Nanoincorporation of Plumbagin in Micelles Increase Its In Vivo Anti-Plasmodial Properties
Abstract
Background: The application of plumbagin (PLN), with a wide use in pharmaceutical science, is limited due to its low water solubility and poor bioavailability. Micelles can encapsulate hydrophobic drugs due to their hydrophobic core. The aim of this study was to develop and characterize a polymeric micelle formulation of PLN and evaluate its in vivo anti-plasmodial property.
Methods: The study was conducted at Zanjan University of Medical Sciences, Zanjan, Iran in 2018. The triblock copolymeric micelles of PLN was prepared by e-caprolactone ring-opening polymerization, by PEG as the macroinitiator and using Sn(Oct)2 for its catalytic properties . The synthesized nanoparticles were characterized by 1H NMR, FTIR, GPC, AFM, and DLS. The encapsulation efficiency, drug loading capacity, and drug release were measured by UV-Vis at 520 nm. Also in vivo anti-plasmodial potential of fabricated drug loaded micelle was investigated using the 4-day suppressive test against Plasmodium berghei infection in mice.
Results: The nanoparticles average diameter was obtained less than 80 nm. The loading capacity and encapsulation efficiencies were 18.9±1.3% and 81±0.78%, respectively. In vitro, PLN release studies showed a sustained-release pattern until 7 days in PLN-loaded micelles (M-PLN) and drug release rate in acidic condition was higher than neutral condition. In vivo, anti-plasmodial results against P. berghei displayed an 8-fold increase in anti-plasmodial activity of M-PLN when compared to free PLN at the tested dosage level on the 7th day.
Conclusion: Based on these results, PCL–PEG–PCL micelles have a great potential to be the carrier for PLN for the malaria targeting.
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24. Pradeepa V, Senthil-Nathan S, Sathish-Narayanan S, et al. Potential mode of action of a novel plumbagin as a mosquito repellent against the malarial vector Anopheles stephensi,(culicidae: Diptera). Pestic Biochem Physiol. 2016;134:84-93.
25. Sumsakul W, Plengsuriyakarn T, Chaijaroenkul W, Viyanant V, Karbwang J, Na-Bangchang K. Antimalarial activity of plumbagin in vitro and in animal models. BMC Complement Altern Med. 2014;14:15.
26. Aghajanzadeh M, Zamani M, Rashidzadeh H, Rostamizadeh K, Sharafi A, Danafar H. Amphiphilic y shaped miktoarm star copolymer for anticancer hydrophobic and hydrophilic drugs codelivery: Synthesis, characterization, in vitro, and in vivo biocompatibility study. J Biomed Mater Res A. 2018;106:2817-2826.
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28. Kooijmans S, Fliervoet L, Van Der Meel R, et al. Pegylated and targeted extracellular vesicles display enhanced cell specificity and circulation time. J Control Release. 2016;224:77-85.
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30. Manjili HK, Sharafi A, Danafar H, Hosseini M, Ramazani A, Ghasemi MH. Poly (caprolactone)–poly (ethylene glycol)–poly (caprolactone)(pcl–peg–pcl) nanoparticles: A valuable and efficient system for in vitro and in vivo delivery of curcumin. Rsc Advances. 2016;6:14403-14415.
31. Pisal S, Zainnuddin R, Nalawade P, Mahadik K, Kadam S. Drug release properties of polyethylene-glycol-treated ciprofloxacin-indion 234 complexes. AAPS Pharm Sci Tech. 2004;5:101-106.
32. Trivedi R, Kompella UB. Nanomicellar formulations for sustained drug delivery: Strategies and underlying principles. Nanomedicine. 2010;5:485-505.
33. Sunil Kumar M, Kiran Aithal B, Udupa N, et al. Formulation of plumbagin loaded long circulating pegylated liposomes: In vivo evaluation in c57bl/6j mice bearing b16f1 melanoma. Drug Delivery. 2011;18:511-522.
2. Ramazani A, Hamidnezhad R, Foroumadi A, Mirzaei SA, Maddahi S, Hassanzadeh SM. In vitro antiplasmodial activity and cytotoxic effect of (z)-2-benzylidene-4, 6-dimethoxybenzofuran-3 (2h)-one derivatives. Iran J Parasitol. 2016;11:371.
3. Ramazani A, Zakeri S, Sardari S, Khodakarim N, Djadidt ND. In vitro and in vivo anti-malarial activity of boerhavia elegans and solanum surattense. Malar J. 2010;9:124.
4. Heidari A, Keshavarz H. The drug resistance of Plasmodium falciparum and P. Vivax in Iran: A review article. Iran J Parasitol. 2021;16:173-185.
5. Mahmoudi S, Keshavarz H. Efficacy of phase 3 trial of rts, s/as01 malaria vaccine: The need for an alternative development plan. Human Vaccin Immunother. 2017;13:2098-2101.
6. Crane EA, Gademann K. Capturing biological activity in natural product fragments by chemical synthesis. Angewandte Chemie International Edition. 2016;55:3882-3902.
7. Jafarpour Azami S, Teimouri A, Keshavarz H et al. Curcumin nanoemulsion as a novel chemical for the treatment of acute and chronic toxoplasmosis in mice. Int J Nanomedicine. 2018; 13:7363-7374.
8. Muthaura C, Keriko J, Derese S, Yenesew A, Rukunga G. Investigation of some medicinal plants traditionally used for treatment of malaria in Kenya as potential sources of antimalarial drugs. Exp Parasitol. 2011;127:609-626.
9. Robert A, Benoit-Vical F, Dechy-Cabaret O, Meunier B. From classical antimalarial drugs to new compounds based on the mechanism of action of artemisinin. Pure Appl Chem. 2001;73:1173-1188.
10. Simonsen HT, Nordskjold JB, Smitt UW, Nyman U, Palpu P, Joshi P, Varughese G. In vitro screening of indian medicinal plants for antiplasmodial activity. J Ethnopharmacol. 2001;74:195-204.
11. Suraveratum N, Krungkrai SR, Leangaramgul P, Prapunwattana P, Krungkrai J. Purification and characterization of Plasmodium falciparum succinate dehydrogenase. Mol Biochem Parasitol. 2000;105:215-222.
12. Thiengsusuk A, Chaijaroenkul W, Na-Bangchang K. Antimalarial activities of medicinal plants and herbal formulations used in thai traditional medicine. Parasitol Res. 2013;112:1475-1481.
13. Hsieh YJ, Lin LC, Tsai TH. Measurement and pharmacokinetic study of plumbagin in a conscious freely moving rat using liquid chromatography/tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2006;844:1-5.
14. Sharma M, Sharma R, Jain DK, Saraf A. Enhancement of oral bioavailability of poorly water soluble carvedilol by chitosan nanoparticles: Optimization and pharmacokin-etic study. Int J Biol Macromol. 2019;135:246-260.
15. Rashidzadeh H, Rezaei SJT, Zamani S, Sarijloo E, Ramazani A. Ph-sensitive curcumin conjugated micelles for tumor triggered drug delivery. J Biomater Sci Polym Ed. 2021;32:320-336.
16. Rezaei SJT, Sarijloo E, Rashidzadeh H, Zamani S, Ramazani A, Hesami A, Mohammadi E. Ph-triggered prodrug micelles for cisplatin delivery: Preparation and in vitro/vivo evaluation. Reactive and Functional Polymers. 2020;146:104399.
17. Fattahi N, Ramazani A, Hamidi M, Parsa M, Rostamizadeh K, Rashidzadeh H. Enhancement of the brain delivery of methotrexate with administration of mid-chain ester prodrugs: In vitro and in vivo studies. Int J Pharm. 2021;600:120479.
18. Nosrati H, Salehiabar M, Bagheri Z, Rashidzadeh H, Davaran S, Danafar H. Preparation, characterization, and evaluation of amino acid modified magnetic nanoparticles: Drug delivery and mri contrast agent applications. Pharm Dev Technol. 2018;23:1156-1167.
19. Somasundaran P, Chin M, Latosiewicz UT, Tuller HL, Barbiellini B, Renugopalakrishnan V. Nanoscience and engineering for robust biosolar cells.In: Bionanotechnology II (pp.427-454). 2011. DOI:10.1201/b11374-23.
20. Kuskov AN, Kulikov PP, Goryachaya AV, Tzatzarakis MN, Tsatsakis AM, Velonia K, Shtilman MI. Self‐assembled amphiphilic poly‐n‐vinylpyrrolidone nanoparticles as carriers for hydrophobic drugs: Stability aspects. Journal of Applied Polymer Science. 2018;135:45637.
21. Asadi N, Annabi N, Mostafavi E, Anzabi M, Khalilov R, Saghfi S, Mehrizadeh M, Akbarzadeh A. Synthesis, characterization and in vitro evaluation of magnetic nanoparticles modified with pcl–peg–pcl for controlled delivery of 5fu. Artif Cells Nanomed Biotechnol. 2018;46:938-945.
22. Ramazani A, Keramati M, Malvandi H, Danafar H, Kheiri Manjili H. Preparation and in vivo evaluation of anti-plasmodial properties of artemisinin-loaded pcl–peg–pcl nanoparticles. Pharm Dev Technol. 2018;23:911-920.
23. Rashidzadeh H, Salimi M, Sadighian S, Rostamizadeh K, Ramazani A. In vivo antiplasmodial activity of curcumin-loaded nanostructured lipid carriers. Curr Drug Deliv. 2019;16:923-930.
24. Pradeepa V, Senthil-Nathan S, Sathish-Narayanan S, et al. Potential mode of action of a novel plumbagin as a mosquito repellent against the malarial vector Anopheles stephensi,(culicidae: Diptera). Pestic Biochem Physiol. 2016;134:84-93.
25. Sumsakul W, Plengsuriyakarn T, Chaijaroenkul W, Viyanant V, Karbwang J, Na-Bangchang K. Antimalarial activity of plumbagin in vitro and in animal models. BMC Complement Altern Med. 2014;14:15.
26. Aghajanzadeh M, Zamani M, Rashidzadeh H, Rostamizadeh K, Sharafi A, Danafar H. Amphiphilic y shaped miktoarm star copolymer for anticancer hydrophobic and hydrophilic drugs codelivery: Synthesis, characterization, in vitro, and in vivo biocompatibility study. J Biomed Mater Res A. 2018;106:2817-2826.
27. Najer A, Wu D, Nussbaumer MG, et al. An amphiphilic graft copolymer-based nanoparticle platform for reduction-responsive anticancer and antimalarial drug delivery. Nanoscale. 2016;8:14858-14869.
28. Kooijmans S, Fliervoet L, Van Der Meel R, et al. Pegylated and targeted extracellular vesicles display enhanced cell specificity and circulation time. J Control Release. 2016;224:77-85.
29. Sinlikhitkul N, Toochinda P, Lawtrakul L, Kuropakornpong P, Itharat A. Encapsulation of plumbagin using cyclodextrins to enhance plumbagin stability: Computational simulation, preparation, characterization, and application. J Incl Phenom Macrocycl Chem. 2019;93:229-243.
30. Manjili HK, Sharafi A, Danafar H, Hosseini M, Ramazani A, Ghasemi MH. Poly (caprolactone)–poly (ethylene glycol)–poly (caprolactone)(pcl–peg–pcl) nanoparticles: A valuable and efficient system for in vitro and in vivo delivery of curcumin. Rsc Advances. 2016;6:14403-14415.
31. Pisal S, Zainnuddin R, Nalawade P, Mahadik K, Kadam S. Drug release properties of polyethylene-glycol-treated ciprofloxacin-indion 234 complexes. AAPS Pharm Sci Tech. 2004;5:101-106.
32. Trivedi R, Kompella UB. Nanomicellar formulations for sustained drug delivery: Strategies and underlying principles. Nanomedicine. 2010;5:485-505.
33. Sunil Kumar M, Kiran Aithal B, Udupa N, et al. Formulation of plumbagin loaded long circulating pegylated liposomes: In vivo evaluation in c57bl/6j mice bearing b16f1 melanoma. Drug Delivery. 2011;18:511-522.
| Files | ||
| Issue | Vol 17 No 2 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v17i2.9538 | |
| Keywords | ||
| Plasmodium berghei Copolymers Micelles Plumbagin Sustained release | ||
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How to Cite
1.
Rashidzadeh H, Zamani P, Amiri M, Hassanzadeh SM, Ramazani A. Nanoincorporation of Plumbagin in Micelles Increase Its In Vivo Anti-Plasmodial Properties. Iran J Parasitol. 2022;17(2):202-213.
