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Folic Acid Decorated Chitosan Nanoparticles and its Derivatives for the Delivery of Drugs and Genes to Cancer Cells


Affiliations
1 Universiti Teknologi Malaysia, Skudai 81310, Johor, Malaysia
2 2Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City, Viet Nam
3 Department of Chemistry, Bharath Institute of Higher Education and Research, Bharath University, Chennai 600 073, India
4 Department of Physics, Sri Shakthi Institute of Engineering and Technology, Coimbatore 641 062, India
5 Department of Mechanical Engineering, Kongu Engineering College, Erode-638 052, India
6 IJN-UTM Cardiovascular Engineering Centre, Department of Clinical Sciences, Universiti Teknologi Malaysia, Skudai 81300, Johor, Malaysia
 

Nanotechnology offers a number of nanoscale implements for medicine. Among these, nanoparticles are revolutionizing the field of drug and gene delivery. Chitosan is a natural polymer which provides a profitable tool to an innovative delivery system due to its inherent physicochemical and biological characteristics. Chitosan nanoparticles are promising drug and gene delivery carriers because of small size, better stability, low toxicity, inexpensiveness, simplicity, easy fabrication and versatile means of administration. Chitosan can also be easily modified chemically due to the presence of reactive functional hydroxide and amine groups. Folic acid is commonly engaged as a ligand, for targeting cancer cells, as its receptor, that transports folic acid into the cells through endocytosis and is over-expressed on the surface of several human epithelial cancer cells. Integrating folic acid into chitosan-based drug delivery inventions directs the systems with a well-organized targeting ability. The present review outlines several illustrations of this versatile system based on folate decorated chitosan, which have shown potential as auspicious delivery systems published over the past few years. In addition, it is probable to formulate chitosan nanocarriers that exhibit manifold usage beyond targeted delivery, such as nanotheranostics and cancer stem cell therapy.

Keywords

Cancer, Chitosan, Doxorubicin, Drug Delivery, Folic Acid, 5-fluorouracil, Gene Delivery.
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  • https://www.cancer.org/content/dam/cancer-org/research/cancer-factsandstatistics/annual-cancer-facts-and-figures/2017/cancer-facts-andfigures2017.pdf (accessed on 31 May 2017).

  • https://www.cancer.org/treatment/treatments-and-side-effects/treatmenttypes/chemotherapy/how-chemotherapy-drugs-work.html (accessed on 31 May 2017).

  • http://www.understandingnano.com/cancer-treatment-nanotechnology.html (accessed on 31 May 2017).

  • Dand, N. M., Patel, P. B., Ayre, A. P. and Kadam, V. J., Polymeric micelles as a drug carrier for tumour targetting. Chron. Young Sci., 2013, 4, 94–101.

  • Saeed, S. E., Mahnaz, T., Mehdi, F., Javad, M. and Bahram, R., Effects of Levodopa loaded chitosan nanoparticles on cell viability and caspase-3 expression in PC12 neural like cells. Neurosciences, 2013, 18(3), 281–283.

  • Torchilin, V., Tumour delivery of macromolecular drugs based on the EPR effect. Adv. Drug Deliv. Rev., 2011, 63, 131–135.

  • Maeda, H., Macromolecular therapeutics in cancer treatment: the EPR effect and beyond. J. Control Release, 2012, 164, 138–144.

  • Tsume, Y., Hilfinger, J. M. and Amidon, G. L., Enhanced cancer cell growth inhibition by dipeptide prodrugs of floxuridine: increased transporter affinity andmetabolic stability. Mol. Pharm., 2008, 5(5), 717–727.

  • Song, H. et al., Folic acid–chitosan conjugated nanoparticles for improving tumour-targetted drug delivery. BioMed. Res. Int., 2013, 1–6.

  • Lu, Y. and Low, P. S., Folate-mediated delivery of macromolecular anticancer therapeutic agents. Adv. Drug Deliv. Rev., 2002, 54(5), 675–693.

  • Prabaharan, M., Chitosan-based nanoparticles for tumour-targetted drug delivery. Int. J. Biol. Macromolec., 2015, 72, 1313–1322.

  • Agarwal, M., Nagar, D. P., Srivastava, N. and Agarwal, M. K., Chitosan nanoparticles-based drug delivery: an update. Int. J. Adv. Multidiscip. Res., 2015, 2(4), 1–13.

  • Patel, M. P., Patel, R. R. and Patel, J. K., Chitosan mediated targetted drug delivery system: a review. J. Pharm. Pharma. Sci., 2010, 13, 536–557.

  • Jie, J., Wu, W. Z., Zhong, Z. R., Guang, X. T. X., Shu, L. Z. and Wang, L., Recent advances of chitosan nanoparticles. Int. J. Nanomedicine, 2011, 6, 765–774.

  • Wu, J. et al., Chitosan nano carriers loading anti-tumour drugs. J. Nano. Res., 2015, 32, 113–127.

  • Shia, J. et al., Immunohistochemical expression of folate receptoralpha in ovarian epithelial neoplasms bears clinical and pathological significance. Mod. Pathol., 2009, 22, 237a.

  • LeBlanc, J. G., de Giori, G. S., Smid, E. J., Hugenholtz, J. and Sesma, F., Folate production by lactic acid bacteria and other food-grade microorganisms. Current Research and Educational Topics and Trends in Applied Microbiology (ed. Méndez-Vilas, A.), 2007, pp. 329–339.

  • Amidi, M., Mastrobattista, E., Jiskoot, W. and Hennink, W. E., Chitosan-based delivery systems for protein therapeutics and antigens. Adv. Drug Deliv. Rev., 2010, 62(1), 59–82.

  • Prabaharan, M. and Mano, J. F., Chitosan-based particles as controlled drug delivery systems. Drug Deliv., 2005, 12, 41–57.

  • Tiyaboonchai, W. and Limpeanchob, N., Formulation and characterization of amphotericin B-chitosan-dextran sulfate nanoparticles. Int. J. Pharm., 2007, 329, 142–149.

  • Lankalapalli, S. and Kolapalli, V. R. M., Polyelectrolyte complexes: a review of their applicability in drug delivery technology. Indian J. Pharm. Sci., 2009, 71(5), 481–487.

  • Kumar, N., Patel, A. K., Kumari, N. and Kumar, A., A review on chitosan nanoparticles for cancer treatment. Int. J. Nanomater. Bios., 2014, 4(4), 63–65.

  • Huang, H. Y., Shieh, Y. T., Shih, C. M. and Twu, Y. K., Magnetic chitosan/iron (II, III) oxide nanoparticles prepared by spraydrying. Carbohydr Polym., 2010, 81(4), 906–910.

  • Goldberg, M., Langer, R. and Jia, X., Nanostructured materials for applications in drug delivery and tissue engineering. J. Biomater. Sci. Polym. Ed., 2007, 18(3), 241–268.

  • Guaragna, A., Chiaviello, A., Paolella, C., D’Alonzo, D. and Palumbo, G., Synthesis and evaluation of folate-based chlorambucil delivery systems for tumour-targetted chemotherapy. Bioconjug. Chem., 2011, 23(1), 84–96.

  • Vllasaliu, D., Casettari, L., Bonacucina, G., Cespi, M., Palmieri, G. P. and Illum, L., Folic acid conjugated chitosan nanoparticles for tumour targetting of therapeutic and imaging agents, Pharm. Nanotechnol., 2013, 1, 184–203.

  • Chakraborty, S. P., Sahu, S. K., Pramanik, P. and Roy, S., Biocompatibility of folate–modified chitosan nanoparticles. Asian Pac. J. Trop. Biomed., 2012, 2(3), 215–219.

  • Sahu, S. K., Maiti, S., Maiti, T. K., Ghosh, S. K. and Pramanik, P., Folate-decorated succinylchitosan nanoparticles conjugated with doxorubicin for targetted drug delivery. Macromol. Biosci., 2011, 11(2), 285–295.

  • Jiang, H. L. et al., The suppression of lung tumourigenesis by aerosol-delivered folatechitosan-graft-polyethylenimine/Akt1 shRNA complexes through the Akt signalling pathway. Biomater., 2009, 30(29), 5844–5852.

  • Bhattacharya, S., Li, X., Nyshadham, J. and Jasti, B., Folate receptor targetted delivery systems: a novel micellar drug delivery approach. Curr. Trends Biotechnol. Pharm., 2010, 4(1), 490–509.

  • Ke, J. H., Lin, J. J., Carey, J. R., Chen, J. S., Chen, C. Y. and Wang, L. F., A specific tumour-targetting magnetofluorescent nanoprobe for dual-modality molecular imaging. Biomaterials, 2010, 31, 1707–1715.

  • Bahrami, B. et al., Folate-conjugated nanoparticles as a potent therapeutic approach in targetted cancer therapy. Tumour Biol., 2015, 36(8), 5727–5742.

  • Park, J. H., Lee, S., Park, K., Kim, K. and Kwan, I. C., Smart chitosanbased stimuli-responsive nanocarriers for the controlled delivery of hydrophobic pharmaceuticals. Macromolecules. 2011, 44, 1298–1302.

  • Neha, M. D., Pranav, B. P., Anita, A. and Vilasrau, J. K., Polymeric micelles as a drug carrier for tumour targetting. Chron. Young Sci., 2013, 4(2), 94–101.

  • Goren, D., Horowitz, A. T., Tzemach, D., Tarshish, M., Zalipsky, S. and Gabizon, A., Nuclear delivery of doxorubicin via folatetargetted liposomes with bypass of multidrug-resistance efflux pump. Clin. Cancer Res., 2000, 6(5), 1949–1957.

  • Yang, H. C. and Hon, M. H., The effect of the molecular weight of chitosan nanoparticles and its application on drug delivery. Microchem. J., 2009, 92(1), 87–91.

  • Parveen, S. and Sahoo, S. K., Evaluation of cytotoxicity and mechanism of apoptosis of doxorubicin using folate-decorated chitosan nanoparticles for targetted delivery to retinoblastoma. Cancer Nanotechnol., 2010, 1(1–6), 47–62.

  • Fan, L. et al., Co-delivery of PDTC and doxorubicin by multifunctional micellar nanoparticles to achieve active targetted drug delivery and overcome multidrug resistance. Biomaterials, 2010, 31(21), 5634–5642.

  • Shen, J. M., Tang, W. J., Zhang, X. L., Chen, T. and Zhang, H. X., A novel carboxymethyl chitosan-based folate/Fe3O4/CdTe nanoparticle for targetted drug delivery and cell imaging. Carbohydr. Polym., 2012, 88(1), 239–249.

  • Hu, H., Tang, C. and Yin, C., Folate conjugated trimethylchitosan/ graphene oxide nanocomplexes as potential carriers for drug and gene delivery. Mater Lett., 2014, 125, 82–85.

  • Yu, J. et al., Folic acid conjugated glycol chitosan micelles for targetted delivery of doxorubicin: preparation and preliminary evaluation in vitro. J. Biomater. Sci. Polym. Ed., 2013, 24(5), 606–620.

  • Chen, D. et al., pH responsive mechanism of a deoxycholic acid and folate comodified chitosan micelle under cancerous environment. J. Phys. Chem. B, 2013, 117(5), 1261–1268.

  • Manaspon, C., Viravaidya-Pasuwat, K. and Pimpha, N., Preparation of folate-conjugated pluronic f127/chitosan core-shell nanoparticles encapsulating doxorubicin for breast cancer treatment. J. Nanomater., 2012, 2012, 1–11.

  • Depan, D., Shah, J. and Misra, R. D. K., Controlled release of drug from folate-decorated and graphene mediated drug delivery system: Synthesis, loading efficiency, and drug release response. Mater. Sci. Eng. C, 2011, 31(7), 1305–1312.

  • Huang, H., Yuan, Q., Shah, J. S. and Misra, R. D. K., A new family of folate decorated carbon nanotube-mediated drug delivery system: synthesis and drug delivery response. Adv. Drug Deliv. Rev., 2011, 63(14–15), 1332–1339.

  • Lee, K. D., Choi, S. H., Kim, D. H., Lee, H. Y. and Choi, K. C., Self-organized nanoparticles based on chitosan-folic acid and dextran succinate-doxorubicin conjugates for drug targetting. Arch. Pharm. Res., 2014, 37, 1546–1553.

  • Ji, Z. et al., Targeted therapy of SMMC-7721 liver cancer in vitro and in vivo with carbon nanotubes based drug delivery system. J. Colloid Interf. Sci., 2012, 365(1), 143–149.

  • Wang, Y., Li, P., Chen, L., Gao, W., Zeng, F. and 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.

  • Mathew, M. E., Mohan, J. C., Manzoor, K., Nair, S. V., Tamura, H. and Jayakumar, R., Folate conjugated carboxymethyl chitosan manganese doped zinc sulphide nanoparticles for targetted drug delivery and imaging of cancer cells. Carbohydr. Polym., 2010, 80(2), 443–449.

  • Kadagi, M. et al., Synthesis, characterisation of 5-Fu loaded chitosan nanoparticles, Glob. J. Res. Anal., 2014, 3(9), 114–116.

  • Yu, S. et al., Inorganic nanovehicle for potential targetted drug delivery to tumour cells, tumour optical imaging, ACS Appl. Mater. Interf., 2015, 7, 5089–5096.

  • Li, H. L., He, Y. X., Gao, Q. H. and Wu, G. H., Folatepolyethylene glycol conjugated carboxymethyl chitosan for tumour-targetted delivery of 5-fluorouracil. Mol. Med. Rep., 2014, 9, 786–792.

  • Yang, Z. M., Peng, Z. and Zhou, M., Drug-loading chitosan polymer microsphere with targetted and slow-release function and its characteristics. J. Funct. Mat., 2013, 44(12), 1703–1708.

  • Blanco, M. D., Guerrero, S. and Benito, M., In vitro and in vivo evaluation of a folate-targetted copolymeric submicrohydrogel based on n-isopropylacrylamide as 5-fluorouracil delivery system. Polym., 2011, 3, 1107–1125.

  • Vasanti, S. and Preeti, S., Paclitaxel nanoparticles – an approach to improve the bioavailability. Int. J. Pharm. Sci. Rev. Res., 2014, 27(1), 200–208.

  • You, J., Li, X., De Cui, F., Du, Y. Z., Yuan, H. and Hu, F. Q., Folate-conjugated polymer micelles for active targetting to cancer cells: preparation, in vitro evaluation of targetting ability and cytotoxicity. Nanotechnol., 2008, 19(4), 1–9.

  • Lan, G. J., Sen-ming, W., Xi-gang, H., Man-ming, C. A. O. and Ji-ren, Z., Synthesis and characterization of folic acid-conjugated chitosan nanoparticles as a tumour-targetted drug carrier. J. South Med. Univ., 2008, 28(12), 2183–2186.

  • Qu, D., Lin, H., Zhang, N., Xue, J. and Zhang, C., In vitro evaluation on novel modified chitosan for targetted antitumour drug delivery. Carbohydr. Polym., 2013, 92(1), 545–554.

  • Wang, F. et al., Tissue distribution and pharmacokinetics evaluation of DOMC-FA micelles for intravenous delivery of PTX. J. Drug Deliv., 2013, 21(2), 137–145.

  • Huang, S., Wan, Y., Wang, Z. and Wu, J., Folate-conjugated chitosan– polylactide nanoparticles for enhanced intracellular uptake of anticancer drug. J. Nanopart. Res., 2013, 15, 1–15.

  • Sahu, S. K., Maiti, S., Maiti, T. K., Ghosh, S. K. and Pramanik, P., Hydrophobically modified carboxymethyl chitosan nanoparticles targetted delivery of paclitaxel. J. Drug Target, 2011, 19(2), 104–113.

  • Hou, Z. et al., Both FA- and mPEG-conjugated chitosan nanoparticles for targetted cellular uptake and enhanced tumour tissue distribution. Nanoscale Res. Lett., 2011, 6(1), 563–574.

  • Jia, M., Li, Y. and Yang, X., Development of both methotrexate and mitomycin c loaded pegylated chitosan nanoparticles for targetted drug codelivery and synergistic anticancer effect. Appl. Mater. Interfaces, 2014, 6, 11413–11423.

  • Patel, M. P., Patel, R. R. and Patel, J. K., Chitosan mediated targetted drug delivery system: a review. J. Pharm. Pharmaceut. Sci., 2010, 13(3), 536–557.

  • Lin, J., Li, Y. and Wu, H., Tumour-targetted co-delivery of mitomycin C and 10-hydroxycamptothecin via micellar nanocarriers for enhanced anticancer efficacy. RSC Adv., 2015, 5, 23022–23033.

  • Li, Y., Wu, H. and Jia, M., Therapeutic effect of folate-targetted and pegylated phytosomes loaded with a Mitomycin C-soybean phosphatidyhlcholine complex. Mol. Pharmaceu., 2014, 11, 3017–3026.

  • Morris, V. B., Pillai, C. K. S. and Sharma, C. P., Folic acid conjugated depolymerized quaternized chitosan as potential targetted gene delivery vector. Polym. Int., 2011, 60(7), 1097–106.

  • Zhou, Y., Chen, J. and Wang, H., Synthesis and characterization of folate-poly(ethylene glycol) chitosan graft-polyethylenimine as a non-viral carrier for tumour-targetted gene delivery. Afr. J. Biotechnol., 2011, 10(32), 6120–6129.

  • Kim, Y. K., Tehrani, A. M., Lee, J. H., Cho, C. S., Cho, M. H. and Jiang, H. L., Therapeutic efficiency of folated poly(ethylene glycol)chitosan-graft-polyethylenimine-Pdcd4 complexes in H-ras12V mice with liver cancer. Int. J. Nanomed., 2013, 8, 1489–1498.

  • Gaspar, V. M., Costa, E. C., Queiroz, J. A., Pichon, C., Sousa, F. and Correia, I. J., Folate-targetted multifunctional amino acidchitosan nanoparticles for improved cancer therapy. Pharm. Res., 2015, 32, 562–577.

  • Guana, Q. and Wang, M., Fabrication and characteristics of genedelivering nanodevices based on Au-Ag@CS-FA hybrid particles. Mater. Sci. Forum, 2015, 815, 401–406.

  • Lai, W. F. and Lin, M. C., Folate-conjugated chitosanpoly( ethylenimine) copolymer as an efficient and safe vector for gene delivery in cancer cells. Curr. Gene Ther., 2015, 15(5), 472– 480.

  • Yan, C. Y., Gu, J. W. and Hou, D. P., Synthesis of tat tagged and folate modified N-succinyl-chitosan self-assembly nanoparticles as a novel gene vector. Int. J. Biol. Macromol., 2015, 72, 751–756.

  • Shi, B., Zhang, H., Bi, J. and Dai, S., Endosomal pH responsive polymers for efficient cancer targetted gene therapy. Colloids Surf. B, 2014, 119, 55–65.

  • Li, T. S., Yawata, T. and Honke, K., Efficient siRNA delivery and tumour accumulation mediated by ionically cross-linked folic acid-poly(ethylene glycol)-chitosan oligosaccharide lactate nanoparticles: for the potential targetted ovarian cancer gene therapy. Eur. J. Pharm. Sci., 2014, 52, 48–61.

  • Yu, B., Tang, C. and Yin, C., Enhanced antitumour efficacy of folate modified amphiphilic nanoparticles through co-delivery of chemotherapeutic drugs and genes. Biomaterials, 2014, 35(24), 6369–6378.

  • Wang, M., Hu, H. and Sun, Y., A pH-sensitive gene delivery system based on folic acid-PEG-chitosan-PAMAM-plasmid DNA complexes for cancer cell targetting. Biomaterials, 2013, 34(38), 10120–10132.

  • Zheng, Y., Song, X. and He, G., Receptor-mediated gene delivery by folate-poly(ethylene glycol)-grafted-trimethyl chitosan in vitro. J. Drug Target, 2011, 19(8), 647–656.

  • Parker, N., Turk, M. J., Westrick, E., Lewis, J. D., Low, P. S. and Leamon, C. P., Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal. Biochem., 2005, 338, 284–293.

  • Bwatanglang, I. B., Mohammad, F. and Yusof, N. A., Folic acid targetted Mn : ZnS quantum dots for theranostic applications of cancer cell imaging and therapy. Int. J. Nanomed., 2016, 11, 413–428.


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  • Folic Acid Decorated Chitosan Nanoparticles and its Derivatives for the Delivery of Drugs and Genes to Cancer Cells

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Authors

Agnes Aruna John
Universiti Teknologi Malaysia, Skudai 81310, Johor, Malaysia
Saravana Kumar Jaganathan
2Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City, Viet Nam
Manikandan Ayyar
Department of Chemistry, Bharath Institute of Higher Education and Research, Bharath University, Chennai 600 073, India
Navaneetha Pandiyaraj Krishnasamy
Department of Physics, Sri Shakthi Institute of Engineering and Technology, Coimbatore 641 062, India
Rathanasamy Rajasekar
Department of Mechanical Engineering, Kongu Engineering College, Erode-638 052, India
Eko Supriyanto
IJN-UTM Cardiovascular Engineering Centre, Department of Clinical Sciences, Universiti Teknologi Malaysia, Skudai 81300, Johor, Malaysia

Abstract


Nanotechnology offers a number of nanoscale implements for medicine. Among these, nanoparticles are revolutionizing the field of drug and gene delivery. Chitosan is a natural polymer which provides a profitable tool to an innovative delivery system due to its inherent physicochemical and biological characteristics. Chitosan nanoparticles are promising drug and gene delivery carriers because of small size, better stability, low toxicity, inexpensiveness, simplicity, easy fabrication and versatile means of administration. Chitosan can also be easily modified chemically due to the presence of reactive functional hydroxide and amine groups. Folic acid is commonly engaged as a ligand, for targeting cancer cells, as its receptor, that transports folic acid into the cells through endocytosis and is over-expressed on the surface of several human epithelial cancer cells. Integrating folic acid into chitosan-based drug delivery inventions directs the systems with a well-organized targeting ability. The present review outlines several illustrations of this versatile system based on folate decorated chitosan, which have shown potential as auspicious delivery systems published over the past few years. In addition, it is probable to formulate chitosan nanocarriers that exhibit manifold usage beyond targeted delivery, such as nanotheranostics and cancer stem cell therapy.

Keywords


Cancer, Chitosan, Doxorubicin, Drug Delivery, Folic Acid, 5-fluorouracil, Gene Delivery.

References





DOI: https://doi.org/10.18520/cs%2Fv113%2Fi08%2F1530-1542