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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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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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Related Experiment Video

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Efficient pDNA Delivery Using Cationic 2-Hydroxypropyl-β-Cyclodextrin Pluronic-Based Polyrotaxanes.

Vivek Badwaik1, Yawo Mondjinou1, Aditya Kulkarni1

  • 1Department of Chemistry, Multi-Disciplinary Cancer Research Facility, Bindley Bioscience Center, 1203 W. State Street, West Lafayette, Indiana 47907, USA.

Macromolecular Bioscience
|August 11, 2015
PubMed
Summary

New cationic Pluronic-based polyrotaxanes (PR(+)) show enhanced pDNA delivery and transfection efficiency in cells. These novel PR(+) vectors offer potent, low-toxicity alternatives for pDNA-based therapeutics.

Keywords:
gene deliverypDNApolyrotaxanetransfectionβ-cyclodextrins

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Area of Science:

  • Biomaterials Science
  • Gene Delivery Systems
  • Nanotechnology

Background:

  • Developing effective and safe non-viral vectors for pDNA delivery is crucial for gene therapy.
  • Pluronic-based polyrotaxanes offer a promising scaffold for creating novel drug delivery systems.
  • Cyclodextrin inclusion complexes can enhance the properties of polymeric carriers.

Purpose of the Study:

  • To synthesize and characterize cationic Pluronic-based polyrotaxanes (PR(+)) threaded with 2-hydroxypropyl-β-cyclodextrin (HPCD).
  • To evaluate the efficiency of these PR(+) systems as pDNA delivery vectors in multiple cell lines.
  • To compare the performance and toxicity of PR(+) systems against commercial transfection standards.

Main Methods:

  • Synthesis of cationic Pluronic-based polyrotaxanes (PR(+)) using HPCD.
  • Complexation of pDNA with PR(+) and characterization of resulting complexes (size, charge, stability).
  • In vitro assessment of cellular uptake, pDNA transfection efficiency, and cytotoxicity in various cell lines.

Main Results:

  • All synthesized PR(+) formed stable, positively charged pDNA complexes with diameters < 250 nm.
  • PR(+):pDNA complexes demonstrated enhanced cellular uptake and pDNA transfection efficiencies compared to L2K and bPEI.
  • The charge density and threading efficiency of PR(+) significantly influenced complex properties and transfection efficacy, with comparable or lower toxicity.

Conclusions:

  • HPCD-threaded Pluronic-based polyrotaxanes (PR(+)) are effective non-viral vectors for pDNA delivery.
  • These PR(+) systems exhibit superior transfection performance and favorable toxicity profiles.
  • The findings suggest significant potential for HPCD: Pluronic PR(+) as advanced vectors for pDNA-based therapeutics.