Folic acid-modified methotrexate-conjugated PEGylated poly(ε-caprolactone) nanoparticles for targeted delivery
Source abstract
Abstract
Functionalized nanoparticles of polymer–drug conjugates of PEGylated poly(e-caprolactone) (PEGylated P(CL)) with methotrexate (MTX) and folic acid (FOL) were developed and investigated for their targeting efficiency. FOL- and MTX-conjugated PEGylated P(CL) copolymers were employed to prepare P(MTXCLCL)2–PEG NPs and FOL–P(MTXCLCL)2–PEG NPs. By varying the amount of MTX, the different characteristics of nanoparticles were obtained. The results showed that an increase in particle size and more negative surface charge of P(MTXCLCL)2–PEG NPs were related to an increased amount of MTX along the polymer backbone. After being decorated with FOL, the particle size increased by nearly twofolds while the zeta potential decreased. All nanoparticles were spherical as observed under SEM micrographs. The release profiles showed pH-dependent and sustained release over 20 days. Higher extent of MTX was released in pH 4.5 medium as compared to the drug release in pH 7.4 medium. All nanoparticles showed greater toxicity to MCF-7 cells than A549 cells. In addition, FOL–P(MTXCLCL)2–PEG NPs exhibited the highest toxicity to MCF-7 cells as compared to all P(MTXCLCL)2–PEG NPs and free MTX. Furthermore, FOL–P(MTXCLCL)2–PEG NPs were internalized into MCF-7 cells higher than P(MTXCLCL)2–PEG NPs and FOL–P(MTXCLCL)2–PEG NPs incubated with free FOL. The results indicated that FOL–P(MTXCLCL)2–PEG NPs efficiently entered into MCF-7 cells via folate receptor-mediated endocytosis together with adsorptive endocytosis.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Nanoparticle-Based Drug Delivery · Graphene and Nanomaterials Applications · Polymer Surface Interaction Studies
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (60)
Show source-provided references
1. Albanese A, Tang PS, Chan WC (2012) The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng 14:1–1610.1146/annurev-bioeng-071811-150124 ↗
2. Avgoustakis K (2004) Pegylated poly(lactide) and poly(lactide-co-glycolide) nanoparticles: preparation, properties and possible applications in drug delivery. Curr Drug Deliv 1:321–33310.2174/1567201043334605 ↗
3. Bilati U, Allémann E, Doelker E (2005) Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles. Eur J Pharm Sci 24:67–7510.1016/j.ejps.2004.09.011 ↗
4. Campbell IG, Jones TA, Foulkes WD, Trowsdale J (1991) Folate-binding protein is a marker for ovarian cancer. Cancer Res 51:5329–5338
5. Cheow WS, Hadinoto K (2011) Enhancing encapsulation efficiency of highly water soluble antibiotic in poly(lactic-co-glycolic acid) nanoparticles: modifications of standard nanoparticle preparation methods. Colloids Surf A Physicochem Eng Asp 370:79–8610.1016/j.colsurfa.2010.08.050 ↗
6. Cho BK, Roy EJ, Patrick TA, Kranz DM (1997) Single-chain Fv/folate conjugates mediate efficient lysis of folate receptor-positive tumor cells. Bioconjug Chem 8:338–34610.1021/bc9700244 ↗
7. Dang W, Colvin OM, Brem H, Saltzman WM (1994) Covalent coupling of methotrexate to dextran enhances the penetration of cytotoxicity into a tissue-like matrix. Cancer Res 54:1729–1735
8. Desai MP, Labhasetwar V, Walter E et al (1997) The mechanism of uptake of biodegradable microparticles in Caco-2 cells is size dependent. Pharm Res 14:1568–157310.1023/A:1012126301290 ↗
9. Eldar-Boock A, Miller K, Sanchis J et al (2011) Integrin-assisted drug delivery of nano-scaled polymer therapeutics bearing paclitaxel. Biomaterials 32:3862–387410.1016/j.biomaterials.2011.01.073 ↗
10. Errico C, Bartoli C, Chiellini F, Chiellini E (2009) Poly(hydroxyalkanoates)-based polymeric nanoparticles for drug delivery. J Biomed Biotechnol. doi: 10.1155/2009/571702
11. Gong CY, Shi S, Dong PW et al (2009) Synthesis and characterization of PEG–PCL–PEG thermosensitive hydrogel. Int J Pharm 365:89–9910.1016/j.ijpharm.2008.08.027 ↗
12. Gref R, Lück M, Quellec P et al (2000) ‘Stealth’ corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf B 18:301–31310.1016/S0927-7765(99)00156-3 ↗
13. Greish K (2007) Enhanced permeability and retention of macromolecular drugs in solid tumor: a royal gate for targeted anticancer nanomedicines. J Drug Target 15:457–46410.1080/10611860701539584 ↗
14. He C, Hu Y, Yin L et al (2010) Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials 31:3657–366610.1016/j.biomaterials.2010.01.065 ↗
15. Hilgenbrink AR, Low PS (2005) Folate receptor-mediated drug targeting: from therapeutics to diagnostics. J Pharm Sci 94:2135–214610.1002/jps.20457 ↗
16. Hu Y, Xie J, Tong YW, Wang CH (2007) Effect of PEG conformation and particle size on the cellular uptake efficiency of nanoparticles with the HepG2 cells. J Control Release 118:7–1710.1016/j.jconrel.2006.11.028 ↗
17. Issarachot O, Suksiriworapong J, Sripha K, Junyaprasert VB (2012) Modification of tricomponent and dicomponent poly(ε-caprolactone)-co-poly(ethylene glycol) with methotrexate and folic acid. J Appl Polym Sci. doi: 10.1002/app.38781
18. Khandare J, Minko T (2006) Polymer-drug conjugates: progress in polymeric prodrugs. Prog Polym Sci 31:359–39710.1016/j.progpolymsci.2005.09.004 ↗
19. Kim SH (2005) Target-specific cellular uptake of PLGA nanoparticles coated with poly(l-lysine)-poly(ethylene glycol)-folate conjugate. Langmuir 21:8852–885710.1021/la0502084 ↗
20. Kim CK, Hwang SA (1993) Pharmacokinetics and organ distribution of 3H-methotrexate and 3H-methotrexate–human serum albumin conjugates in mice. Drug Dev Ind Pharm 19:961–97010.3109/03639049309062994 ↗
21. Kim MS, Hyun H, Seo KS et al (2006) Preparation and characterization of MPEG–PCL diblock copolymers with thermo-responsive sol–gel–sol phase transition. J Polym Sci Part A 44:5413–542310.1002/pola.21659 ↗
22. Koo OM, Rubinstein I, Onyuksel H (2005) Role of nanotechnology in targeted drug delivery and imaging: a concise review. Nanomedicine 1:193–21210.1016/j.nano.2005.06.004 ↗
23. Kranz DM, Patrick TA, Brigle KE et al (1995) Conjugates of folate and anti-T-cell-receptor antibodies specifically target folate-receptor-positives tumor cells for lysis. Proc Natl Acad Sci USA 92:9057–906110.1073/pnas.92.20.9057 ↗
24. Kulthe SS, Inamdar NN, Choudhari YM et al (2011) Mixed micelle formation with hydrophobic and hydrophilic Pluronic block copolymers: implications for controlled and targeted drug delivery. Colloids Surf B Biointerfaces 88:691–69610.1016/j.colsurfb.2011.08.002 ↗
25. Lah TT, Cercek M, Blejec A et al (2000) Cathepsin B, a prognostic indicator in lymph node-negative breast carcinoma patients: comparison with cathepsin D, cathepsin L, and other clinical indicators. Clin Cancer Res 6:578–584
26. Lee RS, Huang YT (2010) Synthesis and characterization of amphiphilic triblock-graft PEG-(b-PαN3CL-g-Alkyne)2 degradable copolymers. J Polym Res 17:697–70610.1007/s10965-009-9358-8 ↗
27. Li MH, Choi SK, Thomas TP et al (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 ↗
28. Liu SQ, Wiradharma N, Gao SJ et al (2007) Bio-functional micelles self-assembled from a folate-conjugated block copolymer for targeted intracellular delivery of anticancer drugs. Biomaterials 28:1423–143310.1016/j.biomaterials.2006.11.013 ↗
29. Maeda H, Bharate GY, Daruwalla J (2009) Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect. Eur J Pharm Biopharm 71:409–41910.1016/j.ejpb.2008.11.010 ↗
30. McCarthy JR, Weissleder R (2008) Multifunctional magnetic nanoparticles for targeted imaging and therapy. Adv Drug Deliv Rev 60:1241–125110.1016/j.addr.2008.03.014 ↗
31. Mi Y, Liu Y, Feng SS (2011) Formulation of docetaxel by folic acid-conjugated d-α-tocopheryl polyethylene glycol succinate 2000 (Vitamin E TPGS2k) micelles for targeted and synergistic chemotherapy. Biomaterials 32:4058–406610.1016/j.biomaterials.2011.02.022 ↗
32. Mo G, Hua X, Liu S et al (2012) Influence of coupling bonds on the anti-tumor activity of polymer–pirarubicin conjugates. Eur J Pharm Sci 46:329–33510.1016/j.ejps.2012.02.013 ↗
33. Moghimi SM, Hunter AC, Murray JC (2001) Long-circulating and target-specific nanoparticles: theory and practice. Pharmacol Rev 53:283–31810.1016/S0031-6997(24)01494-7 ↗
34. Moon C, Kwon YM, Lee WK et al (2007) In vitro assessment of a novel polyrotaxane-based drug delivery system integrated with a cell-penetrating peptide. J Control Release 124:43–5010.1016/j.jconrel.2007.08.029 ↗
35. Otsuka H, Nagasaki Y, Kataoka K (2003) PEGylated nanoparticles for biological and pharmaceutical applications. Adv Drug Deliv Rev 55:403–41910.1016/S0169-409X(02)00226-0 ↗
36. Pan J, Feng SS (2008) Targeted delivery of paclitaxel using folate-decorated poly(lactide)-vitamin E TPGS nanoparticles. Biomaterials 29:2663–267210.1016/j.biomaterials.2008.02.020 ↗
37. Patanasethanont D, Nagai J, Matsuura C et al (2007) Modulation of function of multidrug resistance associated-proteins by Kaempferia parviflora extracts and their components. Eur J Pharmacol 566:67–7410.1016/j.ejphar.2007.04.001 ↗
38. Peracchia MT, Gref R, Minamitake Y et al (1997) PEG-coated nanospheres from amphiphilic diblock and multiblock copolymers: investigation of their drug encapsulation and release characteristics. J Control Release 46:223–23110.1016/S0168-3659(96)01597-0 ↗
39. Piao L, Dai Z, Deng M et al (2003) Synthesis and characterization of PCL/PEG/PCL triblock copolymers by using calcium catalyst. Polymer 44:2025–203110.1016/S0032-3861(03)00087-9 ↗
40. Rejman J, Oberle V, Zuhorn IS, Hoekstra D (2004) Size-dependent internalization of particle via the pathways of clathrin and caveolae-mediated endocytosis. Biochem J 377:159–16910.1042/bj20031253 ↗
41. Ren F, Chen RD, Wang Y et al (2011) Paclitaxel-loaded poly(butylcyanoacrylate) nanoparticle delivery system to overcome multidrug resistance in ovarian cancer. Pharm Res 28:897–90610.1007/s11095-010-0346-9 ↗
42. Shen Z, Wei W, Zhao Y et al (2008) Thermosensitive polymer-conjugated albumin nanospheres as thermal targeting anti-cancer drug carrier. Eur J Pham Sci 35:271–28210.1016/j.ejps.2008.07.006 ↗
43. Singh P, Gupta U, Asthana A, Jain NK (2008) Folate and folate–PEG–PAMAM dendrimers: synthesis, characterization, and targeted anticancer drug delivery potential in tumor bearing mice. Bioconjug Chem 19:2239–225210.1021/bc800125u ↗
44. Soares de Oliveira J, Pereira Bezerra D, Teixeira de Freitas CD et al (2007) In vitro cytotoxicity against different human cancer cell lines of laticifer proteins of Calotropis procera (Ait.) R.Br. Toxicol In Vitro 21:1563–157310.1016/j.tiv.2007.05.007 ↗
45. Šubr V, Strohalm J, Hirano T et al (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 ↗
46. Suksiriworapong J, Sripha K, Kreuter J, Junyaprasert VB (2012) Functionalized (poly(ε-caprolactone))2-poly(ethylene glycol) nanoparticles with grafting nicotinic acid as drug carriers. Int J Pharm 423:562–57010.1016/j.ijpharm.2011.11.033 ↗
47. Takakura Y, Hashida M (1996) Macromolecular carrier systems for targeted drug delivery: pharmacokinetic considerations on biodistribution. Pharm Res 13:820–83110.1023/A:1016084508097 ↗
48. Takano M, Otani Y, Tanda M et al (2009) Paclitaxel-resistance conferred by altered expression of efflux and influx transporters for paclitaxel in the human hepatoma cell line, HepG2. Drug Metab Pharmacokinet 24:418–42710.2133/dmpk.24.418 ↗
49. Thomas TP, Majoros IJ, Kotlyar A et al (2005) Targeting and inhibition of cell growth by an engineered dendritic nanodevice. J Med Chem 48:3729–373510.1021/jm040187v ↗
50. Torchilin VP (2001) Structure and design of polymeric surfactant-based drug delivery systems. J Control Release 73:137–17210.1016/S0168-3659(01)00299-1 ↗
51. Ulbrich K, Šubr V (2004) Polymeric anticancer drugs with pH-controlled activation. Adv Drug Deliv Rev 56:1023–105010.1016/j.addr.2003.10.040 ↗
52. Ulbrich K, Michaelis M, Rothweiler F et al (2011) Interaction of folate-conjugated human serum albumin (HSA) nanoparticles with tumour cells. Int J Pharm 406:128–13410.1016/j.ijpharm.2010.12.023 ↗
53. United States Food and Drug Administration (1997) Guidance for industry: dissolution testing of immediate release solid oral dosage forms. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). http://www.fda.gov/cder/guidance/1713bp1.pdf . Accessed 23 Oct 2012
54. Wang Y, Yang X, Yang J et al (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 ↗
55. Weitman SD, Weinberg AG, Coney LR et al (1992) Cellular localization of the folate receptor: potential role in drug toxicity and folate homeostasis. Cancer Res 52:6708–6711
56. Yang X, Deng W, Fu L et al (2008) Folate-functionalized polymeric micelles for tumor targeted delivery of a potent multidrug-resistance modulator FG020326. J Biomed Mater Res Part A 86:48–6010.1002/jbm.a.31537 ↗
57. Yoo HS, Park TG (2004) Folate-receptor-targeted delivery of doxorubicin nano-aggregates stabilized by doxorubicin–PEG–folate conjugate. J Control Release 100:247–25610.1016/j.jconrel.2004.08.017 ↗
58. Zhang Y, Zhuo RX (2005) Synthesis and in vitro drug release behavior of amphiphilic triblock copolymer nanoparticles based on poly (ethylene glycol) and polycaprolactone. Biomaterials 26:6736–674210.1016/j.biomaterials.2005.03.045 ↗
59. Zhang C, Zhao LQ, Dong YF et al (2010) Folate-mediated poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) nanoparticles for targeting drug delivery. Eur J Pharm Biopharm 76:10–1610.1016/j.ejpb.2010.05.005 ↗
60. Zhao P, Wang H, Yu M et al (2010) Paclitaxel-loaded, folic-acid-targeted and TAT-peptide-conjugated polymeric liposomes: in vitro and in vivo evaluation. Pharm Res 27:1914–192610.1007/s11095-010-0196-5 ↗