Maleimide-functionalised PLGA-PEG nanoparticles as mucoadhesive carriers for intravesical drug delivery

Daulet B Kaldybekov1, Sergey K Filippov2, Aurel Radulescu3

  • 1School of Pharmacy, University of Reading, Whiteknights, RG6 6AD Reading, United Kingdom; Department of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, 050040 Almaty, Kazakhstan.

Insights

New mucoadhesive nanoparticles improve intravesical drug delivery for bladder cancer. Poly(lactide-co-glycolide)-block-poly(ethylene glycol)-maleimide (PLGA-PEG-Mal) nanoparticles show enhanced retention on bladder tissue, overcoming key limitations of current treatments.

Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Drug Delivery

Background:

  • Intravesical chemotherapy for bladder cancer faces limitations like poor drug retention and epithelial permeability.
  • Developing effective drug delivery systems is crucial to enhance treatment efficacy and reduce systemic side effects.

Purpose of the Study:

  • To develop and characterize maleimide-functionalized poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG-Mal) nanoparticles for enhanced mucoadhesive drug delivery to the urinary bladder.
  • To evaluate the in vitro retention and biocompatibility of these novel nanoparticles.

Main Methods:

  • Nanoparticles were synthesized and characterized using dynamic light scattering, transmission electron microscopy, and small-angle neutron scattering.
  • Mucoadhesion and retention were assessed using a flow-through fluorescence technique and the Wash Out50 (WO50) method on excised lamb bladder mucosa.
  • Biocompatibility was evaluated using the slug mucosal irritation test.

Main Results:

  • PLGA-PEG-Mal nanoparticle size was influenced by solvent and PEG molecular weight.
  • Maleimide-functionalized nanoparticles demonstrated significantly greater retention on bladder mucosa (WO50 = 15 mL) compared to maleimide-free nanoparticles (WO50 = 5 mL).
  • PEG-Mal materials exhibited non-irritant properties in the slug mucosal irritation test.

Conclusions:

  • PLGA-PEG-Mal nanoparticles represent a promising mucoadhesive formulation for improving intravesical drug delivery in bladder cancer treatment.
  • These nanoparticles effectively enhance drug retention within the urinary bladder, addressing a key challenge in current therapies.
  • The developed nanoparticles are biocompatible and non-irritant, suggesting their potential for safe clinical application.

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