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Site-Targeted Drug Delivery Systems: Polymeric Carriers01:24

Site-Targeted Drug Delivery Systems: Polymeric Carriers

Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...

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Evaluation of Polymeric Gene Delivery Nanoparticles by Nanoparticle Tracking Analysis and High-throughput Flow Cytometry
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Stabilized nanocarriers for plasmids based upon cross-linked poly(ethylene imine).

Michael Neu1, Johannes Sitterberg, Udo Bakowsky

  • 1Department of Pharmaceutics and Biopharmacy, Philipps Universität, 35037 Marburg, Germany.

Biomacromolecules
|December 13, 2006
PubMed
Summary

Stabilized poly(ethyleneimine)/DNA polyplexes were created using disulfide bonds. Cross-linking polyplexes after formation enhanced stability and reduced blood component interactions for in vivo applications.

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Gene Delivery

Background:

  • Poly(ethyleneimine) (PEI)/DNA polyplexes are crucial for gene delivery but often lack stability.
  • Improving polyplex stability and biocompatibility is essential for in vivo applications.

Purpose of the Study:

  • To develop stabilized PEI/DNA polyplexes using biodegradable disulfide cross-linking.
  • To evaluate the impact of cross-linking methods on polyplex characteristics and performance.

Main Methods:

  • Investigated PEI cross-linking with dithiobis(succinimidyl propionate) (DSP).
  • Assessed polyplex size and zeta potential using light scattering and microelectrophoresis.
  • Analyzed morphology and mechanical stability with atomic force microscopy (AFM).
  • Evaluated interactions with albumin, erythrocytes, and stability in high ionic strength and against polyanions.

Main Results:

  • Cross-linking polyplexes after complexation yielded small (100-300 nm) polyplexes with positive zeta potential using high molecular weight (HMW) PEI.
  • Cross-linking significantly enhanced resistance to polyanion exchange and high ionic strength.
  • AFM confirmed no morphological changes but showed increased mechanical stability in cross-linked HMW PEI polyplexes.
  • Cross-linked polyplexes exhibited reduced interactions with albumin and erythrocytes.

Conclusions:

  • Post-complexation cross-linking of PEI/DNA polyplexes enhances stability and biocompatibility.
  • These stabilized polyplexes are promising for in vivo gene delivery, offering redox-triggered activation potential.