Synthesis and in vitro evaluation of methotrexate conjugated O,N-carboxymethyl chitosan via peptidyl spacers
Source abstract
Abstract
The use of methotrexate (MTX), an anticancer drug for the treatment of hematologic malignancies, has been limited in the clinical application due to its poor water solubility, high clearance rate, and lack of target specificity. To solve these problems, O,N-carboxymethyl chitosan–dipeptide-MTX conjugates have been synthesized and characterized by fourier transform infrared radiation spectroscopy and proton nuclear magnetic resonance (1H NMR). All polymeric conjugates showed satisfactory water solubility. The results of the study revealed that drug release and toxicity were affected by employing polymeric conjugation strategy and dipeptide spacers [glycylglycine (Gly–Gly), glycyl–l-phenylalanine (Gly–Phe), glycyl–l-tyrosine (Gly–Tyr)]. It has been found that drugs could be effectively loaded and released when polymeric prodrugs were combined with a dipeptide spacer. In conclusion, O,N-CMCS–dipeptide-MTX polymeric prodrugs could potentially be used as responsive drug delivery systems.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Advanced Drug Delivery Systems · RNA Interference and Gene Delivery · Biopolymer Synthesis and Applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (35)
Show source-provided references
1. Alexa IF, Pastravanu CG, Ignat M, Popovici E (2013) A comparative study on long-term MTX controlled release from intercalated nanocomposites for nanomedicine applications. Colloids Surf B 106:135–13910.1016/j.colsurfb.2013.01.022 ↗
2. Anitha A, Maya S, Deepa N, Chennazhi KP, Nair SV, Tamura H, Jayakumar R (2011) Efficient water soluble O-carboxymethyl chitosan nanocarrier for the delivery of curcumin to cancer cells. Carbohydr Polym 83:452–46110.1016/j.carbpol.2010.08.008 ↗
3. Berdowska I (2004) Cysteine proteases as disease markers. Clin Chim Acta 342:41–6910.1016/j.cccn.2003.12.016 ↗
4. Boratyński J, Opolski A, Wietrzyk J, Górski A, Radzikowski C (2000) Cytotoxic and antitumor effect of fibrinogen–methotrexate conjugate. Cancer Lett 148:189–19510.1016/S0304-3835(99)00334-1 ↗
5. Byamba D, Kim D, Kim DS, Jee H, Kim T, Lee S, Kim SM, Baek J, Lee M (2013) Therapeutic effect of cell permeable peptide-conjugated methotrexate on a mouse model of psoriasis induced by imiquimod. J Dermatol Sci 69:e7–e810.1016/j.jdermsci.2012.11.319 ↗
6. Castex C, Lalanne C, Mouchet P, Lemaire M, Lahana R (2005) Regioselective synthesis of peptidic derivatives and glycolamidic esters of Methotrexate. Tetrahedron 61:803–81210.1016/j.tet.2004.11.049 ↗
7. Devanathan G (2003) The design of the substrates for Cathepsin X. Concordia University
8. Devanathan G, Turnbull JL, Ziomek E, Purisima EO, Ménard R, Sulea T (2005) Carboxy-monopeptidase substrate specificity of human cathepsin X. Biochem Biophys Res Commun 329:445–45210.1016/j.bbrc.2005.01.150 ↗
9. Duncan R (1991) Macromolecular prodrugs for use in targeted cancer chemotherapy: melphalan covalently coupled to N-(2-hydroxypropyl) methacrylamide copolymers. J Control Release 16:121–13610.1016/0168-3659(91)90036-D ↗
10. Huennekens FM (1997) Development of methotrexate α-peptides as prodrugs for activation by enzyme-monoclonal antibody conjugates. Adv Enzyme Regul 37:77–9210.1016/S0065-2571(96)00011-8 ↗
11. Lecaille F, Kaleta J, Brömme D (2002) Human and parasitic papain-like cysteine proteases: their role in physiology and pathology and recent developments in inhibitor design. Chem Rev 102:4459–448810.1021/cr0101656 ↗
12. Li M, Choi SK, Thomas TP, Desai A, Lee K, Kotlyar A, Banaszak Holl MM, Baker JR (2012) Dendrimer-based multivalent methotrexates as dual acting nanoconjugates for cancer cell targeting. Eur J Med Chem 47:560–57210.1016/j.ejmech.2011.11.027 ↗
13. Li M, Neoh K, Wang R, Zong B, Tan JY, Kang E (2013) Methotrexate-conjugated and hyperbranched polyglycerol-grafted Fe3O4 magnetic nanoparticles for targeted anticancer effects. Eur J Pharm Sci 48:111–12010.1016/j.ejps.2012.10.008 ↗
14. Mao Z, Ma L, Zhou J, Gao C, Shen J (2005) Bioactive thin film of acidic fibroblast growth factor fabricated by layer-by-layer assembly. Bioconjug Chem 16:1316–132210.1021/bc049755b ↗
15. Meško Brguljan VP, Igor Križaj TP (2003) Human brain cathepsin H as a neuropeptide and bradykinin metabolizing enzyme. Peptides 24:1977–198410.1016/j.peptides.2003.09.018 ↗
16. Mort JS, Buttle DJ (1997) Cathepsin B. Int J Biochem Cell B 29:715–72010.1016/S1357-2725(96)00152-5 ↗
17. Nägler DK, Ménard R (1998) Human cathepsin X: a novel cysteine protease of the papain family with a very short proregion and unique insertions. FEBS Lett 434:135–13910.1016/S0014-5793(98)00964-8 ↗
18. Nägler DK, Lechner AM, Oettl A, Kozaczynska K, Scheuber H, Gippner-Steppert C, Bogner V, Biberthaler P, Jochum M (2006) An enzyme-linked immunosorbent assay for human cathepsin X, a potential new inflammatory marker. J Immunol Methods 308:241–25010.1016/j.jim.2005.11.002 ↗
19. Narayani R, Panduranga Rao K (1996) Biodegradable microspheres using two different gelatin drug conjugates for the controlled delivery of methotrexate. Int J Pharm 128:261–26810.1016/0378-5173(95)04323-3 ↗
20. Nogueira DR, Tavano L, Mitjans M, Pérez L, Infante MR, Vinardell MP (2013) In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles. Biomaterials 34:2758–277210.1016/j.biomaterials.2013.01.005 ↗
21. Obermajer N, Doljak B, Jamnik P, Fonović UP, Kos J (2009) Cathepsin X cleaves the C-terminal dipeptide of alpha- and gamma-enolase and impairs survival and neuritogenesis of neuronal cells. Int J Biochem Cell B 41:1685–169610.1016/j.biocel.2009.02.019 ↗
22. Ofner CM III, Pica K, Bowman BJ, Chen C (2006) Growth inhibition, drug load, and degradation studies of gelatin/methotrexate conjugates. Int J Pharm 308:90–9910.1016/j.ijpharm.2005.10.037 ↗
23. Paulick MG, Bogyo M (2011) Development of activity-based probes for Cathepsin X. ACS Chem Biol 6:563–57210.1021/cb100392r ↗
24. Pignatello R, Spampinato G, Sorrenti V, Di Giacomo C, Vicari L, McGuire JJ, Russell CA, Puglisi G, Toth I (2000) Lipophilic methotrexate conjugates with antitumor activity. Eur J Pharm Sci 10:237–24510.1016/S0928-0987(00)00062-2 ↗
25. Pinguet F, Joulia JM, Martel P, Grosse PY, Astre C, Bressolle F (1996) High-performance liquid chromatographic assay for melphalan in human plasma Application to pharmacokinetic studies. J Chromatogr B 686:43–4910.1016/S0378-4347(96)00184-3 ↗
26. Smal MA, Dong Z, Cheung H, Asano Y, Escoffier L, Costello M, Tattersall MH (1995) Activation and cytotoxicity of 2-α-aminoacyl prodrugs of methotrexate. Biochem Pharmacol 49:567–57410.1016/0006-2952(94)00456-V ↗
27. Šubr V, Strohalm J, Hirano T, Ito Y, Ulbrich K (1997) Poly[N-(2-hydroxypropyl)methacrylamide] conjugates of methotrexate: synthesis and in vitro drug release. J Control Release 49:123–13210.1016/S0168-3659(97)00063-1 ↗
28. Upadhyaya L et al (2013) Biomedical applications of carboxymethyl chitosans. Carbohydr Polym 91(1):452–46610.1016/j.carbpol.2012.07.076 ↗
29. Vila A, Sánchez A, Évora C, Soriano I, McCallion O, Alonso MJ (2005) PLA–PEG particles as nasal protein carriers: the influence of the particle size. Int J Pharm 292:43–5210.1016/j.ijpharm.2004.09.002 ↗
30. Wang Y, Yang X, Yang J, Wang Y, Chen R, Wu J, Liu Y, Zhang N (2011) Self-assembled nanoparticles of methotrexate conjugated O-carboxymethyl chitosan: preparation, characterization and drug release behavior in vitro. Carbohydr Polym 86:1665–167010.1016/j.carbpol.2011.06.080 ↗
31. Wu Z, Shah A, Patel N, Yuan X (2010) Development of methotrexate proline prodrug to overcome resistance by MDA-MB-231 cells. Bioorg Med Chem Lett 20:5108–511210.1016/j.bmcl.2010.07.024 ↗
32. Xu Y, Zhan C, Fan L, Wang L, Zheng H (2007) Preparation of dual crosslinked alginate–chitosan blend gel beads and in vitro controlled release in oral site-specific drug delivery system. Int J Pharm 336:329–33710.1016/j.ijpharm.2006.12.019 ↗
33. Yang Y, Aloysius H, Inoyama D, Chen Y, Hu L (2011) Enzyme-mediated hydrolytic activation of prodrugs. Acta Pharm Sin B 1:143–15910.1016/j.apsb.2011.08.001 ↗
34. Zheng H, Zhang X, Yin Y, Xiong F, Gong X, Zhu Z, Lu B, Xu P (2011a) In vitro characterization, and in vivo studies of crosslinked lactosaminated carboxymethyl chitosan nanoparticles. Carbohydr Polym 84:1048–105310.1016/j.carbpol.2010.12.067 ↗
35. Zheng H, Rao Y, Yin Y, Xiong X, Xu P, Lu B (2011b) Preparation, characterization, and in vitro drug release behavior of 6-mercaptopurine-carboxymethyl chitosan. Carbohydr Polym 83:1952–195810.1016/j.carbpol.2010.10.069 ↗