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Swellable Ciprofloxacin-Loaded Nano-in-Micro Hydrogel Particles for Local Lung Drug Delivery

  • Research Article
  • Theme: Advances in Formulation and Device Technologies for Pulmonary Drug Delivery
  • Published:
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ABSTRACT

Incorporation of drug-loaded nanoparticles into swellable and respirable microparticles is a promising strategy to avoid rapid clearance from the lung and achieve sustained drug release. In this investigation, a copolymer of polyethylene glycol grafted onto phthaloyl chitosan (PEG-g-PHCs) was synthesized and then self-assembled with ciprofloxacin to form drug-loaded nanoparticles. The nanoparticles and free drug were encapsulated into respirable and swellable alginate micro hydrogel particles and assessed as a novel system for sustained pulmonary drug delivery. Particle size, morphology, dynamic swelling profile, and in vitro drug release were investigated. Results showed that drug-loaded nanoparticles with size of 218 nm were entrapped into 3.9-μm micro hydrogel particles. The dry nano-in-micro hydrogel particles exhibited a rapid initial swelling within 2 min and showed sustained drug release. Preliminary in vivo pharmacokinetic studies were performed with formulations delivered to rats by intratracheal insufflation. Ciprofloxacin concentrations in plasma and in lung tissue and lavage were measured up to 7 h. The swellable particles showed lower ciprofloxacin levels in plasma than the controlled group (a mixture of lactose with micronized ciprofloxacin), while swellable particles achieved higher concentrations in lung tissue and lavage, indicating the swellable particles could be used for controlling drug release and prolonging lung drug concentrations.

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ACKNOWLEDGMENTS

Research reported in this publication was supported by the National Heart, Lung, and Blood Institute, National Institute of Environmental Health Sciences, and National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under award numbers of R21HL092812 and R03EB006892. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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The authors report no declarations of interest.

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Authors and Affiliations

  1. Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 West University Avenue, PHR 4.214, Austin, Texas, 78712, USA

    Ju Du & Hugh D. Smyth

  2. Chemistry Department, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt

    Ibrahim M. El-Sherbiny

  3. Center for Materials Science, Zewail City of Science and Technology, Sheikh Zayed District, 6th October City, Giza, 12588, Egypt

    Ibrahim M. El-Sherbiny

Authors
  1. Ju Du
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  2. Ibrahim M. El-Sherbiny
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  3. Hugh D. Smyth
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Correspondence to Ibrahim M. El-Sherbiny or Hugh D. Smyth.

Additional information

Guest Editors: Paul B. Myrdal and Steve W. Sein

Ju Du and Ibrahim M. El-Sherbiny had contributed equally to this work.

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Du, J., El-Sherbiny, I.M. & Smyth, H.D. Swellable Ciprofloxacin-Loaded Nano-in-Micro Hydrogel Particles for Local Lung Drug Delivery. AAPS PharmSciTech 15, 1535–1544 (2014). https://doi.org/10.1208/s12249-014-0176-x

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  • DOI: https://doi.org/10.1208/s12249-014-0176-x

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