DOI QR코드

DOI QR Code

Synthesis, Characterization and in vitro Anti-Tumoral Evaluation of Erlotinib-PCEC Nanoparticles

  • Barghi, Leila (Faculty of Pharmacy, Tabriz University of Medical Sciences) ;
  • Asgari, Davoud (Faculty of Pharmacy, Tabriz University of Medical Sciences) ;
  • Barar, Jaleh (Faculty of Pharmacy, Tabriz University of Medical Sciences) ;
  • Nakhlband, Aylar (Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences) ;
  • Valizadeh, Hadi (Faculty of Pharmacy, Tabriz University of Medical Sciences)
  • 발행 : 2015.01.06

초록

Background: Development of a nanosized polymeric delivery system for erlotinib was the main objective of this research. Materials and Methods: Poly caprolactone-polyethylene glycol-polycaprolactone (PCEC) copolymers with different compositions were synthesized via ring opening polymerization. Formation of triblock copolymers was confirmed by HNMR as well as FT-IR. Erlotinib loaded nanoparticles were prepared by means of synthesized copolymers with solvent displacement method. Results: Physicochemical properties of obtained polymeric nanoparticles were dependent on composition of used copolymers. Size of particles was decreased with decreasing the PCL/PEG molar ratio in used copolymers. Encapsulation efficiency of prepared formulations was declined by decreasing their particle size. Drug release behavior from the prepared nanoparticles exhibited a sustained pattern without a burst release. From the release profiles, it can be found that erlotinib release rate from polymeric nanoparticles is decreased by increase of CL/PEG molar ratio of prepared block copolymers. Based on MTT assay results, cell growth inhibition of erlotinib has a dose and time dependent pattern. After 72 hours of exposure, the 50% inhibitory concentration (IC50) of erlotinib hydrochloride was appeared to be $14.8{\mu}M$. Conclusions: From the obtained results, it can be concluded that the prepared PCEC nanoparticles in this study might have the potential to be considered as delivery system for erlotinib.

키워드

참고문헌

  1. Aydiner A, Yildiz I, Seyidova A (2013). Clinical outcomes and prognostic factors associated with the response to erlotinib in non-small-cell lung cancer patients with unknown EGFR mutational status. Asian Pac J Cancer Prev, 14, 3255-61. https://doi.org/10.7314/APJCP.2013.14.5.3255
  2. Barghi L, Aghanejad A, Valizadeh H, et al (2012). Modified synthesis of erlotinib hydrochloride. Adv Pharm Bull, 2, 119-22.
  3. Bogdanov B, Vidts A, Van Den Buicke A, et al (1998). Synthesis and thermal properties of poly(ethylene glycol)-poly(I${\mu}$-caprolactone) copolymers. Polymer, 39, 1631-6. https://doi.org/10.1016/S0032-3861(97)00444-8
  4. Bolandnazar S, Divsalar A, Valizadeh H, et al (2013). Development and Application of an HPLC Method for Erlotinib Protein Binding Studies. Adv Pharm Bull, 19, 22.
  5. Clay D, Lipman YM, Bonk ME (2005). Erlotinib (Tarceva(R)): A brief overview, P and T, 30, 561-602.
  6. Dubey N, Varshney R, Shukla J, et al (2012). Synthesis and evaluation of biodegradable PCL/PEG nanoparticles for neuroendocrine tumor targeted delivery of somatostatin analog. Drug Deliv, 19, 132-42. https://doi.org/10.3109/10717544.2012.657718
  7. Fonseca C, Simoes S, Gaspar R (2002). Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J Controlled Release, 83, 273-86. https://doi.org/10.1016/S0168-3659(02)00212-2
  8. Freiberg S, Zhu XX (2004). Polymer microspheres for controlled drug release. Int J Pharmaceutics, 282, 1-18. https://doi.org/10.1016/j.ijpharm.2004.04.013
  9. Gale DM (2003). Molecular targets in cancer therapy. Seminars Oncol Nurs, 19, 193-205. https://doi.org/10.1016/S0749-2081(03)00047-0
  10. Galindo-Rodriguez S, Allemann E, Fessi H, et al (2004). Physicochemical parameters associated with nanoparticle formation in the salting-out, emulsification-diffusion, and nanoprecipitation methods. Pharm Res, 21, 1428-39. https://doi.org/10.1023/B:PHAM.0000036917.75634.be
  11. Ge H, Hu Y, Jiang X, et al (2002). Preparation, characterization, and drug release behaviors of drug nimodipine-loaded poly(${\varepsilon}$-caprolactone)-poly(ethylene oxide)-poly(${\varepsilon}$-caprolactone) amphiphilic triblock copolymer micelles. J Pharmaceutical Sciences, 91, 1463-73. https://doi.org/10.1002/jps.10143
  12. Ge H, Hu Y, Yang S, et al (2000). Preparation, characterization, and drug release behaviors of drug-loaded ${\varepsilon}$-caprolactone/Llactide copolymer nanoparticles. J Appl Polymer Sci 75, 874-82. https://doi.org/10.1002/(SICI)1097-4628(20000214)75:7<874::AID-APP3>3.0.CO;2-G
  13. Kim SY, Lee YM (2001). Taxol-loaded block copolymer nanospheres composed of methoxy poly(ethylene glycol) and poly(${\varepsilon}$-caprolactone) as novel anticancer drug carriers. Biomaterials, 22, 1697-704. https://doi.org/10.1016/S0142-9612(00)00292-1
  14. Kingsley J, Dou H, Morehead J, et al (2006). Nanotechnology: A Focus on Nanoparticles as a Drug Delivery System. J Neuroimmune Pharmacol, 1, 340-50. https://doi.org/10.1007/s11481-006-9032-4
  15. Letchford K, Burt H (2007). A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes. Eur JPharmaceutics Biopharmaceutics, 65, 259-69. https://doi.org/10.1016/j.ejpb.2006.11.009
  16. Liu CB, Gong CY, Huang MJ, et al (2008). Thermoreversible gel-sol behavior of biodegradable PCL-PEG-PCL triblock copolymer in aqueous solutions. J Biomedical Materials Res Part B: Applied Biomaterials, 84, 165-75.
  17. Lu Z, Bei J, Wang S (1999). A method for the preparation of polymeric nanocapsules without stabilizer. J Controlled Release, 61, 107-12. https://doi.org/10.1016/S0168-3659(99)00112-1
  18. Maeda H, Wu J, Sawa T, et al (2000). Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release, 65, 271-84. https://doi.org/10.1016/S0168-3659(99)00248-5
  19. Makrilia N, Lappa T, Xyla V, et al (2009). The role of angiogenesis in solid tumours: An overview. European Journal of Internal Medicine, 20, 663-71. https://doi.org/10.1016/j.ejim.2009.07.009
  20. Marslin G, Sheeba CJ, Kalaichelvan VK, et al (2009). Poly(D,Llactic-co-glycolic acid) nanoencapsulation reduces Erlotinibinduced subacute toxicity in rat. J Biomed Nanotechnol, 5, 464-71. https://doi.org/10.1166/jbn.2009.1075
  21. Merkli A, Tabatabay C, Gurny R, et al (1998). Biodegradable polymers for the controlled release of ocular drugs. Progress Polymer Science, 23, 563-80. https://doi.org/10.1016/S0079-6700(97)00048-8
  22. Molpeceres J, Guzman M, Aberturas MR, et al (1996). Application of central composite designs to the preparation of polycaprolactone nanoparticles by solvent displacement. J Pharmaceutical Sciences, 85, 206-13. https://doi.org/10.1021/js950164r
  23. Mondal N, Samanta A, Pal TK, et al (2008). Effect of different formulation variables on some particle characteristics of poly (DL-lactide-co-glycolide) nanoparticles. Yakugaku Zasshi, 128, 595-601. https://doi.org/10.1248/yakushi.128.595
  24. Nair LS, Laurencin CT (2007). Biodegradable polymers as biomaterials. Progress in Polymer Science, 32, 762-98. https://doi.org/10.1016/j.progpolymsci.2007.05.017
  25. Nguyen THA (2010). Formation of nanoparticles in aqueous solution from poly (${\varepsilon}$-caprolactone)-poly (ethylene glycol)-poly (${\varepsilon}$--caprolactone). Adv Natural Sciences: Nanoscience Nanotechnology, 1, 025012. https://doi.org/10.1088/2043-6254/1/2/025012
  26. Okada M (2002). Chemical syntheses of biodegradable polymers. Progress in Polymer Science, 27, 87-133.
  27. Pereira Ade F, Pereira LG, Barbosa LA, et al (2013). Efficacy of methotrexate-loaded poly(epsilon-caprolactone) implants in Ehrlich solid tumor-bearing mice. Drug Deliv, 20, 168-79. https://doi.org/10.3109/10717544.2013.801052
  28. Pinto Reis C, Neufeld RJ, Ribeiro AnJ, et al (2006). Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles. Nanomedicine: Nanotechnology, Biology Medicine, 2, 8-21. https://doi.org/10.1016/j.nano.2005.12.003
  29. Qi WX, Shen Z, Lin F, et al (2012). Comparison of the efficacy and safety of EFGR tyrosine kinase inhibitor monotherapy with standard second-line chemotherapy in previously treated advanced non-small-cell lung cancer: a systematic review and meta-analysis. Asian Pac J Cancer Prev, 13, 5177-82. https://doi.org/10.7314/APJCP.2012.13.10.5177
  30. Quintanar-Guerrero D, Allemann E, Fessi H, et al (1998). Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers. Drug Dev Ind Pharm, 24, 1113-28. https://doi.org/10.3109/03639049809108571
  31. Ranson M, Shaw H, Wolf J, et al (2010). A phase I doseescalation and bioavailability study of oral and intravenous formulations of erlotinib (Tarceva$^{(R)}$, OSI-774) in patients with advanced solid tumors of epithelial origin. Cancer Chemotherapy Pharmacol, 66, 53-8. https://doi.org/10.1007/s00280-009-1133-3
  32. Ryu J-G, Jeong Y-I, Kim I-S, et al (2000). Clonazepam release from core-shell type nanoparticles of poly(${\varepsilon}$-caprolactone)/ poly(ethylene glycol)/poly(${\varepsilon}$--caprolactone) triblock copolymers. International J Pharmaceutics, 200, 231-42. https://doi.org/10.1016/S0378-5173(00)00392-6
  33. Ryu JG, Jeong YI, Kim YH, et al (2001). Preparation of core-shell type nanoparticles of poly(${\varepsilon}$-caprolactone)/poly(ethylene glycol)/poly(${\varepsilon}$-caprolactone) triblock copolymers. Bulletin of the Korean Chemical Society, 22, 467-75.
  34. Sanchez A, Vila-Jato JL, Alonso MJ (1993). Development of biodegradable microspheres and nanospheres for the controlled release of cyclosporin A. Int J Pharmaceutics, 99, 263-73. https://doi.org/10.1016/0378-5173(93)90369-Q
  35. Shenoy DB, Amiji MM (2005). Poly(ethylene oxide)-modified poly(${\varepsilon}$-caprolactone) nanoparticles for targeted delivery of tamoxifen in breast cancer. Int J Pharmaceutics, 293, 261-70. https://doi.org/10.1016/j.ijpharm.2004.12.010
  36. Sinha VR, Bansal K, Kaushik R, et al (2004). Poly-${\varepsilon}$-caprolactone microspheres and nanospheres: an overview. International J Pharmaceutics, 278, 1-23. https://doi.org/10.1016/j.ijpharm.2004.01.044
  37. Smith J (2005). Erlotinib: small-molecule targeted therapy in the treatment of non-small-cell lung cancer. Clin Ther, 27, 1513-34. https://doi.org/10.1016/j.clinthera.2005.10.014
  38. Soppimath KS, Aminabhavi TM, Kulkarni AR, et al (2001). Biodegradable polymeric nanoparticles as drug delivery devices. J Controlled Release, 70, 1-20. https://doi.org/10.1016/S0168-3659(00)00339-4
  39. Torchilin VP (2007). Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J, 9, 128-47. https://doi.org/10.1208/aapsj0902015
  40. Vicent MJ, Duncan R (2006). Polymer conjugates: nanosized medicines for treating cancer. Trends Biotechnol, 24, 39-47. https://doi.org/10.1016/j.tibtech.2005.11.006
  41. Vrignaud S, Hureaux J, Wack S, et al (2012). Design, optimization and in vitro evaluation of reverse micelleloaded lipid nanocarriers containing erlotinib hydrochloride. Int J Pharm, 436, 194-200. https://doi.org/10.1016/j.ijpharm.2012.06.026
  42. Wei X, Gong C, Gou M, et al (2009). Biodegradable poly(${\varepsilon}$-caprolactone)-poly(ethylene glycol) copolymers as drug delivery system. Int J Pharmaceutics, 381, 1-18. https://doi.org/10.1016/j.ijpharm.2009.07.033
  43. Woodruff MA, Hutmacher DW (2010). The return of a forgotten polymer-Polycaprolactone in the 21st century. Progr Polymer Science, 35, 1217-56. https://doi.org/10.1016/j.progpolymsci.2010.04.002
  44. Xu Y, Karmakar A, Heberlein WE, et al (2012). Multifunctional magnetic nanoparticles for synergistic enhancement of cancer treatment by combinatorial radio frequency thermolysis and drug delivery. Adv Healthc Mater, 1, 493-501. https://doi.org/10.1002/adhm.201200079
  45. Yadav D, Anwar MF, Garg V, et al (2014). Development of polymeric nanopaclitaxel and comparison with free paclitaxel for effects on cell proliferation of MCF-7 and B16F0 carcinoma cells. Asian Pac J Cancer Prev, 15, 2335-40. https://doi.org/10.7314/APJCP.2014.15.5.2335
  46. Yin HT, Zhang DG, Wu XL, et al (2013). In vivo evaluation of curcumin-loaded nanoparticles in a A549 xenograft mice model. Asian Pac J Cancer Prev, 14, 409-12. https://doi.org/10.7314/APJCP.2013.14.1.409
  47. Zhang L, He Y, Ma G, et al (2011). Paclitaxel-loaded polymeric micelles based on poly(${\varepsilon}$-caprolactone)-poly(ethylene glycol)-poly(${\varepsilon}$-caprolactone) triblock copolymers: in vitro and in vivo evaluation. Nanomedicine: Nanotechnology Biology Medicine, 8, 925-34.

피인용 문헌

  1. Overexpression of EGFR Protein in Bruneian Lung Cancer Patients vol.16, pp.1, 2015, https://doi.org/10.7314/APJCP.2015.16.1.233
  2. Inhibition of prostate cancer RM1 cell growth in vitro by hydroxyapatite nanoparticle-delivered short hairpin RNAs against Stat3 vol.16, pp.1, 2017, https://doi.org/10.3892/mmr.2017.6583
  3. Interaction of antitumoral drug erlotinib with biodegradable triblock copolymers: a molecular modeling study vol.72, pp.8, 2018, https://doi.org/10.1007/s11696-018-0413-y