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


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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.

About the authors

Razura-Carmona Fabián

Tecnológico Nacional de México / I.T.Tepic, Laboratorio Integral de Investigación en Alimentos,, Avenida Instituto Tecnológico No. 2595,

Email: info@benthamscience.net

Herrera-Martínez Mayra

Instituto de Farmacobiología,, Universidad de la Cañada,

Email: info@benthamscience.net

Zamora-Gasga Manuel

Tecnológico Nacional de México / I.T.Tepic, Laboratorio Integral de Investigación en Alimentos, Avenida Instituto Tecnológico No. 2595

Email: info@benthamscience.net

Sáyago-Ayerdi Guadalupe

Tecnológico Nacional de México / I.T.Tepic, Laboratorio Integral de Investigación en Alimentos, Avenida Instituto Tecnológico No. 2595,

Email: info@benthamscience.net

Pérez-Larios Alejandro

, Universidad de Guadalajara, Centro Universitario Los Altos

Author for correspondence.
Email: info@benthamscience.net

Sánchez-Burgos Alberto

Tecnológico Nacional de México / I.T.Tepic, Laboratorio Integral de Investigación en Alimentos, Avenida Instituto Tecnológico No. 2595,

Author for correspondence.
Email: info@benthamscience.net

References

  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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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 doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1016/j.ijpharm.2019.01.017

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