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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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General Research Article

Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer

Author(s): Akhlesh Kumar Jain*, Hitesh Sahu, Keerti Mishra and Suresh Thareja

Volume 18, Issue 3, 2021

Published on: 03 September, 2020

Page: [369 - 380] Pages: 12

DOI: 10.2174/1567201817666200903171124

Price: $65

Abstract

Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs) for site-specific delivery.

Background: Liver cancer is the third leading cause of death in the world and the fifth most often diagnosed cancer. It is a major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target-specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of the drug in normal tissues.

Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5- FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs) for effective treatment of liver cancer.

Materials and Methods: 5-FU loaded JFSSNPs were prepared and optimized formulations having higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. The potential of NPs was studied using in vitro cytotoxicity assay, in vivo kinetic studies, and bio-distribution studies.

Result and Discussion: 5-Fluorouracil loaded NPs had a particle size between 336 to 802 nm with drug entrapment efficiency between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of the drug in amorphous form. DSC study suggests there was no physical interaction between 5-FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assisted in the selective accumulation of 5-FU in the liver (vs. other organs spleen, kidney, lungs, and heart) compared to unconjugated one and plain drug.

Conclusion: In vivo, bio-distribution, and plasma profile studies resulted in a significantly higher concentration of 5-Fluorouracil liver, suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

Keywords: 5-Fluorouracil, liver cancer, nanoparticles, Jackfruit seed starch, D-Mannose conjugated nanoparticles, Hep G2 cell lines.

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[1]
Ferlay, J.; Shin, H.R.; Bray, F.; Forman, D.; Mathers, C.; Parkin, D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer, 2010, 127(12), 2893-2917.
[http://dx.doi.org/10.1002/ijc.25516] [PMID: 21351269]
[2]
Chittakath, S.; Puthamohan, V.M.; Shaheen, N.K. In vitro anticancer activity of 5′ fluorouracil coated chitosan nanoparticle. Int. J. Curr. Pharm.Res., 2016, 8(4), 6-8.
[http://dx.doi.org/10.22159/ijcpr.2016v8i4.15267]
[3]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin., 2019, 69(1), 7-34.
[http://dx.doi.org/10.3322/caac.21551] [PMID: 30620402]
[4]
Wang, H.; Lu, Z.; Zhao, X. Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer. J. Hematol. Oncol., 2019, 12(1), 133.
[http://dx.doi.org/10.1186/s13045-019-0806-6] [PMID: 31815633]
[5]
Wilson, B.; Ambika, T.V.; Patel, R.D.; Jenita, J.L.; Priyadarshini, S.R. Nanoparticles based on albumin: preparation, characterization and the use for 5-flurouracil delivery. Int. J. Biol. Macromol., 2012, 51(5), 874-878.
[PMID: 22820011]
[6]
Teo, E.K.; Fock, K.M. Hepatocellular carcinoma: an Asian perspective. Dig. Dis., 2001, 19(4), 263-268.
[http://dx.doi.org/10.1159/000050692] [PMID: 11935085]
[7]
Anwanwan, D.; Singh, S.K.; Singh, S.; Saikam, V.; Singh, R. Challenges in liver cancer and possible treatment approaches. BBA-Rev. Cancer, 2019, pp. 188314.
[8]
GBD 2013 mortality and causes of death collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the global burden of disease study 2013. Lancet, 2015, 385(9963), 117-171.
[http://dx.doi.org/10.1016/S0140-6736(14)61682-2] [PMID: 25530442]
[9]
Center, M.M.; Jemal, A. International trends in liver cancer incidence rates. Cancer Epidemiol. Biomarkers Prev., 2011, 20(11), 2362-2368.
[http://dx.doi.org/10.1158/1055-9965.EPI-11-0643] [PMID: 21921256]
[10]
Wang, Z.; Zhang, G.; Wu, J.; Jia, M. Adjuvant therapy for hepatocellular carcinoma: current situation and prospect. Drug Discov. Ther., 2013, 7(4), 137-143.
[http://dx.doi.org/10.5582/ddt.2013.v7.4.137] [PMID: 24071575]
[11]
de Lope, C.R.; Tremosini, S.; Forner, A.; Reig, M.; Bruix, J. Management of HCC. J. Hepatol., 2012, 56(Suppl. 1), S75-S87.
[http://dx.doi.org/10.1016/S0168-8278(12)60009-9] [PMID: 22300468]
[12]
Aki, F.; Bando, Y.; Takahashi, T.; Uehara, H.; Numoto, S.; Ito, S.; Sasa, M.; Izumi, K. A retrospective study on TS mRNA expression and prediction of the effects of adjuvant oral 5-fluorouracil in breast cancer. Oncol. Lett., 2010, 1(6), 981-987.
[http://dx.doi.org/10.3892/ol.2010.186] [PMID: 22870098]
[13]
Calderini, A.; Pessine, F.B.T.; Franch, G.C. Preparation and characterization of 5-fluorouracil containing PLGA nanospheres coated with chitosan for drug delivery. Int. J. Nanotechnol., 2012, 9, 851-861.
[http://dx.doi.org/10.1504/IJNT.2012.049450]
[14]
Wettergren, Y.; Carlsson, G.; Odin, E.; Gustavsson, B. Pretherapeutic uracil and dihydrouracil levels of colorectal cancer patients are associated with sex and toxic side effects during adjuvant 5-fluorouracil-based chemotherapy. Cancer, 2012, 118(11), 2935-2943.
[http://dx.doi.org/10.1002/cncr.26595] [PMID: 22020693]
[15]
Elias, D.R.; Poloukhtine, A.; Popik, V.; Tsourkas, A. Effect of ligand density, receptor density, and nanoparticle size on cell targeting. Nanomedicine (Lond.), 2013, 9(2), 194-201.
[http://dx.doi.org/10.1016/j.nano.2012.05.015] [PMID: 22687896]
[16]
Jain, A.K.; Thareja, S. In vitro and in vivo characterization of pharmaceutical nanocarriers used for drug delivery. Artif. Cells Nanomed. Biotechnol., 2019, 47(1), 524-539.
[http://dx.doi.org/10.1080/21691401.2018.1561457] [PMID: 30784319]
[17]
Liu, C.; Liu, F.; Feng, L.; Li, M.; Zhang, J.; Zhang, N. The targeted co-delivery of DNA and doxorubicin to tumor cells via multifunctional PEI-PEG based nanoparticles. Biomaterials, 2013, 34(10), 2547-2564.
[http://dx.doi.org/10.1016/j.biomaterials.2012.12.038] [PMID: 23332321]
[18]
Lai, L.F.; Guo, H.X. Preparation of new 5-fluorouracil-loaded zein nanoparticles for liver targeting. Int. J. Pharm., 2011, 404(1-2), 317-323.
[http://dx.doi.org/10.1016/j.ijpharm.2010.11.025] [PMID: 21094232]
[19]
Dangi, R.; Hurkat, P.; Jain, A.; Shilpi, S.; Jain, A.; Gulbake, A.; Jain, S.K. Targeting liver cancer via ASGP receptor using 5- FU-loaded surface-modified PLGA nanoparticles. J. Microencapsul., 2014, 31(5), 479-487.
[http://dx.doi.org/10.3109/02652048.2013.879929] [PMID: 24697169]
[20]
Cheng, M.; He, B.; Wan, T.; Zhu, W.; Han, J.; Zha, B.; Chen, H.; Yang, F.; Li, Q.; Wang, W.; Xu, H.; Ye, T. 5-Fluorouracil nanoparticles inhibit hepatocellular carcinoma via activation of the p53 pathway in the orthotopic transplant mouse model. PLoS One, 2012, 7(10), e47115.
[http://dx.doi.org/10.1371/journal.pone.0047115] [PMID: 23077553]
[21]
Wenfeng, Ni.; Zhengye, Li. Dual-targeting nanoparticles: codelivery of curcumin and5-fluorouracil for synergistic treatment of hepatocarcinoma. J. Pharm. Sci., 2019, 108(3), 1284-1295.
[22]
Mohammad, O.; Faisal, S.M.; Ahmad, N.; Rauf, M.A.; Umar, M.S.; Mujeeb, A.A.; Pachauri, P.; Ahmed, A.; Kashif, M.; Ajmal, M.; Zubair, S. Bio-mediated synthesis of 5-FU based nanoparticles employing orange fruit juice: a novel drug delivery system to treat skin fibrosarcoma in model animals. Sci. Rep., 2019, 9(1), 12288.
[http://dx.doi.org/10.1038/s41598-019-48180-7] [PMID: 31444363]
[23]
Jancy, S.; Shruthy, R.; Preetha, R. Fabrication of packaging film reinforced with cellulose nanoparticles synthesised from jack fruit non-edible part using response surface methodology. Int. J. Biol. Macromol., 2020, 142, 63-72.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.09.066] [PMID: 31521655]
[24]
Chayon, G.; Rakhi, C. Jackfruit (Artocarpus heterophylus) in nutritional composition of fruit cultivars. 2016.
[25]
Hu, J.; Wei, P.; Seeberger, P.H.; Yin, J. Mannose-functionalized nanoscaffolds for targeted delivery in biomedical applications. Chem. Asian J., 2018, 13(22), 3448-3459.
[http://dx.doi.org/10.1002/asia.201801088] [PMID: 30251341]
[26]
Dalle Vedove, E.; Costabile, G.; Merkel, O.M. Mannose and mannose-6-phosphate receptor-targeted drug delivery systems and their application in cancer therapy. Adv. Healthc. Mater., 2018, 7(14), e1701398.
[http://dx.doi.org/10.1002/adhm.201701398] [PMID: 29719138]
[27]
Dutta, H.; Paul, S.K.; Kalita, D.; Mahanta, C.L. Effect of acid concentration and treatment time on acid-alcohol modified jackfruit seed starch properties. Food Chem., 2011, 128(2), 284-291.
[http://dx.doi.org/10.1016/j.foodchem.2011.03.016] [PMID: 25212133]
[28]
Jain, A.K.; Khar, R.K.; Ahmed, F.J.; Diwan, P.V. Effective insulin delivery using starch nanoparticles as a potential trans-nasal mucoadhesive carrier. Eur. J. Pharm. Biopharm., 2008, 69(2), 426-435.
[PMID: 18295464]
[29]
Yalpani, M.; Hall, L.D. Some chemical and analytical aspects of polysaccharides modifications. III. Formation of branched chain, soluble chitosan derivatives. Macromolecules, 1984, 17, 271-282.
[http://dx.doi.org/10.1021/ma00133a003]
[30]
Xibo, M.; Zhen, C.; Yushen, J. SM5-1-conjugated PLA nanoparticles loaded with 5-fluorouracil fortargeted hepatocellular carcinoma imaging and therapy. Biomaterials, 2014, 35(9), 2878-2889.
[31]
Wang, Y.; Li, P.; Chen, L.; Gao, W.; Zeng, F.; Kong, L.X. Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles. Drug Deliv., 2015, 22(2), 191-198.
[http://dx.doi.org/10.3109/10717544.2013.875603] [PMID: 24437926]
[32]
Gupta, A.; Kaur, C.D.; Saraf, S.; Saraf, S. Formulation, characterization, and evaluation of ligand-conjugated biodegradable quercetin nanoparticles for active targeting. Artif. Cells Nanomed. Biotechnol., 2016, 44(3), 960-970.
[PMID: 25813566]
[33]
Chengyun, Y.; Jiwei, G.; Yuzhi, G. In vivo biodistribution for tumour targeting of 5-fluorouracil loaded with N-succinyl-chitosan nanoparticles. Yakugaku Zasshi, 2010, 130(6), 801-804.
[34]
Chaubey, P.; Mishra, B. Mannose-conjugated chitosan nanoparticles loaded with rifampicin for the treatment of visceral leishmaniasis. Carbohydr. Polym., 2014, 101, 1101-1108.
[http://dx.doi.org/10.1016/j.carbpol.2013.10.044] [PMID: 24299880]
[35]
Mandai, T.; Okumoto, H.; Oshitari, T. Synthesis and Biological evaluation of water soluble taxoids bearing sugar moieties. Heterocycles, 2001, 54(2), 561-566.
[http://dx.doi.org/10.3987/COM-00-S(I)34]

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