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Development of Interleukin-2 Loaded Chitosan-Based Nanogels Using Artificial Neural Networks and Investigating the Effects on Wound Healing in Rats

AAPS PharmSciTech volume 18, pages 1019–1030 (2017)Cite this article

ABSTRACT

The aim of this study was to develop and characterize rh- IL-2 loaded chitosan-based nanogels for the healing of wound incision in rats. Nanogels were prepared using chitosan and bovine serum albumin (BSA) by ionic gelation method and high temperature application, respectively. Particle size, zeta potential, and polydispersity index were measured for characterization of nanogels. The morphology of nanogels was examined by using SEM and AFM. The IL-2 loading capacity of nanogels was determined using ELISA method. In vitro release of IL-2 from nanogels was performed using Franz diffusion cells. Artificial neural network (ANN) models were developed using selected input parameters (stirring rate, chitosan%, BSA%, TPP%) where particle size was an output parameter for IL-2 free nanogels. Wound healing effect of IL-2 loaded chitosan-TPP nanogel was evaluated by determining the malondialdehyde (MDA) and glutathione (GSH) levels of wound tissues in rats. The particle size of IL-2 loaded chitosan-TPP nanogels was found to be larger than that of IL-2 loaded BSA-based chitosan nanogels. Drug loading capacity of nanogels was found 100% ± 0.010 for both nanogels. IL-2 was released slowly after the initial burst effect. According to SEM and AFM imaging, BSA-chitosan nanogel particles were of nanometer size and presented a swelling tendency, and chitosan-TPP nanogel particles were found to be spherical and homogenously dispersed. IL-2 loaded chitosan-TPP nanogel was found suitable for improving wound healing because it decreased the MDA levels and increased the GSH levels wound tissues comparing to control group.

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Acknowledgements

This study was supported by Gazi University Scientific Research Foundation (Project Number: 02/2009-11).

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Author notes

  1. Canan Aslan

    Present address: Sanovel Pharmaceuticals, İstanbul, Turkey

Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, Gazi University, Etiler, 06330, Ankara, Turkey

    Canan Aslan, Nevin Çelebi & İ. Tuncer Değim

  2. Department of Immunology, Faculty of Medicine, Gazi University, Beşevler, 06510, Ankara, Turkey

    Ayşegül Atak

  3. Department of Physiology, Faculty of Medicine, Gazi University, Beşevler, 06510, Ankara, Turkey

    Çiğdem Özer

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  1. Canan Aslan
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  2. Nevin Çelebi
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Correspondence to Nevin Çelebi.

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Guest Editors: Claudio Salomon, Francisco Goycoolea, and Bruno Moerschbacher

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Aslan, C., Çelebi, N., Değim, İ.T. et al. Development of Interleukin-2 Loaded Chitosan-Based Nanogels Using Artificial Neural Networks and Investigating the Effects on Wound Healing in Rats. AAPS PharmSciTech 18, 1019–1030 (2017). https://doi.org/10.1208/s12249-016-0662-4

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  • DOI: https://doi.org/10.1208/s12249-016-0662-4

KEY WORDS

  • artificial neural network
  • chitosan
  • interleukin-2
  • nanogel
  • wound healing