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Mannosylated-Chitosan-Coated Andrographolide Nanoliposomes for the Treatment of Hepatitis: In Vitro and In Vivo Evaluations
A key diterpene lactone of Andrographis paniculata, i.e., andrographolide (AG), exhibits a variety of physiological properties, including hepatoprotection. The limited solubility, short half-life, and poor bioavailability limits the pharmacotherapeutic potential of AG. Therefore, in this study we ai...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965523/ https://www.ncbi.nlm.nih.gov/pubmed/36837696 http://dx.doi.org/10.3390/membranes13020193 |
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author | Metkar, Sayali Pravin Fernandes, Gasper Nikam, Ajinkya Nitin Soman, Soji Birangal, Sumit Seetharam, Raviraja N Joshi, Manjunath Bandu Mutalik, Srinivas |
author_facet | Metkar, Sayali Pravin Fernandes, Gasper Nikam, Ajinkya Nitin Soman, Soji Birangal, Sumit Seetharam, Raviraja N Joshi, Manjunath Bandu Mutalik, Srinivas |
author_sort | Metkar, Sayali Pravin |
collection | PubMed |
description | A key diterpene lactone of Andrographis paniculata, i.e., andrographolide (AG), exhibits a variety of physiological properties, including hepatoprotection. The limited solubility, short half-life, and poor bioavailability limits the pharmacotherapeutic potential of AG. Therefore, in this study we aimed to formulate and optimize AG-loaded nanoliposomes (AGL) using the Design of Experiment (DOE) approach and further modify the surface of the liposomes with mannosylated chitosan to enhance its oral bioavailability. Physical, morphological, and solid-state characterization was performed to confirm the formation of AGL and Mannosylated chitosan-coated AGL (MCS-AGL). Molecular docking studies were conducted to understand the ligand (MCS) protein (1EGG) type of interaction. Further, in vitro release, ex vivo drug permeation, and in vivo pharmacokinetics studies were conducted. The morphological studies confirmed that AGL was spherical and a layer of MCS coating was observed on their surface, forming the MCS-AGL. Further increase in the particle size and change in the zeta potential of MCS-AGL confirms the coating on the surface of AGL (375.3 nm, 29.80 mV). The in vitro drug release data reflected a sustained drug release profile from MCS-AGL in the phosphate buffer (pH 7.4) with 89.9 ± 2.13% drug release in 8 h. Ex vivo permeation studies showed higher permeation of AG from MCS-AGL (1.78-fold) compared to plain AG and AGL (1.37-fold), indicating improved permeability profiles of MCS-AGL. In vivo pharmacokinetic studies inferred that MCS-AGL had a 1.56-fold enhancement in AUC values compared to plain AG, confirming that MCS-AGL improved the bioavailability of AG. Additionally, the 2.25-fold enhancement in the MRT proves that MCS coating also enhances the in vivo stability and retention of AG (stealth effect). MCS as a polymer therefore has a considerable potential for improving the intestinal permeability and bioavailability of poorly soluble and permeable drugs or phytoconstituents when coated over nanocarriers. |
format | Online Article Text |
id | pubmed-9965523 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99655232023-02-26 Mannosylated-Chitosan-Coated Andrographolide Nanoliposomes for the Treatment of Hepatitis: In Vitro and In Vivo Evaluations Metkar, Sayali Pravin Fernandes, Gasper Nikam, Ajinkya Nitin Soman, Soji Birangal, Sumit Seetharam, Raviraja N Joshi, Manjunath Bandu Mutalik, Srinivas Membranes (Basel) Article A key diterpene lactone of Andrographis paniculata, i.e., andrographolide (AG), exhibits a variety of physiological properties, including hepatoprotection. The limited solubility, short half-life, and poor bioavailability limits the pharmacotherapeutic potential of AG. Therefore, in this study we aimed to formulate and optimize AG-loaded nanoliposomes (AGL) using the Design of Experiment (DOE) approach and further modify the surface of the liposomes with mannosylated chitosan to enhance its oral bioavailability. Physical, morphological, and solid-state characterization was performed to confirm the formation of AGL and Mannosylated chitosan-coated AGL (MCS-AGL). Molecular docking studies were conducted to understand the ligand (MCS) protein (1EGG) type of interaction. Further, in vitro release, ex vivo drug permeation, and in vivo pharmacokinetics studies were conducted. The morphological studies confirmed that AGL was spherical and a layer of MCS coating was observed on their surface, forming the MCS-AGL. Further increase in the particle size and change in the zeta potential of MCS-AGL confirms the coating on the surface of AGL (375.3 nm, 29.80 mV). The in vitro drug release data reflected a sustained drug release profile from MCS-AGL in the phosphate buffer (pH 7.4) with 89.9 ± 2.13% drug release in 8 h. Ex vivo permeation studies showed higher permeation of AG from MCS-AGL (1.78-fold) compared to plain AG and AGL (1.37-fold), indicating improved permeability profiles of MCS-AGL. In vivo pharmacokinetic studies inferred that MCS-AGL had a 1.56-fold enhancement in AUC values compared to plain AG, confirming that MCS-AGL improved the bioavailability of AG. Additionally, the 2.25-fold enhancement in the MRT proves that MCS coating also enhances the in vivo stability and retention of AG (stealth effect). MCS as a polymer therefore has a considerable potential for improving the intestinal permeability and bioavailability of poorly soluble and permeable drugs or phytoconstituents when coated over nanocarriers. MDPI 2023-02-03 /pmc/articles/PMC9965523/ /pubmed/36837696 http://dx.doi.org/10.3390/membranes13020193 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Metkar, Sayali Pravin Fernandes, Gasper Nikam, Ajinkya Nitin Soman, Soji Birangal, Sumit Seetharam, Raviraja N Joshi, Manjunath Bandu Mutalik, Srinivas Mannosylated-Chitosan-Coated Andrographolide Nanoliposomes for the Treatment of Hepatitis: In Vitro and In Vivo Evaluations |
title | Mannosylated-Chitosan-Coated Andrographolide Nanoliposomes for the Treatment of Hepatitis: In Vitro and In Vivo Evaluations |
title_full | Mannosylated-Chitosan-Coated Andrographolide Nanoliposomes for the Treatment of Hepatitis: In Vitro and In Vivo Evaluations |
title_fullStr | Mannosylated-Chitosan-Coated Andrographolide Nanoliposomes for the Treatment of Hepatitis: In Vitro and In Vivo Evaluations |
title_full_unstemmed | Mannosylated-Chitosan-Coated Andrographolide Nanoliposomes for the Treatment of Hepatitis: In Vitro and In Vivo Evaluations |
title_short | Mannosylated-Chitosan-Coated Andrographolide Nanoliposomes for the Treatment of Hepatitis: In Vitro and In Vivo Evaluations |
title_sort | mannosylated-chitosan-coated andrographolide nanoliposomes for the treatment of hepatitis: in vitro and in vivo evaluations |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965523/ https://www.ncbi.nlm.nih.gov/pubmed/36837696 http://dx.doi.org/10.3390/membranes13020193 |
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