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Nanoemulsomes for Enhanced Oral Bioavailability of the Anticancer Phytochemical Andrographolide: Characterization and Pharmacokinetics

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Abstract

Andrographolide (AG) is an antitumor phytochemical that acts against non-Hodgkin’s lymphoma. However, AG shows low oral bioavailability due to extensive first-pass metabolism and P-glycoprotein efflux. Novel biocompatible lipoprotein-simulating nanosystems, emulsomes (EMLs), have gained significant attention due to their composition of natural components, in addition to being lymphotropic. Loading AG on EMLs is believed to mitigate the disadvantage of AG and enhance its lymphatic transport. This study developed a chylomicron-simulating system (EMLs) as a novel tool to overcome the AG oral delivery obstacles. Optimized EML-AG had a promising vesicular size of 281.62 ± 1.73 nm, a zeta potential of − 22.73 ± 0.06 mV, and a high entrapment efficiency of 96.55% ± 0.25%, which favors lymphatic targeting. In vivo pharmacokinetic studies of EML-AG showed significant enhancement (> sixfold increase) in the rate and extent of AG absorption compared with free AG. However, intraperitoneal injection of a cycloheximide inhibitor caused a significant decrease in AG absorption (~ 52%), confirming the lymphatic targeting potential of EMLs. Therefore, EMLs can be a promising novel nanoplatform for circumventing AG oral delivery obstacles and provide targeted delivery to the lymphatic system at a lower dose with fewer side effects.

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Abbreviations

AG:

Andrographolide

EML:

Emulsome

EML-AG:

Andrographolide-loaded emulsome

PC:

Phosphatidylcholine

Chol:

Cholesterol

CA:

Compritol 888 ATO

CHX:

Cycloheximide

PDI:

Polydispersity index

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Author notes

  1. Manal A. Elsheikh and Samar A. Rizk contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt

    Manal A. Elsheikh

  2. Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 1 Khartoum Square, Azarita, Messalla Post Office, P.O. Box 21521, Alexandria, Egypt

    Samar A. Rizk, Yosra S. R. Elnaggar & Ossama Y. Abdallah

  3. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt

    Samar A. Rizk & Yosra S. R. Elnaggar

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  1. Manal A. Elsheikh
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Contributions

Samar A. Rizk: Methodology, practical work, investigation, resources, writing (original draft), visualization, data curation, formal analysis.

Manal A. Elsheikh: Theoretical framework, data statistical analyses, results interpretation, writing—review and editing.

Yosra S.R. Elnaggar: Conceptualization, writing (review and editing), supervision, validation, international publishing process.

Ossama Y. Abdallah: Conceptualization, resources, validation and supervision.

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Correspondence to Yosra S. R. Elnaggar.

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Elsheikh, M.A., Rizk, S.A., Elnaggar, Y.S.R. et al. Nanoemulsomes for Enhanced Oral Bioavailability of the Anticancer Phytochemical Andrographolide: Characterization and Pharmacokinetics. AAPS PharmSciTech 22, 246 (2021). https://doi.org/10.1208/s12249-021-02112-9

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