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A novel nanogel loaded with chitosan decorated bilosomes for transdermal delivery of terbutaline sulfate: artificial neural network optimization, in vitro characterization and in vivo evaluation

  • Shahira F. El Menshawe
  • Heba M. AboudEmail author
  • Mohammed H. Elkomy
  • Rasha M. Kharshoum
  • Amany M. Abdeltwab
Original Article

Abstract

The objective of the present work was to formulate, optimize, and evaluate transdermal terbutaline sulfate (TBN)-loaded bilosomes (BLS) in gel, compared to conventional oral TBN solution and transdermal gel loaded with free TBN, aiming at evading the hepatic first-pass metabolism. A face-centered central composite design was adopted to observe the effects of different formulation variables on TBN-BLS, and artificial neural network (ANN) modeling was employed to optimize TBN-BLS. TBN-BLS were prepared by a thin film hydration method integrating soybean phosphatidylcholine and cholesterol as a lipid phase and sodium deoxycholate (SDC) as a surfactant with or without the coating of chitosan (CTS). After being subjected to physicochemical characterization, TBN-BLS were enrolled in a histopathological study and pharmacokinetic investigation in a rat model. The optimized TBN chitosan-coated bilosomes (TBN-CTS-BLS) were spherical vesicles (245.13 ± 10.23 nm) with adequate entrapment efficiency (65.25 ± 5.51%) and good permeation characteristics (340.11 ± 22.34 μg/cm2). The TBN-CTS-BLS gel formulation was well-tolerated with no inflammatory signs manifested upon histopathological evaluation. The pharmacokinetic study revealed that the optimized TBN-CTS-BLS formulation successively enhanced the bioavailability of TBN by about 2.33-fold and increased t1/2 to about 6.21 ± 0.24 h as compared to the oral solution. These findings support the prospect use of BLS as active and safe transdermal carrier for TBN in the treatment of asthma.

Graphical Abstract

Keywords

Terbutaline sulfate Bilosomes Transdermal Artificial neural network Pharmacokinetic studies 

Notes

Compliance with ethical standards

The animal ethical committee of Beni-Suef University approved this protocol.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

13346_2019_688_MOESM1_ESM.docx (257 kb)
ESM 1 (DOCX 256 kb)

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Copyright information

© Controlled Release Society 2019

Authors and Affiliations

  • Shahira F. El Menshawe
    • 1
  • Heba M. Aboud
    • 1
    Email author
  • Mohammed H. Elkomy
    • 1
    • 2
  • Rasha M. Kharshoum
    • 1
  • Amany M. Abdeltwab
    • 1
  1. 1.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyBeni-Suef UniversityBeni-SuefEgypt
  2. 2.Department of Pharmaceutics, College of PharmacyJouf UniversitySakakaSaudi Arabia

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