A New Approach To The Treatment of Leıshmaniasis: Quercetin-Loaded Polycaprolactone Nanoparticles

Year 2018, Volume: 5 Issue: 3, 1071 - 1082, 01.09.2018

Emrah Şefik Abamor

https://doi.org/10.18596/jotcsa.417831

Cited By: 7

Abstract

Antileishmanial drugs used in the treatment of leishmaniasis
are toxic and expensive. Moreover, parasites have recently developed resistance
against them. Hence there is an increasing need for developing new
antileishmanial medicines. Quercetin, found in the roots, leaves and fruits of
many plants, is a natural polyphenolic flavonoid. Quercetin has antibacterial,
antiviral, anti-carcinogenic, and antioxidant properties. On the other hand,
because of its weak solubility in water, quercetin has had limited use on
humans. To increase its bio-availability and maximize its therapeutic effects,
quercetin has recently been encapsulated with nanoparticulate carrier systems.
The aim of this study is to encapsulate quercetin in bio-degradable,
bio-compatible poly-ε-caprolactone (PCL) nanoparticles, to characterize the
synthesized nanoparticles and to analyze their in vitro antileishmanial
efficacy on L.infantum parasites. Quercetin-loaded PCL nanoparticles (QPNPs)
were synthesized using oil-in-water single emulsion solvent evaporation method.
Their characterization was done using scanning electron microscopy (SEM) and
dynamic light scattering (DLS) equipments. Encapsulation effectiveness and release
profiles of QPNPs are calculated with UV-Vis spectrophotometry. The
antileishmanial effectiveness of the synthesized nanoparticles was analyzed in
L.infantum promastigote culture and amastigote-macrophage culture. The results
indicated that QPNPs had an average size of 380 nm, a zeta potential of -6.56
mV, and a PDI value of 0.21. The measurements showed the quercetin-loaded
nanoparticles to have an encapsulation effectiveness of 64% and a reaction
efficiency of 55%. After an incubation of 192 hours, nanoparticles were seen to
release 58% of their quercetin content. The synthesized QPNPs had IC50 values
on L.infantum promastigotes and amastigotes of 86 and 144 µg/mL respectively.
This means that QPNPs have reduced the vitality of promastigotes about 20 times
and of amastigotes about 5 times as compared to the control group. These
results demonstrate the strong antileishmanial potentials of QPNPs. It is
believed that if these positive findings are supported by further in vivo
studies, QPNPs may be used in the treatment of leishmaniasis.

Keywords

Leishmania, quercetin, polycaprolactone, nanoparticles

References

• 1. Vannier-Santos MA, Martiny A, de Souza W. Cell biology of Leishmania spp.: invading and evading. Curr Pharm Des. 2002;8(4):297-318.
• 2. de Vries HJ, Reedijk SH, Schallig HD. Cutaneous leishmaniasis: recent developments in diagnosis and management. Am J Clin Dermatol. 2015;16(2):99-109.
• 3. Bailey MS, Lockwood DN. Cutaneous leishmaniasis. Clin Dermatol. 2007;25(2):203-11.
• 4. Torres-Guerrero E, Quintanilla-Cedillo MR, Ruiz-Esmenjaud J, Arenas R. Leishmaniasis: a review. F1000Res. 2017;6:750.
• 5. Reithinger R, Dujardin JC, Louzir H, Pirmez C, Alexander B, Brooker S.Cutaneous leishmaniasis. Lancet Infect Dis. 2007;7(9):581-96.
• 6. Bravo F, Sanchez MR. New and re-emerging cutaneous infectious diseases in Latin America and other geographic areas. Dermatol Clin. 2003;21(4):655-68
• 7. Gurunath U, Joshi R, Agrawal A, Shah V. An overview of visceral leishmaniasis elimination program in India: a picture imperfect. Expert Rev Anti Infect Ther.2014;12(8):929-35.
• 8. González C, Wang O, Strutz SE, González-Salazar C, Sánchez-Cordero V, Sarkar S. Climate change and risk of leishmaniasis in north america: predictions from ecological niche models of vector and reservoir species. PLoS Negl Trop Dis. 2010;4(1):e585.
• 9. Stamm LV. Human Migration and Leishmaniasis-On the Move. JAMA Dermatol. 2016;152(4):373-4.
• 10. Singh OP, Singh B, Chakravarty J, Sundar S. Current challenges in treatment options for visceral leishmaniasis in India: a public health perspective. Infect Dis Poverty. 2016;5:19.
• 11. Moore EM, Lockwood DN. Treatment of visceral leishmaniasis. J Glob Infect Dis. 2010;2(2):151-8.
• 12. Chakravarty J, Sundar S. Drug resistance in leishmaniasis. J Glob Infect Dis. 2010;2(2):167-76.
• 13. Ekor M. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol. 2014;4:177.
• 14. Anand David AV, Arulmoli R, Parasuraman S. Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid. Pharmacogn Rev. 2016;10(20):84-89.
• 15. Salvamani S, Gunasekaran B, Shaharuddin NA, Ahmad SA, Shukor MY. Antiartherosclerotic effects of plant flavonoids. Biomed Res Int. 2014;2014:480258.
• 16. Sultana B, Anwar F. Flavonols (kaempeferol, quercetin, myricetin) contents of selected fruits, vegetables and medicinal plants. Food Chem. 2008;108(3):879-84.
• 17. Moalin M, Strijdonck GP, Beckers M, Hagemen G, Borm P, Bast A, Haenen GR. A planar conformation and the hydroxyl groups in the B and C rings play a pivotal role in the antioxidant capacity of quercetin and quercetin derivatives. Molecules. 2011;16(11):9636-50.
• 18. Kumari A, Yadav SK, Pakade YB, Singh B, Yadav SC. Development of biodegradable nanoparticles for delivery of quercetin. Colloids Surf B Biointerfaces. 2010;80(2):184-92.
• 19. Natarajan V, Krithica N, Madhan B, Sehgal PK. Formulation and evaluation of quercetin polycaprolactone microspheres for the treatment of rheumatoid arthritis. J Pharm Sci. 2011 Jan;100(1):195-205.
• 20. McNeil SE, Griffiths HR, Perrie Y. Polycaprolactone fibres as a potential delivery system for collagen to support bone regeneration. Curr Drug Deliv. 2011;8(4):448-55.
• 21. Madhaiyan K, Sridhar R, Sundarrajan S, Venugopal JR, Ramakrishna S. Vitamin B12 loaded polycaprolactone nanofibers: a novel transdermal route for the water soluble energy supplement delivery. Int J Pharm. 2013 Feb 28;444(1-2):70-6.
• 22. Ma Y, Zheng Y, Zeng X, Jiang L, Chen H, Liu R, Huang L, Mei L. Novel docetaxel-loaded nanoparticles based on PCL-Tween 80 copolymer for cancer treatment. Int J Nanomedicine. 2011;6:2679-88.
• 23. de Menezes JP, Guedes CE, Petersen AL, Fraga DB, Veras PS. Advances in Development of New Treatment for Leishmaniasis. Biomed Res Int. 2015;2015:815023.
• 24. Nam JS, Sharma AR, Nguyen LT, Chakraborty C, Sharma G, Lee SS. Application of Bioactive Quercetin in Oncotherapy: From Nutrition to Nanomedicine. Molecules. 2016;21(1):E108.
• 25. Johari J, Kianmehr A, Mustafa MR, Abubakar S, Zandi K. Antiviral activity of baicalein and quercetin against the Japanese encephalitis virus. Int J Mol Sci.2012;13(12):16785-95.
• 26. Ramos FA, Takaishi Y, Shirotori M, Kawaguchi Y, Tsuchiya K, Shibata H, Higuti T, Tadokoro T, Takeuchi M. Antibacterial and antioxidant activities of quercetin oxidation products from yellow onion (Allium cepa) skin. J Agric Food Chem. 2006;54(10):3551-7.
• 27. Arasoglu T, Derman S, Mansuroglu B, Uzunoglu D, Kocyigit B, Gumus B, Acar T, Tuncer B. Preparation, characterization, and enhanced antimicrobial activity: quercetin-loaded PLGA nanoparticles against foodborne pathogens. Turk J Biol. 2017;41:p127-140.
• 28. Zheng D, Li X, Xu H, Lu X, Hu Y, Fan W. Study on docetaxel-loaded nanoparticles with high antitumor efficacy against malignant melanoma. Acta Biochim Biophys Sin (Shanghai). 2009 Jul;41(7):578-587
• 29. Rachmawati H, Yanda YL, Rahma A, Mase N. Curcumin-Loaded PLA Nanoparticles: Formulation and Physical Evaluation. Sci Pharm. 2016 Feb 14;84(1):191-202.
• 30. Li B, Li Q, Mo J, Dai H. Drug-Loaded Polymeric Nanoparticles for Cancer Stem Cell Targeting. Front Pharmacol. 2017 Feb 14;8:51.
• 31. Kalluru R, Fenaroli F, Westmoreland D, Ulanova L, Maleki A, Roos N, Paulsen Madsen M, Koster G, Egge-Jacobsen W, Wilson S, Roberg-Larsen H, Khuller GK, Singh A, Nyström B, Griffiths G. Poly(lactide-co-glycolide)-rifampicin nanoparticles efficiently clear Mycobacterium bovis BCG infection in macrophages and remain membrane-bound in phago-lysosomes. J Cell Sci. 2013;126(14):3043-54.
• 32. Danafar H, Schumacher U. MPEG–PCL copolymeric nanoparticles in drug delivery systems. Cogent Medicine. 2016;3:1
• 33. Pathak M, Coombes AGA, Ryu B, Cabot PJ, Turner MS, Palmer C, Wang D, Steadman KJ. Sustained Simultaneous Delivery of Metronidazole and Doxycycline From Polycaprolactone Matrices Designed for Intravaginal Treatment of Pelvic Inflammatory Disease. J Pharm Sci. 2018;107(3):863-869.
• 34. Belkhelfa-Slimani R, Djerdjouri B. Caffeic acid and quercetin exert caspases-independent apoptotic effects on Leishmania major promastigotes, and reactivate the death of infected phagocytes derived from BALB/c mice. Asian Pacific Journal of Tropical Biomedicine. 2017;7(4):321-331
• 35. Fonseca-Silva F, Inacio JD, Canto-Cavalheiro MM, Almeida-Amaral EE. Reactive oxygen species production and mitochondrial dysfunction contribute to quercetin induced death in Leishmania amazonensis. PLoS One. 2011;6(2):e14666.
• 36. Kheirandish F, Delfan B, Mahmoudvand H, Moradi N, Ezatpour B, Ebrahimzadeh F, Rashidipour M. Antileishmanial, antioxidant, and cytotoxic activities of Quercus infectoria Olivier extract. Biomed Pharmacother. 2016;82:208-15.
• 37. Sun D, Li N, Zhang W, Yang E, Mou Z, Zhao Z, Liu H, Wang W. Quercetin-loaded PLGA nanoparticles: a highly effective antibacterial agent in vitro and anti-infection application in vivo. J Nanopart Res. 2016;18:1-21.