1. 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.
- Author
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Abd El-Halim SM, Abdelbary GA, Amin MM, Zakaria MY, Shamsel-Din HA, and Ibrahim AB
- Subjects
- Adenine administration & dosage, Adenine pharmacokinetics, Administration, Oral, Animals, Chemical and Drug Induced Liver Injury physiopathology, Drug Stability, Injections, Intravenous, Iodine Radioisotopes chemistry, Lipids, Liver drug effects, Liver Function Tests, Mice, Nanoparticles, Organophosphonates administration & dosage, Particle Size, Rose Bengal chemistry, Adenine analogs & derivatives, Chemical and Drug Induced Liver Injury drug therapy, Liver physiopathology, Organophosphonates pharmacokinetics, Rose Bengal administration & dosage, Thioacetamide adverse effects
- 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 2
4 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. Graphical abstract.- Published
- 2020
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