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Modulation of Polyplex Release from Biodegradable Microparticles through Poly(ethylenimine) Modification and Varying Loading Concentration

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ABSTRACT

Purpose

This work investigates the effects of hyaluronic acid (HA) conjugated onto branched poly(ethylenimine) (bPEI) and varying loading concentrations of these polymers complexed with DNA on their release from poly(DL-lactic-co-glycolic acid) (PLGA) microparticles and the transfection of target cells.

Methods

To examine the effect of alteration of the gene delivery polymer on the system, we observed the morphology, size, loading efficiency, polymer and DNA release, and the transfection efficiency for the microparticles formed with three internal phase loading concentrations during microparticle formation.

Results

Addition of HA to this vector allowed for increased loading concentration within these systems and significantly altered release kinetics without changing the morphology of the particles. The incorporation of HA onto the bPEI backbone significantly increased the transfection efficiency of the complexes released from the corresponding microparticle formulation.

Conclusions

The results show that the modification of bPEI with HA and the concentration of loaded polymer/DNA complexes can significantly alter the entrapment and release profiles from PLGA microparticles. This is significant in that it offers insight into the effects of modification of gene delivery vectors on a controlled release system designed to achieve a sustained therapeutic response.

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ACKNOWLEDGMENTS AND DISCLOSURES

We acknowledge support from the National Institutes of Health (R21 AR56076 and R01 AR57083). We would like to thank Patrick Spicer and Allan Henslee for their guidance on the project.

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Authors and Affiliations

  1. Department of Bioengineering, Rice University, 6500 Main St, Houston, Texas, 77030, USA

    Clark J. Needham, Sarita R. Shah, Paschalia M. Mountziaris, F. Kurtis Kasper & Antonios G. Mikos

  2. Department of Bioengineering, Rice University, MS-142, P.O. Box 1892, Houston, Texas, 77251-1892, USA

    Antonios G. Mikos

Authors
  1. Clark J. Needham
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  2. Sarita R. Shah
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  3. Paschalia M. Mountziaris
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  4. F. Kurtis Kasper
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  5. Antonios G. Mikos
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Correspondence to Antonios G. Mikos.

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Needham, C.J., Shah, S.R., Mountziaris, P.M. et al. Modulation of Polyplex Release from Biodegradable Microparticles through Poly(ethylenimine) Modification and Varying Loading Concentration. Pharm Res 31, 77–85 (2014). https://doi.org/10.1007/s11095-013-1133-1

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  • DOI: https://doi.org/10.1007/s11095-013-1133-1

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