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Rate-programmed drug delivery systems release drugs in a controlled manner to maintain therapeutic levels. Three main designs include reservoir, matrix, and hybrid systems.Reservoir systems consist of a drug core enclosed within a membrane that controls drug release. In non-swelling reservoir systems, polymers like ethyl cellulose or polymethacrylates are used. These do not hydrate in aqueous media and control release through membrane thickness, porosity, or insolubility. This type includes...
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Microwave-assisted Functionalization of Polyethylene glycol and On-resin Peptides for Use in Chain Polymerizations and Hydrogel Formation
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Engineered zero-order drug release from degradable PEG hydrogels - A rapamycin case study.

Lage Ahrenstedt1, Anel Oosthuysen1, Peter Zilla1

  • 1Cardiovascular Research Unit, University of Cape Town, Cape Town, South Africa.

Journal of Biomaterials Applications
|January 6, 2026
PubMed
Summary
This summary is machine-generated.

Researchers modified Rapamycin (Ra) for controlled drug delivery, creating hydrogels that release Ra over 7-19 days. Structural changes near the linker significantly impacted release rates, offering insights for advanced drug delivery systems.

Keywords:
PEGylationdrug deliveryhydrogelsrapamycinrelease kineticszero-order elution

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Area of Science:

  • Biomaterials Science
  • Polymer Chemistry
  • Drug Delivery

Background:

  • Controlled drug release systems are crucial for therapeutic efficacy.
  • Rapamycin (Ra) is a potent immunosuppressant with a narrow therapeutic window.
  • Hydrogel-based drug delivery offers potential for sustained release.

Purpose of the Study:

  • To synthesize and characterize Rapamycin-conjugated hydrogels for controlled drug release.
  • To investigate the impact of thioether ester linker structure on drug release kinetics.
  • To explore hydrogel architecture effects on Rapamycin elution profiles.

Main Methods:

  • Derivatization of Rapamycin with acryloyl chloride and iodoacetic acid.
  • Conjugation of modified Rapamycin to thiolated polyethylene glycols (PEGs).
  • Hydrogel formation via conjugate addition using multi-arm PEG macromers and thiolated PEG crosslinkers.
  • In vitro drug release studies under physiological conditions.

Main Results:

  • Zero-order Rapamycin release observed over 7-19 days, tunable by hydrogel architecture.
  • α-thioether ester linkages showed faster hydrolysis and release (11-31% increase) compared to β-thioether esters.
  • Hydrogels promoting swelling and degradation (PEG acrylates) exhibited higher drug release rates.
  • Ra-based crosslinking resulted in biphasic release: initial zero-order followed by a burst phase.

Conclusions:

  • Hydrogel design, particularly the thioether ester linker structure, significantly modulates Rapamycin release kinetics.
  • Electron-withdrawing effects of the thioether group accelerate ester hydrolysis and drug release.
  • These findings provide a foundation for designing advanced hydrogels for tailored controlled drug delivery applications.