunable pH and temperature sensitivity.
  • Under normal physiological conditions, the microgels remain in an "inactivated" state.
  • Upon electrostatic interaction with specific biomolecules, the microgels undergo "activation", shrinking and expelling encapsulated drugs.
  • MTT tests confirmed that the poly(NIPAAm-co-APM) microspheres are non-toxic.
  • Rabbit dermal fibroblasts demonstrated excellent adhesion to the microsphere surface, indicating good biocompatibility.

Conclusions:

  • The developed poly(NIPAAm-co-APM) copolymer forms "intelligent" microgels that act as biosensors and drug delivery actuators.
  • These microgels can selectively release therapeutic agents upon encountering specific biomolecules, offering a targeted drug delivery approach.
  • The non-toxic and biocompatible nature of the microspheres supports their potential application in biomedical fields.