Frontiers in Biomedical Sciences
Articles Information
Frontiers in Biomedical Sciences, Vol.1, No.2, Nov. 2016, Pub. Date: Jan. 9, 2017
The Chemical Approach of Methotrexate Targeting
Pages: 50-73 Views: 5468 Downloads: 2187
Authors
[01] Loay Abdulrahman, Chemistry Department, Howard University, Washington DC, USA.
[02] Oladapo Bakare, Chemistry Department, Howard University, Washington DC, USA.
[03] Maiada Abdulrahman, Department of Health, Stratford University, Alexandria, USA.
Abstract
“Cancer is the second most deadly disease that kills half a million Americans each year, the first being heart diseases. National Center for health statistics from the year 2009 shows that as many as 1,555 people die each day of some cancer” [1]. Around the world the discovery and development of anticancer agent become the key focus of several pharmaceutical companies and organizations which invested in prevention, diagnosis, and treatment of this disease. Methotrexate (MTX) has used for many years in the treatment of patients with cancer as a cytotoxic agent and as an anti-inflammatory drug for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA). The objective of this article is to produce an update and review the amount of effort in developing a new candidate of this clinically used the drug to minimize the side effect and enhance the therapeutic index. Researchers have linked MTX to various polymeric drug carriers. Coupled MTX led to the incorporation of medication with different modes of toxicity towards the healthy tissue. Proposal for the new candidate of this new drug suggested, with high precision and low advers effect, the scientists say, the conjugates could make cancer drugs already on the market more efficient and give new life to cancer drugs that shelved for being too toxic.
Keywords
Methotrexate, PEGylated MTX, Dendrimer, Polysaccharide, Nanoparticles, Carbon Based Nanotubes, Nanocage Protein
References
[01] Gottesman MM. Mechanisms of cancer drug resistance. Ann Rev Med 2002; 53: 615–27.
[02] Abali EE, Skacel NE, Celikkaya H, Hsieh YC. Regulation of human dihydrofolate reductase activity and expression. Vitamin and Hormone 79: 267-287.
[03] Schnell JR, Dyson HJ, Wright PE. Structure dynamics, and catalytic function of dihydrofolate reductase. Ann Rev Biophys Biomol struct 2004; 33: 119-140.
[04] Abdulrahman L, Chhabra SR. The Chemistry of Methotrexate. Med Res Rev 1988; 8: 95-155.
[05] Rosowsky A, Beardsley GP, Ensminger WD, Lazarus H, Yu CS. Methotrexate analogs 11. Unambiguous chemical synthesis and in vitro biological evaluation of alpha- and gamma-monoesters as potential prodrugs. J Med Chem 1978; 21: 380–386.
[06] Jerry BH, George P. Protein Design and the Development of New Therapeutics and Vaccines. Plenium press, NY 1990: 307
[07] Bavetsias V, Jackman AL, Marriott JH, Kimbell R, Gibson W, Boyle FT, Bisset GM. Folate-based inhibitors of thymidylate synthase. J Med Chem 1997; 40: 1495-1510.
[08] Gangjee A, Yang J, McGuire JJ, Kisliuk RLSynthesis and evaluation of a classical 2,4-diamino-5-substituted-furo[2,3-d]pyrimidine and a 2-amino-4-oxo-6-substituted-pyrrolo[2,3-d]pyrimidine as antifolates. Bioorg & Med Chem 2006; 14: 8590-8598.
[09] Gangjee A, Devraj R, McGuire JJ, Kisliuk RL. Effect of bridge region variation on antifolate and antitumor activity of classical 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines. J Med Chem 1995; 38: 3798.
[10] Gangjee A, Devraj R, McGuire JJ, Kisliuk RL, Queener SF, Barrows LR. Classical and Nonclassical Furo[2,3-d]pyrimidines as Novel Antifolates: Synthesis and Biological Activities J Med Chem 1994; 37: 1169.
[11] Gangjee A, Zeng Y, McGuire JJ, Kisliuk RL. Synthesis and antifolate properties of 10-alkyl-8,10-dideazaminopterins. J Med Chem 2000; 43: 3125.
[12] Lu YH, Gao XQ, Wu M, Zhang-Negrerie D, Gao Q. Strategies on the development of small molecule anticancer drugs for targeted therapy. Mini Rev Med Chem. 2011; 11: 611-24.
[13] David A. Gewirtz, A. Critical Evaluation of the Mechanisms of Action Proposed for the Antitumor Effects of the Anthracycline Antibiotics Adriamycin and Daunorubicin, Biochemical Pharmacology 1999; 57: 727–741.
[14] Baskar R, Lee KA, Yeo R, Yeoh KW. Cancer and Radiation Therapy: Current Advances and Future Directions. Int J Med Sci 2012; 9: 193-199.
[15] Li Y, Haiqing D, Li X, Shi D, Li Y. Single Polymer-drug Conjugate Carrying Two Drugs for Fixed-dose Codelivery. Med chem 2014; 4: 676-683.
[16] William BL, David RK, Brandon VS, Nicholas AP. Polymers for Drug Delivery Systems. Ann Rev Chem Biomol Eng 2010; 1: 149–173.
[17] Webster R, Didier E, Harris P, Siegel N, Stadler J, Tilbury L, Smith D. PEGylated proteins: Evaluation of their safety in the absence of definitive metabolism studies. Drug Metab Dispos 2007; 35: 9–16.
[18] Pasut G, Sergi M, Veronese FM. Anti-cancer PEG-enzymes: 30 years old, but still a current approach. Adv Drug Deliv Rev 2008; 60: 69–78.
[19] Ryan SM, Mantovani G, Wang X, Haddleton DM, Brayden DJ. Advances in PEGylation of important biotech molecules: delivery aspects. Expert Opin Drug Deliv 2008; 5: 371–383.
[20] Haiqing D, Chunyan D, Wenjuan X, Yongyong L, Tianbin R. Self-assembled, redox-sensitive, H-shaped pegylated methotrexate conjugates with high drug-carrying capability for intracelular drug delivery. Med Chem Commun 2014; 5: 147-152.
[21] Riebeseel K, Biedermann E, Lӧser R, Breiter N, Hanselmann R, Muelhaupt R, Unger C, Kratz F. Polyethylene glycol conjugate of MTX varying in molecular weight from MW 750 to MW 40.000: synthesis, characterization and structure activity relationships in vitro and in vivo. Bioconj Chem 2002; 13: 773-785.
[22] Gholamhossein Y, Seyed M F, Afshin Z, Alireza S. Synthesis and Characterization of Methotrexate Polyethylene Glycol Esters as a Drug Delivery System. Chem Pharm Bull 2010; 58: 147-153.
[23] Divya BB. Pegylated methotrexate based micellar conjugates for anticancer chemotherapy. Asian J Parmaceutics 2015; 9: 69-82.
[24] Fanghong L, Yang L, Mengmeng J, Fei C, Hongjie W, Fei Y, Jinyan L, Xiangrui Y, Zhenqing H, Qiqing Z. Validation of a Janus role of methotrexate-based PEGylated chitosan nanoparticles in vitro. Nanoscale Res Letters 2014; 9: 363.
[25] Chetana DM, Suketu JP, Alpesh BD, Murthy RSR. Functionalization and evaluation of PEGylated Carbon Nanotubes as novel Drug delivery for methotrexate. J Appl Pharm Sci 2011; 1: 103-108.
[26] W Li, P Zhan, ED Clercq, H Lou, X Liu. Current drug research on PEGylation with small molecular agents. Prog Poly Sci 2013; 38: 421-444.
[27] Newkome GR, Yao ZQ, Baker GR, Gupta VK. Micelles. Part 1. Cascade molecules: a new approach to micelles A [27]-arborol. J Org Chem 1985; 50: 2003-2004.
[28] Duncan R, Dimitrijevic S, Evagorou EG. The Role of Polymer Conjugates in the Diagnosis and Treatment of Cancer. STP Pharma Sci 1996; 6: 237-263.
[29] Maeda H, Seymour LW, Miyamoto Y. Conjugates of Anticancer Agents and Polymers: Advantages of Macromolecular Therapeutics in Vivo. Bioconj Chem 1992; 3: 351-362.
[30] Mehvar R. Dextrans for Targeted and Sustained Delivery of Therapeutic and Imaging Agents. J Control Release 2000; 69: 1-25.
[31] Matsumura RB, Maeda H. A New Concept for Macromolecular Therapeutics in Cancer Chemotherapy: Mechanism of Tumoritropic Accumulation of Proteins and the Antitumor Agent SMANCS. Cancer Res 1986; 46: 6387-6392.
[32] Ellens H, Bentz J, Szoka FC. H+-Induced and Ca-2+-Induced Fusion and Destabilization of Liposomes. Biochem 1985; 24: 3099-3106.
[33] Watkins DM, Sayed-Sweet Y, Klimash JW, Turro NJ, Tomalia DA. Dendrimers with hydrophobic cores and the formation of supramolecular dendrimersurfactant assemblies. Langmuir 1997; 12: 3136-3141.
[34] Hawker CJ, Wooley KL, Fre´chet JMJ. Unimolecular Micelles and Globular Amphiphiles - Dendritic Macromolecules as Novel Recyclable Solubilization Agents. J Chem Soc Perkin Trans 1 1993; 12: 1287-1297
[35] Tomalia DA, Baker H, Dewald J, Hall M, Kallos G, Martin S, Roeck J, Ryder J, Smith P. A New Class of Polymers-Starburst-Dendritic Macromolecules. Polym J 1985; 17: 117-132.
[36] Haensler J, Szoka FCJr. Poliamidoamine Cascade Polymers Mediate Efficient Transfection of Cells in Culture. Bioconj Chem 1993; 4: 372-379.
[37] Malik N, Wiwattanapatapee R, Klopsch R, Lorenz K, Frey H, Weener JW, Meijer EW, Paulus W, Duncan R. Dendrimers: Relationship Between Structure and Biocompatibility in Vitro, and Preliminary Studies on the Biodistribution of 125I-Labeled Polyamidoamine Dendrimers in Vivo. J Control Release 2000; 65: 133-148.
[38] Supattapone S, Wille H, Uyechi L, Safar J, Tremblay P, Szoka FCJr, Cohen FE, Prusiner SB, Scott MR. Branched Polyamines Cure Prion-Infected Neuroblastoma Cells. J Virol 2001; 75: 3453-3461.
[39] Duncan R, Malik N. Dendrimers: Biocompatibility and Potential for Delivery of Anticancer Agents. Proc Int Symp Controlled Release Bioact Mater 1996; 23: 105-106.
[40] Jolanta FKL, Kimberly AC, Zhengyi C, Shraddha SN, Istvan JM, Thommey PT, Lajos PB, Mohamed KK. Nanoparticle Targeting of Anticancer Drug Improves Therapeutic Response in Animal Model of Human Epithelial Cancer. Cancer Res 2005; 65: 5317-5324.
[41] Yuehua Z, Thommey PT, Ankur D, Hong Z, Pascale R L, Istvan J. Majoros, James RBJr. Targeted Dendrimeric Anticancer Prodrug: A Methotrexate-Folic Acid-Poly (amidoamine) Conjugate and a Novel, Rapid, “One Pot” Synthetic Approach. Bioconj Chem 2010; 21: 489–495.
[42] David DND, Eberhard N, Margo N, Constance EJ, van R. Carrier-bound Methotrexate. III, Antiproliferative activity of macromolecular MTX conjugates against the human HeLa and colon carcinoma cell lines. S Afr J Chem 2003; 59: 33-42.
[43] Khatri S, Das NG, Das SK. Effect of methotrexate conjugated PAMAM dendrimers on the viability of MES-SA uterine cancer cells. J Pharm Bioall Sci 2014; 6: 297-302.
[44] Linda S L, John J, Weixian M, Verica R, Kishor M W, Helen M B. Methotrexate loaded poly (l-lactic acid) microspheres for intra-articular delivery of methotrexate to the joint. J Pharm Sci, 2004; 93: 943-956.
[45] Hawker CJ, Fre´chet JMJ. Preparation of Polymers with Controlled Molecular Architecture - A New Convergent Approach to Dendritic Macromolecules. J Am Chem Soc 1990; 112: 7638-7647.
[46] Kono K, Liu M, Fre´chet JMJ. Design of Dendritic Macromolecules Containing Folate or Methotrexate Residues. Bioconj Chem 1999; 10: 1115-1121.
[47] Dang JM, Leong KW. Natural polymers for gene delivery and tissue engineering. Adv Drug Deliv Rev 2006; 58: 487–499.
[48] Ratner BD, Bryant SJ. Biomaterials: Where we have been and where we are going. Ann Rev Biomed Eng 2004; 6: 41–75.
[49] Chen J, Jo S, Park K. Polysaccharide hydrogels for protein drug delivery. Carbohydr Polym 1995; 28: 69–76.
[50] Mizrahy S, Peer D. Polysaccharides as building blocks for nanotherapeutics. Chem Soc Rev 2012; 41: 2623–2640.
[51] Liu Z, Jiao Y, Wang Y, Zhou C, Zhang Z. Polysaccharides-based nanoparticles as drug delivery systems. Adv Drug Deliv Rev 2008; 60: 1650–1662.
[52] Saravanakumar G, Jo DG, Park JH. Polysaccharide based nanoparticles: A versatile Platform for Drug Delivery and Biomedical Imaging. Curr Med Chem 2012; 19: 3212–3219.
[53] Mehvar R. Recent trends in the use of polysaccharides for improved delivery of therapeutic agents: pharmacokinetic and pharmacodynamic perspectives. Curr Pharm Biotechnol 2003; 4: 283302.
[54] Dmitry N, Renata B, Urszula K, Monika J, Mohamed SO, Janusz B, Adam O. Antitumor Properties and Toxicity of Dextran-methotrexate Conjugates are Dependent on the Molecular Weight of the Carrier. Anticancer Res 2006; 26: 1135-1144.
[55] Ying C, Frederick E, Tan RL. Synthesis and Characterization of Dextran−Peptide−Methotrexate Conjugates for Tumor Targeting via Mediation by Matrix Metalloproteinase II and Matrix Metalloproteinase IX. Bioconjug Chem 2004; 15: 931-941.
[56] Goszczyński TM, Filip-Psurska B, Kempińska K, Wietrzyk J, Boratyński J. Hydroxyethyl starch as an effective methotrexate carrier in anticancer therapy. Pharmacol Res Perspect 2014; 2: e00047.
[57] Shoshy M, Dalit LM, Dan P; Sweet Fairytale. Carbohydrates as Backbones for Glyconanomedicine. Isr J Chem 2013; 53: 616-629.
[58] Singh UV, Aithal KS, Udupa N. Physicochemical and Biological Studies of Inclusion Complex of Methotrexate with β-Cyclodextrin. Pharma Sci 1997; 3: 573-577.
[59] Juan-Juan Y, Sonali S, Stepan P S, Zhi-Xin W, Zhi-Wei Z. Synthesis and Biological Evaluation of Novel Folic Acid Receptor-Targeted, β-Cyclodextrin-Based Drug Complexes for Cancer Treatment. PLOS One 2013; 8: e62289.
[60] Taheri A, Dinarvand R, Salman NF, Khorramizadeh MR, Taheri BA, Mansoori P, Atyabi F. Use of biotin targeted methotrexate-human serum albumin conjugated nanoparticles to enhance methotrexate antitumor efficacy. Int J Nanomed 2011; 6: 1863-74.
[61] Shin JM, Kim SH, Thambi T, You DG, Jeon J, Lee JO, Chung BY, Jo DG, Park JH. A hyaluronic acid-methotrexate conjugate for targeted therapy of rheumatoid arthritis. Chem Commu 2014; 50: 7632-7635.
[62] Homma A, Sato H, Okamachi A, Emura T, Ishizawa T, Kato T, Matsuura T, Sato S, Tamura T, Higuchi Y. Novel hyaluronic acid–methotrexate conjugates for osteoarthritis treatment. Bioorg Med Chem 2009; 17: 4647–4656.
[63] Anna M, Monica C. Hyaluronic Acid Bioconjugates for the Delivery of Bioactive Molecules. Polym 2014; 6: 346-369.
[64] Budzynska R, Nevozhay D, Kanska U, Jagiello M, Opolski A, Wietrzyk J, BoratynskiJ. Antitumor activity of mannan-methotrexate conjugate in vitro and in vivo. Oncol Res 2007; 16: 415-421.
[65] Blauchfield J, Toth I. Lipid, sugar and polysaccharide based delivery system. Current Med Chem 2004; 11: 2375-2382.
[66] Lockett T, Reilly W, Manthey M, Wells X, Cameron F, Moghddam M, Johnston J, Smith K, Francis C, Yang Q, Whittaker R. Tris Lipidation: A Chemically Flexible Technology For Modifying The Delivery Of Drugs and Genes. Clin Exp Pharmac Physio 2000; 27: 563-567.
[67] Pignatello R, Spampinato G, Sorrenti V, Di GC, Vicari L, McGuire JJ, Russell CA, Puglisi G, Toth I. Lipophilic methotrexate conjugates with antitumor activity. Eur J Pharma Sci 2000; 10: 237-245.
[68] Jaroslav T, Andrew DM, Zuzana K, Róbert L, Josef M, Štěpán K, Milan R. Lipid-Based Nanoparticles and Microbubbles – Multifunctional Lipid-Based Biocompatible Particles for in vivo Imaging and Theranostics. Advances in Bioengineering 2015; edited by Pier Andrea Serra, ISBN 978-953-51-2141-1.
[69] Wang X, Liu P, Yang W, Li L, Li P, Liu Z, Zhuo Z, Gao Y. Microbubbles coupled to methotrexate-loaded liposomes for ultrasound-mediated delivery of methotrexate across the blood–brain barrier. Int J Nanomed 2014; 9: 4899-4909.
[70] Furuhata A, Honda K, Shibata T, Chikazawa M, Kawai Y, Shibata N, Uchida K. Monoclonal antibody against protein- bound glutathione: use of glutathione conjugate of acrolein-modified proteins as an immunogen. Chem Res Toxicol 2012; 25: 1393-1401.
[71] Heidi LP, Pina MC, Shrikant D, Sanjeev G, Gretchen MS, Gregory DV, Robert MB. Antibody-drug conjugates: Current status and future directions. Drug Discov Today 2013; 1-13.
[72] Franco D, Paola B, Luigi Cattel. Immunotoxins and Anticancer Drug Conjugate Assemblies: The Role of the Linkage between Components. Toxins 2011; 3: 848-883.
[73] Martin CG, Robert WB. An improved synthesis of a Methotrexate-Albumin-791T/36 Monoclonal Antibody Conjugate cytotoxic to Human Osteogenic Sarcoma Cell Lines. Cancer Res 1986; 46: 2407-12.
[74] Raymond E, Nicole HPC, Jan W, Liesbeth VD, Peter JB, Piet B. Transport of glutathione prostaglandin A conjugates by the multidrug resistance protein 1. Febs Letters 1997; 419: 112-116.
[75] Noriaki E, Yoshinori K, Yumiko T, Masahiko S, Naoji U, Kazuo K, Takeshi H. In Vitro Cytotoxicity of a Human Serum Albumin-mediated Conjugate of Methotrexate with Anti-MM46 Monoclonal Antibody. Cancer Res 1987; 47: 1076-1080.
[76] Noriaki K, Yumiko T, Naoji U, Kazuo K, Kenzo W, Masahiko S, Yoshinori K, Takeshi H. Nature of Linkage and Mode of Action of Methotrexate Conjugated with Antitumor Antibodies: Implications for Future Preparation of Conjugates. Cancer Res 1988; 48: 3330-3335.
[77] Rowland AJ, Harper ME, Wilson DW, Griffiths K. The effect of an anti-membrane antibody methotrexate conjugate on the human prostatic tumor line PC3. B J Cancer 1990; 61: 702-708.
[78] Geoffrey P, Kenia K. Antibody-Targeted Drugs for the Therapy of Cancer. J Drug Target 1994; 2: 183-215.
[79] Cloe K. Macrocyclic chemistry, current trends and future perspectives. Springer 2005; 407-425.
[80] Wen-Hao W, Mark F, Darren M, Zhong W, Phil L, Mimi M, Dale M, Jonathan LS. Gadolinium texaphyrin–methotrexate conjugates. Towards improved cancer chemotherapeutic agents. Org Biomol Chem 2005; 3: 3290-3296.
[81] Feng L, Liu Z. Graphene in biomedicine: opportunities and challenges. Nanomedicine (Lond) 2011; 6: 317-324.
[82] Georgakilas V, Otyepka M, Bourlinos AB, Chandra V, Kim N. Functionalization of graphenes: Covalent and noncovalent approaches, derivatives and applications. Chem Rev 2012; 112: 6156-6214.
[83] Singh I, Rehni AK, Kumar P, Kumar M, Aboul-Enein HY. Carbon Nanotubes- Synthesis, Properties and Pharmaceutical Applications. Fullerenes, Nanotubes and Carbon Nanostruct 2009; 17: 361–377.
[84] Huiyun W, Yongyong L. Redox Sensitive Nanoparticles with Disulfide Bond Linked Sheddable Shell for Intracellular Drug Delivery. Med Chem 2014; 4: 748-755.
[85] Romberg B, Hennink WE, Storm G. Sheddable coatings for long circulating nanoparticles. Pharm Res 2008; 25: 55-71.
[86] Mohammad JA, Jaleh B, Ali MA, Soodabeh D, Yadollah O, Mohammad-Reza R. Methotrexate-conjugated quantum dots: synthesis, characterisation and cytotoxicity in drug resistant cancer cells. J Drug Targeting 2016; 24: 120-133.
[87] Pei JW, Keng LO, Jem KC, Hsiao PF, Shin HT, Wei XL, Jia YC. Methotrexate-conjugated AgInS2/ZnS quantum dots for optical imaging and drug delivery. Material Letter 2014; 128: 412-416.
[88] Prato M, Kostarelos K, Bianco A. Functionalized carbon nanotubes in drug design and discovery. Acc Chem Res 2008; 41: 60-8.
[89] Pastorin G, Wu W, Wieckowski S, Briand JP, Kostarelos K, Prato M, Bianco A. Double functionalization of carbon nanotubes for multimodal drug delivery. Chem Commun 2006; 11: 1182-4.
[90] Samorı C, Ali-Boucetta H, Sainz R, Guo C, Toma FM, Fabbro C, da Ros T, Prato M, Kostarelos K, Bianco A. Enhanced anticancer activity of multi-walled carbon nanotube-methotrexate conjugates using cleavable linkers. Chem Commun 2010; 46: 1494-6.
[91] Marega R, Bergamin M, Aroulmoji V, Dinon F, Prato M, Murano E. Hyaluronan-carbon nanotube derivatives: Synthesis, conjugation with model drugs, and DOSY NMR characterization. Eur J Org Chem 2011; 2011: 5617–5625.
[92] Xinlin Y, Ali E, Jie L, Quanjun C. Fullerene–biomolecule conjugates and their biomedicinal applications. Int J Nanomed 2014; 9: 77–92.
[93] Xiunan W, Yi L, Jingcheng X, Shengjuan L, Fada Z, Qian Y, Xiao Z. Molecular Dynamics Study of Stability and Diffusion of Graphene-Based Drug Delivery Systems. J Nanomaterials 2015; 1-14.
[94] Jun Yue, Shi Liu, Rui Wang, Xiuli Hu, Zhigang Xie, Yubin Huang, Xiabin Jing. Transferrin-Conjugated Micelles: Enhanced Accumulation and Antitumor Effect for Transferrin-Receptor-Overexpressing Cancer Models. Mol Pharmaceutics 2012; 9: 1919–1931.
[95] Woitoniszak M, Urbas K, Peruzynska M, Kurzawski M, Drozdzik M, Mijowska E. Covalent conjugation of graphene oxide with methotrexate and its antitumor activity. Chem Phys Letter 2013; 151-156.
[96] Abbing A, Blaschke UK, Grein S, Kretschmar M, Stark CMB, Thies MJW, Walter J, Weigand M, Woith DC, Hess J, Reiser COA. Efficient Intracellular Delivery of a Protein and a Low Molecular Weight Substance via Recombinant Polyomavirus-like Particles. J Biol Chem 2004; 279: 27410.
[97] Bert JL, Wen-Lin PT, Foad M, Edward AP, Anne B M, Daniel T K. Inhibition of Transferrin Iron Release Increases in Vitro Drug Carrier Efficacy. J Control Release. 2007; 117: 403–412.
[98] Justin PS, Margaret AP, Nicholas AP. Cellular Revaluation of Synthesized Insulin/ Transferrin Bioconjugates for Oral Insulin Delivery Using Intelligent Complexation. Macromol Biosci 2010; 10: 299–306.
[99] Ren I K, Dusad I A, Dong R, Quan L. Albumin as a Delivery Carrier for Rheumatoid Arthritis. J Nanomed Nanotechol 2013; 4: 4.
[100] Wunder A, Müller-Ladner U, Stelzer EHK, Funk J, Neumann E, Stehle G, Pap T, Sinn H, Gay S, Fiehn Ch. Albumin-Based Drug Delivery as Novel Therapeutic Approach for Rheumatoid Arthritis. J Immunology 2003; 170: 4793-4801.
[101] Jin-Ho Choy et al. Layered double hydroxide as an efficient drug reservoir for folate derivatives. Biomaterials 2004; 25: 3059–3064.
[102] Jae-Min Oh et al. Efficient delivery of anticancer drug MTX through MTX-LDH Nanohybridsystem. J Phys & Chem Solids 2006; 67: 1024–1027.
[103] Chakraborty M, Dasgupta S, Saundrapandian C, Basu D. Methotrexate intercalated ZnAl-layered double hydroxide. J Solid State Chem 2011; 184: 2439-2445.
[104] Shams A. Nadhum, Mohammed HM. Design, Synthesis, Characterization and Preliminary Anticancer Study for Methotrexate Silibinin Conjugates. Iraqi J Pharm Sci 2015; 24: 74-84.
[105] DeBin JA, Strichartz GR. Chloride channel inhibition by the venom of the scorpion Leiurus quinquestriatus. Toxicon 1991; 29: 1403–8.
[106] Conroy S, Chen F, Zachary S, Omid V, Stacey H, Donghoon L, Richard GE, Jim O, Miqin Z. Tumor-targeted drug delivery and MRI contrast enhancement by chlorotoxin-conjugated iron oxide nanoparticles. Nanomedicine 2008; 3: 495–505.
[107] Gauri S, Anjani KT, Nitin K, Deepa S, Pushpa M, Harish C, Anil K M. Cancer Biotherapy and Radiopharmaceuticals. 2008; 23: 571-580.
[108] Kuznetsova N, Kandyba A, Vostrov I, Kadykov V, Gaenko G, Molotkovsky J, Vodovozova E. Liposomes loaded with lipophilic prodrugs of methotrexate and melphalan as convenient drug delivery vehicles. J Drug Del Sci Tech 2009; 19: 51-59.
[109] Stephan JK, Robert FS, John CDD, James CH. Chemically induced dimerization of dihydrofolate reductase by a homobifunctional dimer of methotrexate. Chem & Bio 2000; 7: 313-321.
[110] Carston RW. Protein nanorings. US8236925 B1 Aug 7, 2012.
[111] Fazle H, Richard PS, Helen MC, Georges LS. Targeted Delivery of Antineoplastic Agent to Bone: Biodistribution Studies of Technetium-99m-Labeled Gem-Bisphosphonate Conjugate of Methotrexate. J Nuclear Med 1996; 37: 105-107.
[112] Xiao-Hong O, An-Ren K, Zheng-Lu L, Xian P. Receptor binding characteristics and cytotoxicity of insulin-methotrexate. World J Gastroenterol 2004; 10: 2430–2433.
[113] Hugh MT. Compounds and methods for treating cancer. US8501906 B2, Aug 6, 2013.
[114] Samra ZQ, Ahmad S, Javeid M, Dar N, Aslam MS, Gull I, Ahmad MM. Anticancer medicines (Doxorubicin and methotrexate) conjugated with magnetic nanoparticles for targeting drug delivery through iron. Prep Biochem Biotechnol 2013; 43: 781-97.
[115] Ashwanikumar N, Kumar NA, Nair AS, Kumar GSV. Dual drug delivery of 5-fluorouracil (5-FU) and methotrexate (MTX) through random copolymeric nanomicelles of PLGA and polyethylenimine demonstrating enhanced cell uptake and cytotoxicity. Colloids Surf B Biointerfaces 2014; 23: 520-8.
[116] Virginia WC. Covalent chemical inducers of protein dimerization and their uses in high throughput binding screens. WO 2002059272 A2, Aug 1, 2002.
[117] Virginia WC. Binding and catalysis screen for high throughput determination of protein function using chemical inducers of dimerization. US 20020168737 A1, Nov 14, 2002.
[118] Virginia WC. Methods and assays for screening protein targets. US 7419780 B2, Sep 2, 2008.
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