Mannosylated-Chitosan-Coated Andrographolide Nanoliposomes for the Treatment of Hepatitis: In Vitro and In Vivo Evaluations

Overview

Journal Membranes (Basel)

Date 2023 Feb 25

PMID 36837696

Authors

Sayali Pravin Metkar

Gasper Fernandes

Ajinkya Nitin Nikam

Soji Soman

Sumit Birangal

Raviraja N Seetharam

Manjunath Bandu Joshi

Srinivas Mutalik

Affiliations

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Abstract

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.

Citing Articles

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References

Esfandiari F, Motazedian M, Asgari Q, Morowvat M, Molaei M, Heli H . Paromomycin-loaded mannosylated chitosan nanoparticles: Synthesis, characterization and targeted drug delivery against leishmaniasis. Acta Trop. 2019; 197:105072. DOI: 10.1016/j.actatropica.2019.105072. View

Jain P, Khurana N, Pounikar Y, Gajbhiye A, Kharya M . Enhancement of absorption and hepatoprotective potential through soya-phosphatidylcholine-andrographolide vesicular system. J Liposome Res. 2013; 23(2):110-8. DOI: 10.3109/08982104.2012.753456. View

Das S, Pradhan G, Das S, Nath D, Das Saha K . Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage. Chem Biol Interact. 2015; 242:281-9. DOI: 10.1016/j.cbi.2015.10.011. View

Cao Y, Dong X, Chen X . Polymer-Modified Liposomes for Drug Delivery: From Fundamentals to Applications. Pharmaceutics. 2022; 14(4). PMC: 9026371. DOI: 10.3390/pharmaceutics14040778. View

Jiang Y, Wang F, Xu H, Liu H, Meng Q, Liu W . Development of andrographolide loaded PLGA microspheres: optimization, characterization and in vitro-in vivo correlation. Int J Pharm. 2014; 475(1-2):475-84. DOI: 10.1016/j.ijpharm.2014.09.016. View

Friesner R, Banks J, Murphy R, Halgren T, Klicic J, Mainz D . Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem. 2004; 47(7):1739-49. DOI: 10.1021/jm0306430. View

Li J, Abel R, Zhu K, Cao Y, Zhao S, Friesner R . The VSGB 2.0 model: a next generation energy model for high resolution protein structure modeling. Proteins. 2011; 79(10):2794-812. PMC: 3206729. DOI: 10.1002/prot.23106. View

Roy P, Das S, Auddy R, Mukherjee A . Engineered andrographolide nanosystems for smart recovery in hepatotoxic conditions. Int J Nanomedicine. 2014; 9:4723-35. PMC: 4200072. DOI: 10.2147/IJN.S65262. View

Nguyen T, Huang L, Liu L, Abdalla A, Gauthier M, Yang G . Chitosan-coated nano-liposomes for the oral delivery of berberine hydrochloride. J Mater Chem B. 2020; 2(41):7149-7159. DOI: 10.1039/c4tb00876f. View

10.

Agrawal M, Saraf S, Pradhan M, Patel R, Singhvi G, Ajazuddin . Design and optimization of curcumin loaded nano lipid carrier system using Box-Behnken design. Biomed Pharmacother. 2021; 141:111919. DOI: 10.1016/j.biopha.2021.111919. View

11.

AlSawaftah N, Awad N, Paul V, Kawak P, Al-Sayah M, Husseini G . Transferrin-modified liposomes triggered with ultrasound to treat HeLa cells. Sci Rep. 2021; 11(1):11589. PMC: 8172941. DOI: 10.1038/s41598-021-90349-6. View

12.

Chi C, Zhang C, Liu Y, Nie H, Zhou J, Ding Y . Phytosome-nanosuspensions for silybin-phospholipid complex with increased bioavailability and hepatoprotection efficacy. Eur J Pharm Sci. 2020; 144:105212. DOI: 10.1016/j.ejps.2020.105212. View

13.

Arif M, Ahmad R, Sharaf M, Samreen , Muhammad J, Abdalla M . Antibacterial and antibiofilm activity of mannose-modified chitosan/PMLA nanoparticles against multidrug-resistant Helicobacter pylori. Int J Biol Macromol. 2022; 223(Pt A):418-432. DOI: 10.1016/j.ijbiomac.2022.10.265. View

14.

Elsayad M, Mowafy H, Zaky A, Samy A . Chitosan caged liposomes for improving oral bioavailability of rivaroxaban: and evaluation. Pharm Dev Technol. 2020; 26(3):316-327. DOI: 10.1080/10837450.2020.1870237. View

15.

Maiti K, Mukherjee K, Murugan V, Saha B, Mukherjee P . Enhancing bioavailability and hepatoprotective activity of andrographolide from Andrographis paniculata, a well-known medicinal food, through its herbosome. J Sci Food Agric. 2010; 90(1):43-51. DOI: 10.1002/jsfa.3777. View

16.

Narayan R, Singh M, Ranjan O, Nayak Y, Garg S, Shavi G . Development of risperidone liposomes for brain targeting through intranasal route. Life Sci. 2016; 163:38-45. DOI: 10.1016/j.lfs.2016.08.033. View

17.

Sinha J, Mukhopadhyay S, Das N, Basu M . Targeting of liposomal andrographolide to L. donovani-infected macrophages in vivo. Drug Deliv. 2001; 7(4):209-13. DOI: 10.1080/107175400455137. View

18.

Fernandes G, Pusuluri S, Nikam A, Birangal S, Shenoy G, Mutalik S . Solvent Free Twin Screw Processed Silybin Nanophytophospholipid: In Silico, In Vitro and In Vivo Insights. Pharmaceutics. 2022; 14(12). PMC: 9782009. DOI: 10.3390/pharmaceutics14122729. View

19.

Tu Y, Sun D, Zhang J, Jiang Z, Chen Y, Zeng X . Preparation and characterisation of andrographolide niosomes and its anti-hepatocellular carcinoma activity. J Microencapsul. 2013; 31(4):307-16. DOI: 10.3109/02652048.2013.843727. View

20.

Bothiraja C, Pawar A, Dama G, Joshi P, Shaikh K . Novel solvent-free gelucire extract of Plumbago zeylanica using non-everted rat intestinal sac method for improved therapeutic efficacy of plumbagin. J Pharmacol Toxicol Methods. 2012; 66(1):35-42. DOI: 10.1016/j.vascn.2012.05.007. View