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Stabilized oral nanostructured lipid carriers of Adefovir Dipivoxil as a potential liver targeting: Estimation of liver function panel and uptake following intravenous injection of radioiodinated indicator

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Abstract

Purpose

Adefovir dipivoxil (AD), a nucleoside reverse transcriptase inhibitor is effective against Hepatitis B virus. Its poor oral bioavailability leads to frequent administration causing severe adverse effects. Thereby the entrapment of AD within lipid nanoparticulate systems is a way of increasing AD oral bioavailability as a result of improving intestinal permeability with efficient liver-targeted delivery together with higher drug stability during storage.

Methods

AD-loaded nanostructured lipid carriers (AD-NLCs) were prepared via solvent emulsification diffusion technique adopting 24 full factorial design to study the effect of lipid percentage, presence of egg yolk lecithin, surfactant type and percentage on entrapment efficiency (E.E.%), particle size and percent in-vitro drug released after 8 h (Q8hrs).

Results

Formula (F12) showed E.E.% of 90.5 ± 0.2%, vesicle size of 240.2 ± 2.5 nm and Q8hrs of 58.55 ± 9.4% was selected as the optimum formula with desirability value of 0.757 based on highest EE%, lowest P.S. and Q8hrs. Further evaluation of the optimized formula using radioiodinated rose bengal (RIRB) in thioacetamide induced liver damage in Swiss Albino mice revealed a higher liver uptake of 22 ± 0.01% ID/g (percent injected dose/g organ) and liver uptake/Blood (T/B) ratio of 2.22 ± 0.067 post 2 h of I.V injection of RIRB compared to 9 ± 0.01% ID/g and 0.64 ± 0.017 in untreated group, respectively.

Conclusion

NLCs could be successfully used as oral drug delivery carriers of the antiviral drug Adefovir Dipivoxil to the liver with higher stability and oral bioavailability.

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Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Central Axis, 6th of October City, Giza, 12585, Egypt

    Shady M. Abd El-Halim

  2. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt

    Ghada A. Abdelbary & Maha M. Amin

  3. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy and Pharmaceutical Industry, Port Said University, Port said, 42526, Egypt

    Mohamed Y. Zakaria

  4. Department of Labeled Compounds, Hot Labs Center, Egyptian Atomic Energy Authority, Cairo, 13759, Egypt

    Hesham A. Shamsel-Din & Ahmed B. Ibrahim

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  1. Shady M. Abd El-Halim
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  2. Ghada A. Abdelbary
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Abd El-Halim, S.M., Abdelbary, G.A., Amin, M.M. et al. Stabilized oral nanostructured lipid carriers of Adefovir Dipivoxil as a potential liver targeting: Estimation of liver function panel and uptake following intravenous injection of radioiodinated indicator. DARU J Pharm Sci 28, 517–532 (2020). https://doi.org/10.1007/s40199-020-00355-8

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