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Nanoparticles in thermosensitive gel based composite nanosystem for ocular diseases

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Abstract

The pentablock (PB) copolymers based composite nanosystems were designed to provide a long-term delivery of macromolecules to the back of the eye. A unique arrangement of each block (polyethylene glycol, polylactic acid, and polycaprolactone) with various molecular weights (PB-A and PB-B) was selected for the synthesis of nanoparticles (NPs) and thermosensitive gel (PB-C) by sequential ring-opening bulk copolymerization reaction. PB copolymers were characterized for their molecular weight and purity by 1H–NMR spectroscopy and crystallinity by PXRD. The macromolecule model drugs [lysozyme (Lyz ~ 14.5 kDa), IgG-Fab (~ 50 kDa), and IgG (~ 150 kDa)] were selected to delineate the effect of molecular weights on in vitro release profile of nanoformulations. Lyz-, Fab-, and IgG-encapsulated NPs were prepared by double emulsion solvent evaporation method. The entrapment efficiency (EE%) and drug loading (DL%) of macromolecules was higher for PB-B copolymers due to its higher molecular weight and hydrophobicity compare to PB-A. The particle size range of NPs was ~ 200–270 nm. In vitro release profiles of Lyz-, Fab-, and IgG-encapsulated in NPs alone and NPs suspended in gel (composite nanosystem) demonstrated a minimal burst release and drug release over a long period. The effect of hydrodynamic diameter of macromolecules and hydrophobicity of PB copolymers was investigated on the release profile of nanosystems. In vitro biocompatibility study showed negligible cytokine (IL-1, IL-6, and TNF-α) release, which confirmed the safety of the PB copolymers. Based on the results, it is anticipated that long-term ocular delivery of macromolecules can be achieved through composite nanosystems.

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Acknowledgements

Authors are thankful to Dr. Anil Kumar (Division of Pharmacology and Toxicology, UMKC) for providing the UV-Plate Reader facility, Dr. James Murochiwick (Department of Geosciences, UMKC) for helping in PXRD analyses, Dr. Kun Cheng (Division of Pharmaceutical Sciences,UMKC) for allowing us to use the freeze-dryer, and Dr. Bi-Botti C. Youan (Division of Pharmaceutical Sciences, UMKC) for allowing us to use the Zetasizer Nano ZS instrument.

Funding

This study was supported by the award number R01 EY09171-14 from the National Institutes of Health (NIH). The School of Graduate Studies (SGS), UMKC Research Grant and Graduate Assistant Fund (GAF), UMKC women’s Council provided the financial support.

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Author notes

  1. Nikhil Dhall, Zach Aulgur, and Siddhant Thukral contributed equally to this work.

Authors and Affiliations

  1. Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, 64108, USA

    Vibhuti Agrahari, Sulabh P. Patel, Xiaoyan Yang & Ashim K. Mitra

  2. Department of Biopharmaceutical Sciences, Bernard J. Dunn School of Pharmacy, Shenandoah University, 1775 N Sector Ct, Winchester, VA, 22601, USA

    Vibhuti Agrahari

  3. School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA

    Nikhil Dhall, Zach Aulgur & Siddhant Thukral

  4. Ira A. Fulton Schools of Engineering, Arizona State University, Tempe, AZ, 85281, USA

    Ryan Conley

Authors
  1. Vibhuti Agrahari
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  2. Sulabh P. Patel
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  3. Nikhil Dhall
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  4. Zach Aulgur
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  6. Xiaoyan Yang
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  7. Ryan Conley
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  8. Ashim K. Mitra
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Corresponding author

Correspondence to Ashim K. Mitra.

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Conflict of interest

The authors declare the conflict of interests with I-Novion Inc. and Genentech Inc.

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Agrahari, V., Patel, S.P., Dhall, N. et al. Nanoparticles in thermosensitive gel based composite nanosystem for ocular diseases. Drug Deliv. and Transl. Res. 8, 422–435 (2018). https://doi.org/10.1007/s13346-017-0435-y

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  • DOI: https://doi.org/10.1007/s13346-017-0435-y

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