Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

General Research Article

Characterization of Functionalized PLGA Nanoparticles Loaded with Mangiferin and Lupeol, and their Effect on BEAS-2B and HepG2 Cell Lines

Author(s): Razura-Carmona Francisco Fabián, Herrera-Martínez Mayra, Zamora-Gasga Víctor Manuel, Sáyago-Ayerdi Sonia Guadalupe, Pérez-Larios Alejandro* and Sánchez-Burgos Jorge Alberto*

Volume 23, Issue 10, 2023

Published on: 29 September, 2022

Page: [1174 - 1183] Pages: 10

DOI: 10.2174/1871520622666220617101515

Price: $65

Abstract

Lupeol (LP) and Mangiferin (MG) have beneficial effects on health. However, their pharmacokinetic properties can affect their bioavailability when administered orally. Therefore, their incorporation as a vehicle in a hybrid matrix of ZnO and PLGA could contribute to improving bioavailability.

Methods: This study aimed to develop this matrix and evaluate the optical and bioactive properties obtained by the solvent emulsion and evaporation methods. These were subjected to processes to evaluate their bioactivity in relation with topoisomerase.

Results: Functionalized treatment number 15 (TF15) showed the best results in studies of controlled release and encapsulation efficiency of lupeol (LP) and mangiferin (MG) (60.01 ± 1.24% and 57.71 ± 1.94%). The best treatment showed behavior as a topoisomerase II inhibitor (18.60 ± 1.55). The nanoparticles developed in this study did not show a cytotoxic effect on BEAS-2B, while HepG2, showed a decrease in viability (IC50 1549.96 ± 174.62 μg/mL). However, although the hemolytic activity is not shown after 1 h of exposure, morphological alterations caused by TF15 are observed at concentrations of 2500 and 1250 μg/mL.

Conclusion: The TF15 treatment shown maintaining antitopoisomerasa activity does and does not cytotoxixity for healthy cells and slows down the growth of cancer cells.

Keywords: Nanoparticles, functionalization, mangiferin, lupeol, biological activity, and cytotoxicity.

Graphical Abstract

[1]
Assadpour, E.; Mahdi Jafari, S. A systematic review on nanoencapsulation of food bioactive ingredients and nutraceuticals by various nanocarriers. Crit. Rev. Food Sci. Nutr., 2019, 59(19), 3129-3151.
[http://dx.doi.org/10.1080/10408398.2018.1484687] [PMID: 29883187]
[2]
Fattahi, A.; Ghiasi, M.; Mohammadi, P.; Hosseinzadeh, L.; Adibkia, K.; Mohammadi, G. Preparation and physicochemical characterization of prazosin conjugated PLGA nanoparticles for drug delivery of flutamide. Braz. J. Pharm. Sci., 2018, 54(4), 2-11.
[http://dx.doi.org/10.1590/s2175-97902018000417228]
[3]
Ali, A.; Ahmed, S. A review on chitosan and its nanocomposites in drug delivery. Int. J. Biol. Macromol., 2018, 109, 273-286.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.12.078] [PMID: 29248555]
[4]
Ehianeta, T.S.; Laval, S.; Yu, B. Bio- and chemical syntheses of mangiferin and congeners. Biofactors, 2016, 42(5), 445-458.
[http://dx.doi.org/10.1002/biof.1279] [PMID: 27774668]
[5]
Imran, M.; Arshad, M.S.; Butt, M.S.; Kwon, J.H.; Arshad, M.U.; Sultan, M.T. Mangiferin: A natural miracle bioactive compound against lifestyle related disorders. Lipids Health Dis., 2017, 16(1), 84.
[http://dx.doi.org/10.1186/s12944-017-0449-y] [PMID: 28464819]
[6]
Saha, S.; Sadhukhan, P.; Sil, P.C. Mangiferin: A xanthonoid with multipotent anti-inflammatory potential. Biofactors, 2016, 42(5), 459-474.
[http://dx.doi.org/10.1002/biof.1292] [PMID: 27219011]
[7]
Sekar, V.; Mani, S.; Malarvizhi, R.; Nithya, P.; Vasanthi, H.R. Antidiabetic effect of mangiferin in combination with oral hypoglycemic agents metformin and gliclazide. Phytomedicine, 2019, 59152901
[http://dx.doi.org/10.1016/j.phymed.2019.152901]
[8]
Khurana, R.K.; Kaur, R.; Lohan, S.; Singh, K.K.; Singh, B. Mangiferin: A promising anticancer bioactive. Pharm. Pat. Anal., 2016, 5(3), 169-181.
[http://dx.doi.org/10.4155/ppa-2016-0003] [PMID: 27088726]
[9]
Infante-Garcia, C.; Ramos-Rodriguez, J.J.; Delgado-Olmos, I.; Gamero-Carrasco, C.; Fernandez-Ponce, M.T.; Casas, L.; Mantell, C.; Garcia-Alloza, M. Long-term mangiferin extract treatment improves central pathology and cognitive deficits in APP/PS1 mice. Mol. Neurobiol., 2017, 54(6), 4696-4704.
[http://dx.doi.org/10.1007/s12035-016-0015-z] [PMID: 27443159]
[10]
Stohs, A.; Swaroop, S.J.; Moriyama, D.; Bagchi, H.; Ahmad, M.; Bagchi, T. A review on antioxidant, anti-inflammatory and gastroprotective abilities of mango (Magnifera indica) leaf extract and mangiferin. J. Nutrit. Health Food Sci., 2018, 5(3), 1-8.
[11]
Singh, B.; Sharma, R.A. Plant terpenes: Defense responses, phylogenetic analysis, regulation and clinical applications. 3 Biotech 2015, 5(2), 129-151.
[12]
Sánchez-Burgos, J.A. Isolation of lupeol from white oak leaves and its anti-inflammatory activity. Ind. Crops Prod., 2015, 77, 827-832.
[http://dx.doi.org/10.1016/j.indcrop.2015.09.056]
[13]
Rauth, S.; Ray, S.; Bhattacharyya, S.; Mehrotra, D.G.; Alam, N.; Mondal, G.; Nath, P.; Roy, A.; Biswas, J.; Murmu, N. Lupeol evokes anticancer effects in oral squamous cell carcinoma by inhibiting oncogenic EGFR pathway. Mol. Cell. Biochem., 2016, 417(1-2), 97-110.
[http://dx.doi.org/10.1007/s11010-016-2717-y] [PMID: 27206736]
[14]
Borgati, T.F. Synthesis by click reactions and antiplasmodial activity of lupeol 1,2,3-triazole derivatives. J. Braz. Chem. Soc., 2017, 28(10), 1850-1856.
[http://dx.doi.org/10.21577/0103-5053.20170013]
[15]
Nejabatdoust, A.; Salehzadeh, A.; Zamani, H.; Moradi-Shoeili, Z. Synthesis, characterization and functionalization of zno nanoparticles by glutamic acid (glu) and conjugation of zno@glu by thiosemicarbazide and its synergistic activity with ciprofloxacin against multi-drug resistant Staphylococcus aureus. J. Cluster Sci., 2019, 30(2), 329-336.
[http://dx.doi.org/10.1007/s10876-018-01487-3]
[16]
Delgado, J.L.; Hsieh, C.M.; Chan, N.L.; Hiasa, H. Topoisomerases as anticancer targets. Biochem. J., 2018, 475(2), 373-398.
[http://dx.doi.org/10.1042/BCJ20160583] [PMID: 29363591]
[17]
Cháirez-Ramírez, M.H.; Sánchez-Burgos, J.A.; Gomes, C.; Moreno-Jiménez, M.R.; González-Laredo, R.F.; Bernad-Bernad, M.J.; Medina-Torres, L.; Ramírez-Mares, M.V.; Gallegos-Infante, J.A.; Rocha-Guzmán, N.E. Morphological and release characterization of nanoparticles formulated with poly (dl-lactide-co-glycolide) (PLGA) and lupeol: In vitro permeability and modulator effect on NF-κB in Caco-2 cell system stimulated with TNF-κ. Food Chem. Toxicol., 2015, 85, 2-9.
[http://dx.doi.org/10.1016/j.fct.2015.08.003] [PMID: 26260749]
[18]
Gomes, C.; Moreira, R.G.; Castell-Perez, E. Poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped trans-cinnamaldehyde and eugenol for antimicrobial delivery applications. J. Food Sci., 2011, 76(2), N16-N24.
[http://dx.doi.org/10.1111/j.1750-3841.2010.01985.x] [PMID: 21535781]
[19]
Venugopal, V.; Kumar, K.J.; Muralidharan, S.; Parasuraman, S.; Raj, P.V.; Kumar, K.V. Optimization and in-vivo evaluation of isradipine nanoparticles using box-behnken design surface response methodology. OpenNano, 2016, 1, 1-15.
[http://dx.doi.org/10.1016/j.onano.2016.03.002]
[20]
Ritger, P.L.; Peppas, N.A. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J. Control. Release, 1987, 5(1), 37-42.
[http://dx.doi.org/10.1016/0168-3659(87)90035-6]
[21]
Siepmann, J.; Peppas, N.A. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv. Drug Deliv. Rev., 2012, 64, 163-174.
[http://dx.doi.org/10.1016/j.addr.2012.09.028]
[22]
Samadarsi, R.; Dutta, D. Design and characterization of mangiferin nanoparticles for oral delivery. J. Food Eng., 2019, 247, 80-94.
[http://dx.doi.org/10.1016/j.jfoodeng.2018.11.020]
[23]
Nitiss, J.L.; Nitiss, K.C. Yeast systems for demonstrating the targets of anti-topoisomerase II agents. Methods Mol. Biol., 2001, 95(1), 315-327.
[PMID: 11089243]
[24]
Kizhedath, A.; Wilkinson, S.; Glassey, J. Assessment of hepatotoxicity and dermal toxicity of butyl paraben and methyl paraben using HepG2 and HDFn in vitro models. Toxicol. In Vitro, 2019, 55, 108-115.
[http://dx.doi.org/10.1016/j.tiv.2018.12.007]
[25]
Zohra, M.; Fawzia, A. Hemolytic activity of different herbal extracts used in Algeria. Int. J. Pharm. Sci. Res., 2014, 5(08), 495-500.
[26]
Mora-Huertas, C.E.; Garrigues, O.; Fessi, H.; Elaissari, A. Nanocapsules prepared via nanoprecipitation and emulsification-diffusion methods: Comparative study. Eur. J. Pharm. Biopharm., 2012, 80(1), 235-239.
[http://dx.doi.org/10.1016/j.ejpb.2011.09.013] [PMID: 21983604]
[27]
Tirado, D.F.; Acevedo, D.; Herrera, A.P.; Herrera, A. Modeling the interaction energy of silica nanoparticles prepared in microemulsions. Ciencia e Ingenieria, 2015, 9(18), 95-101.
[28]
Mahapatro, A.; Singh, D.K. Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines. J. Nanobiotechnol., 2011, 9, 55.
[http://dx.doi.org/10.1186/1477-3155-9-55] [PMID: 22123084]
[29]
Yamanishi, Y.; Pauwels, E.; Saigo, H.; Stoven, V. Extracting sets of chemical substructures and protein domains governing drug-target interactions. J. Chem. Inf. Model., 2011, 51(5), 1183-1194.
[http://dx.doi.org/10.1021/ci100476q] [PMID: 21506615]
[30]
Veber, D.F.; Johnson, S.R.; Cheng, H.Y.; Smith, B.R.; Ward, K.W.; Kopple, K.D. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem., 2002, 45(12), 2615-2623.
[http://dx.doi.org/10.1021/jm020017n] [PMID: 12036371]
[31]
Spek, S.; Haeuser, M.; Schaefer, M.M.; Langer, K. Characterisation of PEGylated PLGA nanoparticles comparing the nanoparticle bulk to the particle surface using UV/vis spectroscopy, SEC, 1 H NMR spectroscopy, and X-ray photoelectron spectroscopy. Appl. Surf. Sci., 2015, 347, 378-385.
[http://dx.doi.org/10.1016/j.apsusc.2015.04.071]
[32]
Razura-Carmona, F.F. Mangiferin-loaded polymeric nanoparticles: Optical Cancers, 2019, 11, 1-17.
[33]
Chaitanya, K. Molecular structure, vibrational spectroscopic (FT-IR, FT-Raman), UV-vis spectra, first order hyperpolarizability, NBO analysis, HOMO and LUMO analysis, thermodynamic properties of benzophenone 2,4-dicarboxylic acid by ab initio HF and density functional method. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2012, 86, 159-173.
[http://dx.doi.org/10.1016/j.saa.2011.09.069] [PMID: 22137747]
[34]
Leet, J.E. Chemistry and structure elucidation of the kedarcidin chromophore. J. Am. Chem. Soc., 1993, 115, 8432-8443.
[http://dx.doi.org/10.1021/ja00071a062]
[35]
Kim, Y-G.; Oh, S-K.; Crooks, R.M. Preparation and characterization of 1−2 nm dendrimer-encapsulated gold nanoparticles having very narrow size distributions. Chem. Mater., 2004, 16(1), 167-172.
[http://dx.doi.org/10.1021/cm034932o]
[36]
Jain, D.; Athawale, R.; Bajaj, A.; Shrikhande, S.; Goel, P.N.; Gude, R.P. Studies on stabilization mechanism and stealth effect of poloxamer 188 onto PLGA nanoparticles. Colloids Surf. B Biointerfaces, 2013, 109, 59-67.
[http://dx.doi.org/10.1016/j.colsurfb.2013.03.027] [PMID: 23608470]
[37]
Shi, Y.; Xue, J.; Jia, L.; Du, Q.; Niu, J.; Zhang, D. Surface-modified PLGA nanoparticles with chitosan for oral delivery of tolbutamide. Colloids Surf. B Biointerfaces, 2018, 161, 67-72.
[http://dx.doi.org/10.1016/j.colsurfb.2017.10.037] [PMID: 29040836]
[38]
Alessandri, M.; Beretta, G.L.; Ferretti, E.; Mancia, A.; Khobta, A.; Capranico, G. Enhanced CPT Sensitivity of Yeast Cells and Selective relaxation of Ga14 motif-containing DNA by novel Gal4-topoisomerase I fusion proteins. J. Mol. Biol., 2004, 337(2), 295-305.
[39]
Sheng, C.; Miao, Z.; Zhang, W. Topoisomerase I inhibitors derived from natural products: Structure-activity relationships and antitumor potency. Stud. Nat. Prod. Chem., 2016, 47(2), 1-28.
[http://dx.doi.org/10.1016/B978-0-444-63603-4.00001-2]
[40]
Nitiss, J.; Wang, J.C. DNA topoisomerase-targeting antitumor drugs can be studied in yeast. Proc. Natl. Acad. Sci. USA, 1988, 85(20), 7501-7505.
[http://dx.doi.org/10.1073/pnas.85.20.7501] [PMID: 2845409]
[41]
Wal, P.; Wal, A.; Sharma, G.; Rai, A.K. Biological activities of lupeol. Sys. Rev. Pharm., 2011, 2(2), 96-103.
[http://dx.doi.org/10.4103/0975-8453.86298]
[42]
Gold-Smith, F.; Fernandez, A.; Bishop, K. Mangiferin and cancer: Mechanisms of action. Nutrients, 2016, 8(7), 16-20.
[http://dx.doi.org/10.3390/nu8070396] [PMID: 27367721]
[43]
Kumari, A.; Yadav, S.K.; Yadav, S.C. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf. B Biointerfaces, 2010, 75(1), 1-18.
[http://dx.doi.org/10.1016/j.colsurfb.2009.09.001] [PMID: 19782542]
[44]
He, Y.; Liu, F.; Zhang, L.; Wu, Y.; Hu, B.; Zhang, Y.; Li, Y.; Liu, H. Growth inhibition and apoptosis induced by lupeol, a dietary triterpene, in human hepatocellular carcinoma cells. Biol. Pharm. Bull., 2011, 34(4), 517-522.
[http://dx.doi.org/10.1248/bpb.34.517] [PMID: 21467639]
[45]
Nguyen, H.T.; Tran, T.H.; Kim, J.O.; Yong, C.S.; Nguyen, C.N. Enhancing the in vitro anti-cancer efficacy of artesunate by loading into poly-D, L-lactide-co-glycolide (PLGA) nanoparticles. Arch. Pharm. Res., 2015, 38(5), 716-724.
[http://dx.doi.org/10.1007/s12272-014-0424-3] [PMID: 24968925]
[46]
Muzykantov, V.R. Drug delivery by red blood cells: Vascular carriers designed by mother nature. Expert Opin. Drug Deliv., 2010, 7(4), 403-427.
[http://dx.doi.org/10.1517/17425241003610633] [PMID: 20192900]
[47]
Mota, A.H.; Direito, R.; Carrasco, M.P.; Rijo, P.; Ascensão, L.; Viana, A.S.; Rocha, J.; Eduardo-Figueira, M.; Rodrigues, M.J.; Custódio, L.; Kuplennik, N.; Sosnik, A.; Almeida, A.J.; Gaspar, M.M.; Reis, C.P. Combination of hyaluronic acid and PLGA particles as hybrid systems for viscosupplementation in osteoarthritis. Int. J. Pharm., 2019, 559, 13-22.
[http://dx.doi.org/10.1016/j.ijpharm.2019.01.017]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy