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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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Bioreducible polyether-based pDNA ternary polyplexes: balancing particle stability and transfection efficiency.

Tsz Chung Lai1, Kazunori Kataoka, Glen S Kwon

  • 1Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin - Madison, 777 Highland Avenue, Madison, WI 53705-2222, USA.

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New ternary polyplexes improve gene delivery stability and efficiency. Reducible polyplexes offer enhanced transfection by triggered release, maintaining particle stability for effective plasmid DNA delivery.

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Area of Science:

  • Biomaterials Science
  • Gene Delivery Systems
  • Nanotechnology

Background:

  • Plasmid DNA (pDNA) complexed with block copolymers forms polyplexes for gene delivery.
  • Existing polyplexes face challenges with colloidal stability and transfection efficiency.
  • Pluronic P85-block-poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (P85-b-P[Asp(DET)]) shows high transfection but poor stability.

Purpose of the Study:

  • To develop stable ternary polyplexes for enhanced gene delivery using pDNA.
  • To investigate the role of bioreducible P(EPE)-SS-P[Asp(DET)] in improving transfection efficiency.
  • To maintain adequate transfection while addressing the stability issues of P85-b-P[Asp(DET)]-based polyplexes.

Main Methods:

  • Preparation of ternary polyplexes using PEG-based block cationomer, P(EPE)-b-P[Asp(DET)], and pDNA.
  • Utilized a bioreducible P(EPE)-SS-P[Asp(DET)] as a substitute to assess triggered polymer release.
  • Evaluated polyplex stability against salt-induced aggregation and assessed gene delivery ability.

Main Results:

  • Ternary polyplexes demonstrated improved stability against salt-induced aggregation compared to binary complexes.
  • Gene delivery efficiency decreased with increasing amounts of PEG-b-P[Asp(DET)] in complexation.
  • Reducible ternary complexes achieved higher transfection than non-reducible ones due to triggered release.

Conclusions:

  • Reducible ternary polyplexes offer enhanced transfection efficiency through triggered release mechanisms.
  • These reducible polyplexes maintain comparable colloidal stability to non-reducible counterparts.
  • The developed reducible ternary complexes provide a promising strategy for effective gene delivery without compromising particle stability.