Polímeros: Ciência e Tecnologia
Polímeros: Ciência e Tecnologia
Scientific & Technical Article

Influence of PLGA and PLGA-PEG on the dissolution profile of oxaliplatin

Pereira, Emiliane Daher; Cerruti, Renata; Fernandes, Edson; Peña, Luis; Saez, Vivian; Pinto, José Carlos; Ramón, José Angel; Oliveira, Geiza Esperandio; Souza Júnior, Fernando Gomes de

Downloads: 0
Views: 424


Oxaliplatin was inserted into polymeric matrices aiming to study the interaction of this drug with these polymers and its capability to diffuse to the environment. Tested polymers were: (1) polyethylene glycol (PEG), (2) poly(lactic-co-glycolic acid) (PLGA), and (3) a copolymer of them (PLGA-PEG). The latter two were synthesized by us using polycondensation in bulk. Oxaliplatin was included in the matrices by the melt mixing process followed by casting. Fourier tran sform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H-NMR) and X-ray diffraction (DRX) studies of the polymers were performed proving the obtaining of the desired materials. In addition, the interaction between drug and matrices and the release profile of the oxaliplatin from these matrices were analyzed. Among them, PEG did not control the oxaliplatin release. In turn, PLGA and PLGA-PEG present drug release profiles quite similar. Oxaliplatin was completely released from PLGA and PLGA-PEG in 5 hours, by a relaxation mechanism. There was no evidence of oxaliplatin interaction with the different polymers. In addition, as the PEG improves the biocompatibility and biomasking, obtained results prove the obtaining of a drug release system, which allowed the total use of the drug improving the cancer treatment and even the welfare of the patients.


oxaliplatin, drug delivery, biodegradable polymer, PLGA-PEG, block copolymer


1. Parveen, S., & Sahoo, S. (2011). Long circulating chitosan/PEG blended PLGA nanoparticle for tumor drug delivery. European Journal of Pharmacology, 670(2-3), 372-383. http://dx.doi.org/10.1016/j.ejphar.2011.09.023. PMid:21951969.

2. Pou, S. A., Osella, A. R., Eynard, A. R., Niclis, C., & del Pilar Diaz, M. (2009). Colorectal cancer mortality trends in Córdoba, Argentina. Cancer Epidemiology, 33(6), 406-412. http://dx.doi.org/10.1016/j.canep.2009.09.009. PMid:19896430.

3. Nielsen, D., Palshof, J., Larsen, F., Jensen, B., & Pfeiffer, P. (2014). A systematic review of salvage therapy to patients with metastatic colorectal cancer previously treated with fluorouracil, oxaliplatin and irinotecan +/− targeted therapy. Cancer Treatment Reviews, 40(6), 701-715. http://dx.doi.org/10.1016/j.ctrv.2014.02.006. PMid:24731471.

4. Baena, R., & Salinas, P. (2015). Diet and colorectal cancer. Maturitas, 80(3), 258-264. http://dx.doi.org/10.1016/j.maturitas.2014.12.017. PMid:25619144.

5. Tong, L., Ahn, C., Symanski, E., Lai, D., & Du, X. L. (2014). Temporal trends in the leading causes of death among a large national cohort of patients with colorectal cancer from 1975 to 2009 in the United States. Annals of Epidemiology, 24(6), 411-417. http://dx.doi.org/10.1016/j.annepidem.2014.01.005. PMid:24529646.

6. Wong, C. K., Chen, J., Yu, C. L., Sham, M., & Lam, C. L. (2015). Systematic review recommends the European Organization for Research and Treatment of Cancer colorectal cancer–specific module for measuring quality of life in colorectal cancer patients. Journal of Clinical Epidemiology, 68(3), 266-278. http://dx.doi.org/10.1016/j.jclinepi.2014.09.021. PMid:25455838.

7. Johnstone, T. C. (2014). The crystal structure of oxaliplatin: a case of overlooked pseudo symmetry. Polyhedron, 67, 429-435. http://dx.doi.org/10.1016/j.poly.2013.10.003. PMid:24415827.

8. Zhou, Y., Wan, G., Spizzo, R., Ivan, C., Mathur, R., Hu, X., Ye, X., Lu, J., Fan, F., Xia, L., Calin, G. A., Ellis, L. M., & Lu, X. (2014). miR-203 induces oxaliplatin resistance in colorectal cancer cells by negatively regulating ATM kinase. Molecular Oncology, 8(1), 83-92. http://dx.doi.org/10.1016/j.molonc.2013.09.004. PMid:24145123.

9. Wang, X. J., Li, Y., Luo, L., Wang, H., Chi, Z., Xin, A., Li, X., Wu, J., & Tang, X. (2014). Oxaliplatin activates the Keap1/Nrf2 antioxidant system conferring protection against the cytotoxicity of anticancer drugs. Free Radical Biology & Medicine, 70, 68-77. http://dx.doi.org/10.1016/j.freeradbiomed.2014.02.010. PMid:24556415.

10. Hu, C. J., Wang, B., Tang, B., Chen, B. J., Xiao, Y. F., Qin, Y., Yong, X., Luo, G., Zhang, J. W., Zhang, D., Li, S., He, F., & Yang, S. M. (2015). The FOXM1-induced resistance to oxaliplatin is partially mediated by its novel target gene Mcl-1 in gastric cancer cells. Biochimica et Biophysica Acta, 1849(3), 290-299. http://dx.doi.org/10.1016/j.bbagrm.2014.11.008. PMid:25482013.

11. Janes, K., Wahlman, C., Little, J. W., Doyle, T., Tosh, D. K., Jacobson, K. A., & Salvemini, D. (2015). Spinal neuroimmune activation is independent of T-cell infiltration and attenuated by A3 adenosine receptor agonists in a model of oxaliplatin-induced peripheral neuropathy. Brain, Behavior, and Immunity, 44, 91-99. http://dx.doi.org/10.1016/j.bbi.2014.08.010. PMid:25220279.

12. Mehta, A. M., Van den Hoven, J. M., Rosing, H., Hillebrand, M. J., Nuijen, B., Huitema, A. D., Beijnen, J. H., & Verwaal, V. J. (2015). Stability of oxaliplatin in chloride-containing carrier solutions used in hyperthermic intraperitoneal chemotherapy. International Journal of Pharmaceutics, 479(1), 23-27. http://dx.doi.org/10.1016/j.ijpharm.2014.12.025. PMid:25535649.

13. Zedan, A. H., Hansen, T. F., Fex Svenningsen, A., & Vilholm, O. J. (2014). Oxaliplatin-induced neuropathy in colorectal cancer: many questions with few answers. Clinical Colorectal Cancer, 13(2), 73-80. http://dx.doi.org/10.1016/j.clcc.2013.11.004. PMid:24365057.

14. Kanbara, T., Nakamura, A., Shibasaki, M., Mori, T., Suzuki, T., Sakaguchi, G., & Kanemasa, T. (2014). Morphine and oxycodone, but not fentanyl, exhibit antinociceptive effects mediated by G-protein inwardly rectifying potassium (GIRK) channels in an oxaliplatin-induced neuropathy rat model. Neuroscience Letters, 280, 119-124. http://dx.doi.org/10.1016/j.neulet.2014.08.005. PMid:25128218.

15. Lu, Y., & Chen, S. C. (2004). Micro and nano-fabrication of biodegradable polymers for drug delivery. Advanced Drug Delivery Reviews, 56(11), 1621-1633. http://dx.doi.org/10.1016/j.addr.2004.05.002. PMid:15350292.

16. Krawczak, P. (2013). Medical plastics: serving healthcare. Express Polymer Letters, 7(8), 651-651. http://dx.doi.org/10.3144/expresspolymlett.2013.61.

17. Villanova, J. C. O., Oréfice, R. L., & Cunha, A. S. (2010). Pharmaceutical applications of polymers. Polímeros: Ciência e Tecnologia, 20(1), 51-64. http://dx.doi.org/10.1590/S0104-14282010005000009.

18. Severino, P., Santana, M. H. A., Pinho, S. C., & Souto, E. B. (2011). Polímeros sintéticos biodegradáveis: matérias-primas e métodos de produção de micropartículas para uso em drug delivery e liberação controlada. Polímeros: Ciência e Tecnologia, 21(4), 286-292. http://dx.doi.org/10.1590/S0104-14282011005000060.

19. Severino, P., Santana, M. H. A., Malmonge, S. M., & Souto, E. B. (2011). Polímeros usados como sistemas de transporte de princípios ativos. Polímeros: Ciência e Tecnologia, 21(5), 361-368. http://dx.doi.org/10.1590/S0104-14282011005000061.

20. Saez, V., Ramón, J., Peniche, C., & Hardy, E. (2012). Microencapsulation of Alpha Interferons in Biodegradable Microspheres. Journal of Interferon & Cytokine Research, 32(7), 299-311. http://dx.doi.org/10.1089/jir.2011.0034. PMid:22774794.

21. Nkabinde, L. A. (2013). Poly (D,L-lactide-co-glycolide) nanoparticles: Uptake by epithelial cells and cytotoxicity. Express Polymer Letters, 8(3), 197-206. http://dx.doi.org/10.3144/expresspolymlett.2014.23.

22. Hamad, K. (2015). Properties and Medical Applications of Polylactic Acid: A Review. Express Polymer Letters, 9(5), 435-455. http://dx.doi.org/10.3144/expresspolymlett.2015.42.

23. Ke, Y. (2014). Preparation of carboxymethyl cellulose based microgels for cell encapsulation. Express Polymer Letters, 8(11), 841-849. http://dx.doi.org/10.3144/expresspolymlett.2014.85.

24. Uhrich, K. E., Cannizzaro, S. M., Langer, R. S., & Shakesheff, K. M. (1999). Polymeric systems for controlled drug release. Chemical Reviews, 99(11), 3181-3198. http://dx.doi.org/10.1021/cr940351u. PMid:11749514.

25. Corrigan, O. I., & Li, X. (2009). Quantifying drug release from PLGA nanoparticulates. European Journal of Pharmaceutical Sciences, 37(3-4), 477-485. http://dx.doi.org/10.1016/j.ejps.2009.04.004. PMid:19379812.

26. Letchford, K., & Burt, H. (2007). A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes. European Journal of Pharmaceutics and Biopharmaceutics, 65(3), 259-269. http://dx.doi.org/10.1016/j.ejpb.2006.11.009. PMid:17196803.

27. Pereira, E. D., Souza, F. G. Jr., Pinto, J. C., Cerruti, R., & Santana, C. I. (2015). Synthesis, characterization and drug delivery profile of magnetic PLGA-PEG-PLGA/maghemite nanocomposite. Macromolecular Symposia, (in press).

28. Song, Z., Feng, R., Sun, M., Guo, C., Gao, Y., Li, L., & Zhai, G. (2011). Curcumin-loaded PLGA-PEG-PLGA triblock copolymeric micelles: preparation, pharmacokinetics and distribution in vivo. Journal of Colloid and Interface Science, 354(1), 116-123. http://dx.doi.org/10.1016/j.jcis.2010.10.024. PMid:21044788.

29. Pereira, E., Souza, F. Jr., Santana, C. i., Soares, D., Lemos, A., & Menezes, L. (2013). Influence of magnetic field on the dissolution profile of cotrimoxazole inserted into poly(lactic acid-co-glycolic acid) and maghemite nanocomposites. Polymer Engineering and Science, 53(11), 2308-2317. http://dx.doi.org/10.1002/pen.23606.

30. Ferreira, L. P., Moreira, A. N., Delazare, T., Oliveira, G. E., & Souza, F. G., Jr. (2012). Petroleum absorbers based on CNSL, furfural and lignin – the effect of the chemical similarity on the interactions among petroleum and bioresins. Macromolecular Symposia, 319(1), 210-221. http://dx.doi.org/10.1002/masy.201100145.

31. Jeong, B., Bae, Y. H., & Kim, S. W. (1999). Biodegradable thermosensitive micelles of PEG-PLGA-PEG triblock copolymers. Colloids and Surfaces. B, Biointerfaces, 16(1-4), 185-193. http://dx.doi.org/10.1016/S0927-7765(99)00069-7.

32. Li, Y., Pei, Y., Zhang, X., Gu, Z., Zhou, Z., Yuan, W., Zhou, J., Zhu, J., & Gao, X. (2001). PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats. Journal of Controlled Release, 71(2), 203-211. http://dx.doi.org/10.1016/S0168-3659(01)00218-8. PMid:11274752.

33. Wang, H., Zhao, Y., Wu, Y., Hu, Y. L., Nan, K., Nie, G., & Chen, H. (2011). Enhanced anti-tumor efficacy by co-delivery of doxorubicin and paclitaxel with amphiphilic methoxy PEG-PLGA copolymer nanoparticles. Biomaterials, 32(32), 8281-8290. http://dx.doi.org/10.1016/j.biomaterials.2011.07.032. PMid:21807411.

34. Qiao, M., Chen, D., Hao, T., Zhao, X., Hu, H., & Ma, X. (2007). Effect of bee venom peptide-copolymer interactions on thermosensitive hydrogel delivery systems. International Journal of Pharmaceutics, 345(1-2), 116-124. http://dx.doi.org/10.1016/j.ijpharm.2007.05.056. PMid:17629639.

35. Saadati, R., & Dadashzadeh, S. (2014). Marked effects of combined TPGS and PVA emulsifiers in the fabrication of etoposide-loaded PLGA-PEG nanoparticles: in vitro and in vivo evaluation. International Journal of Pharmaceutics, 464(1-2), 135-144. http://dx.doi.org/10.1016/j.ijpharm.2014.01.014. PMid:24451238.

36. Yang, A., Yang, L., Liu, W., Li, Z., Xu, H., & Yang, X. (2007). Tumor necrosis factor alpha blocking peptide loaded PEG-PLGA nanoparticles: Preparation and in vitro evaluation. International Journal of Pharmaceutics, 331(1), 123-132. http://dx.doi.org/10.1016/j.ijpharm.2006.09.015. PMid:17097246.

37. Martín-Banderas, L., Muñoz-Rubio, I., Álvarez-Fuentes, J., Durán-Lobato, M., Arias, J. L., Holgado, M. Á., & Fernández-Arévalo, M. (2014). Engineering of Δ9-tetrahydrocannabinol delivery systems based on surface modified-PLGA nanoplatforms. Colloids and Surfaces. B, Biointerfaces, 123, 114-122. http://dx.doi.org/10.1016/j.colsurfb.2014.09.002. PMid:25262411.

38. Jain, A., Jain, S. K., Ganesh, N., Barve, J., & Beg, A. M. (2010). Design and development of ligand-appended polysaccharidic nanoparticles for the delivery of oxaliplatin in colorectal cancer. Nanomedicine, 6(1), 179-190. http://dx.doi.org/10.1016/j.nano.2009.03.002. PMid:19447205.

39. Kelley, K., & Lai, K. (2011). Accuracy in parameter estimation for the root mean square error of approximation: sample size planning for narrow confidence intervals. Multivariate Behavioral Research, 46(1), 1-32. http://dx.doi.org/10.1080/00273171.2011.543027. PMid:26771579.

40. Brownlee, K. (1984). Statistical theory and methodology in science and engineering. Malabar: Krieger Pub. Co.; 1984.

41. Corrigan, D., Healy, A., & Corrigan, O. (2002). The effect of spray drying solutions of polyethylene glycol (PEG) and lactose/PEG on their physicochemical properties. International Journal of Pharmaceutics, 235(1-2), 193-205. http://dx.doi.org/10.1016/S0378-5173(01)00990-5. PMid:11879754.

42. Peppas, N. A., & Narasimhan, B. (2014). Mathematical models in drug delivery: how modeling has shaped the way we design new drug delivery systems. Journal of Controlled Release, 190, 75-81. http://dx.doi.org/10.1016/j.jconrel.2014.06.041. PMid:24998939.

43. Ritger, P., & Peppas, N. (1987). A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or disks. Journal of Controlled Release, 5(1), 23-36. http://dx.doi.org/10.1016/0168-3659(87)90034-4.

44. Jeong, J. H., Lim, D. W., Han, D. K., & Park, T. G. (2000). Synthesis, characterization and protein adsorption behaviors of PLGA/PEG di-block co-polymer blend films. Colloids and Surfaces. B, Biointerfaces, 18(3-4), 371-379. http://dx.doi.org/10.1016/S0927-7765(99)00162-9. PMid:10915958.

45. Peppas, N., & Sahlin, J. (1989). A simple equation for the description of solute release. III. Coupling of diffusion and relaxation. International Journal of Pharmaceutics, 57(2), 169-172. http://dx.doi.org/10.1016/0378-5173(89)90306-2.

46. Ritger, P., & Peppas, N. (1987). A simple equation for description of solute release II. Fickian and anamolous release from swellable devices. Journal of Controlled Release, 5(1), 37-42. http://dx.doi.org/10.1016/0168-3659(87)90035-6.
588371d77f8c9d0a0c8b4aae polimeros Articles
Links & Downloads

Polímeros: Ciência e Tecnologia

Share this page
Page Sections