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...
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MDPI AG
2023-02-01
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| author | Sayali Pravin Metkar Gasper Fernandes Ajinkya Nitin Nikam Soji Soman Sumit Birangal Raviraja N Seetharam Manjunath Bandu Joshi Srinivas Mutalik |
| author_facet | Sayali Pravin Metkar Gasper Fernandes Ajinkya Nitin Nikam Soji Soman Sumit Birangal Raviraja N Seetharam Manjunath Bandu Joshi Srinivas Mutalik |
| author_sort | Sayali Pravin Metkar |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T08:26:50Z |
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| id | doaj.art-fcae1ae0b7174ba2823bc2f91f6a619c |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-11T08:26:50Z |
| publishDate | 2023-02-01 |
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| series | Membranes |
| spelling | doaj.art-fcae1ae0b7174ba2823bc2f91f6a619c2023-11-16T22:02:36ZengMDPI AGMembranes2077-03752023-02-0113219310.3390/membranes13020193Mannosylated-Chitosan-Coated Andrographolide Nanoliposomes for the Treatment of Hepatitis: In Vitro and In Vivo EvaluationsSayali Pravin Metkar0Gasper Fernandes1Ajinkya Nitin Nikam2Soji Soman3Sumit Birangal4Raviraja N Seetharam5Manjunath Bandu Joshi6Srinivas Mutalik7Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaDepartment of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaDepartment of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaDepartment of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaDepartment of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaManipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaDepartment of Aging Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaDepartment of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaA 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.https://www.mdpi.com/2077-0375/13/2/193andrographolideliposomesmannosylated chitosanbioavailability enhancement |
| spellingShingle | Sayali Pravin Metkar Gasper Fernandes Ajinkya Nitin Nikam Soji Soman Sumit Birangal Raviraja N Seetharam Manjunath Bandu Joshi Srinivas Mutalik Mannosylated-Chitosan-Coated Andrographolide Nanoliposomes for the Treatment of Hepatitis: In Vitro and In Vivo Evaluations Membranes andrographolide liposomes mannosylated chitosan bioavailability enhancement |
| 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 | andrographolide liposomes mannosylated chitosan bioavailability enhancement |
| url | https://www.mdpi.com/2077-0375/13/2/193 |
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