Manal A Elsheikh1,2, Yosra S R Elnaggar3,4, Dina Y Otify5, Ossama Y Abdallah1. 1. Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 1-Azarita Square, Alexandria, Egypt. 2. Department of Pharmaceutics, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt. 3. Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 1-Azarita Square, Alexandria, Egypt. yosra_pharm@yahoo.com. 4. Department of Pharmaceutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt. yosra_pharm@yahoo.com. 5. Center of Excellent for Research in Regenerative Medicine and its Application (CERRMA), Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Abstract
PURPOSE: To develop novel bioactive-chylomicrons to solve oral delivery obstacles of Berberine chloride and target the lymphatic system. METHODS: Berberine-loaded bioactive-chylomicrons were prepared and underwent full in vitro characterization. Intestinal permeability was appraised via both non-everted gut sac model and Caco-2 cell model. Furthermore, Bioactive-chylomicrons' cellular uptake and distribution were examined by laser scanning confocal microscopy. Finally, a novel chylomicron flow-blockage assay on tissue and cellular levels were elaborated to assess the lymphatic targeting ability. RESULTS: Berberine-loaded chylomicrons showed spherical vesicles of size (175.6 nm), PDI (0.229), zeta potential (-16 .6 mV) and entrapment efficiency (95.5%). Ex-vivo intestinal permeability studies demonstrated 10.5 fold enhancement in permeability of Berberine-loaded chylomicrons over free Berberine. Moreover, Caco-2 studies revealed significant improvement in chylomicrons' permeability and cellular uptake. Furthermore, confocal microscopy analyses revealed 2 fold increase in berberine-loaded chylomicrons' intracellular fluorescence. Lymphatic targeting models were successfully elaborated using cycloheximide protein synthesis inhibitor. Such models demonstrated 47 and 27.5% reduction in ex-vivo and Caco-2 permeability respectively. Finally, a good rank order correlation was established between different permeability assessment techniques. CONCLUSION: The findings shed the light on the underlying mechanisms of Berberine bioavailability improvement. Consequently, berberine-loaded chylomicrons could be considered as promising bioactive-nanocarriers for Berberine lymphatic targeting and bioavailability improvement.
PURPOSE: To develop novel bioactive-chylomicrons to solve oral delivery obstacles of Berberine chloride and target the lymphatic system. METHODS:Berberine-loaded bioactive-chylomicrons were prepared and underwent full in vitro characterization. Intestinal permeability was appraised via both non-everted gut sac model and Caco-2 cell model. Furthermore, Bioactive-chylomicrons' cellular uptake and distribution were examined by laser scanning confocal microscopy. Finally, a novel chylomicron flow-blockage assay on tissue and cellular levels were elaborated to assess the lymphatic targeting ability. RESULTS:Berberine-loaded chylomicrons showed spherical vesicles of size (175.6 nm), PDI (0.229), zeta potential (-16 .6 mV) and entrapment efficiency (95.5%). Ex-vivo intestinal permeability studies demonstrated 10.5 fold enhancement in permeability of Berberine-loaded chylomicrons over free Berberine. Moreover, Caco-2 studies revealed significant improvement in chylomicrons' permeability and cellular uptake. Furthermore, confocal microscopy analyses revealed 2 fold increase in berberine-loaded chylomicrons' intracellular fluorescence. Lymphatic targeting models were successfully elaborated using cycloheximide protein synthesis inhibitor. Such models demonstrated 47 and 27.5% reduction in ex-vivo and Caco-2 permeability respectively. Finally, a good rank order correlation was established between different permeability assessment techniques. CONCLUSION: The findings shed the light on the underlying mechanisms of Berberine bioavailability improvement. Consequently, berberine-loaded chylomicrons could be considered as promising bioactive-nanocarriers for Berberine lymphatic targeting and bioavailability improvement.
Authors: Hannu Mönkkönen; Soili Törmälehto; Kari Asunmaa; Riku Niemi; Seppo Auriola; Jouko Vepsäläinen; Jukka Mönkkönen Journal: Eur J Pharm Sci Date: 2003-05 Impact factor: 4.384
Authors: Haidy Abbas; Nesrine S El Sayed; Nancy Abdel Hamid Abou Youssef; Passent M E Gaafar; Mohamed R Mousa; Ahmed M Fayez; Manal A Elsheikh Journal: Pharmaceutics Date: 2022-05-06 Impact factor: 6.525