Encapsulation of irinotecan in polymeric nanoparticles: Characterization, release kinetic and cytotoxicity evaluation

Document Type : Research Paper

Authors

1 Novel Drug Delivery Systems Lab, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

2 Medical Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran , Iran

3 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

4 Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran

Abstract

Objective(s): Irinotecan is a potent anti-cancer drug from camptothecin group which inhibits topoisomerase I. Recently, biodegradable and biocompatible polymers such as poly lactide-co-glycolides (PLGA) have been considered for the preparation of nanoparticles (NPs).
Materials and Methods: In this study, irinotecan loaded PLGA NPs were fabricated by an emulsification/solvent diffusion method to improve the efficacy of irinotecan. The effect of several parameters on the NPs’ characteristics was assessed, including the amount of drug and polymer, the amount and volume of the poly vinyl alcohol as a surfactant, and also the internal-phase volume/composition. The irinotecan entrapment efficiency and the particle size distribution were optimized by changing these variables. The cytotoxicity of the particles was evaluated by cell viability assay.
Results: NPs were spherical with a comparatively mono-dispersed size distribution and negative zeta potential. Selected formulation (S9) showed suitable size distribution about120 nm with relative high drug entrapment. MTT assay showed a stronger cytotoxicity of S9 against HT-29 cancer cells than control NPs and irinotecan free drug. The release kinetic indicated Log-Probability model in S9.
Conclusion: Our results demonstrated that the designed NPs show suitable characteristic and also great potential for further in vivo cancer evaluation.

Keywords

References

[1] Mathieson RHJ, Loos WJ, Verweij J and Sparreboom A. Pharmacology of Topoisomerase I Inhibitors Irinotecan (CPT-11) and Topotecan. Curr Cancer Drug Targets. 2002; 2: 103-123.
[2] Mohajer M, Khameneh B, Tafaghodi M. Preparation and characterization of PLGA nanospheres loaded with inactivated influenza virus, CpG-ODN and Quillaja saponin. IJBMS. 2014;17(9):722-726.
[3] Onishi H, MachidaYandMachidaY. Antitumor properties of irinotecan-containing nanoparticles prepared using poly (DL-lactic acid) and poly (ethylene glycol)-blockpoly (propylene glycol)-block-poly (ethylene glycol). Biol Pharm Bull. 2003; 26: 116-119.
[4] Ebrahimnejad P, Dinarvand R, Sajadi SA, Jafari MR, Movaghari F, Atyabi F. Development and validation of an ion-pair HPLC chropmatography for simultaneous determination of lactone and carboxylate forms of SN-38 in nanoparticles. J Food Drug Anal. 2009; 17: 246-256.
[5] Kunii R, Onishi H, Ueki K, Koyama K, Machida Y. Particle characteristics and biodistribution of camptothecin-loaded PLA/(PEG-PPG-PEG) nanoparticles. Drug deliv. 2008; 15: 3-10.
[6] Ebrahimnejad P, Dinarvand R, Sajadi SA, Atyabi F, Ramezani F, Jafari MR. Preparation and characterization of poly lactide-co-glycolide nanoparticles of SN-38. PDA J Pharm Sci Technol. 2009; 63: 512-520.
[7] Oguma T. Antitumor drug processing topoisomerase I inhibition: applicable separation methods. J Chromatogr B. 2001; 764: 49-458.
[8] Sano K, Yoshikawa M, Hayasaka S, Satake K, Ikegami Y, Yoshida H, Ishikawa T. and Tanabe S. Simple non-ion-paired high-performance liquid chromatographic method for simultaneous quantitation of C and L forms of 14 new camptothecin derivatives. J Chromatogr B. 2003; 795: 25-34.
[9] Esmaeili F, Atyabi F, Dinarvand, R. Preparation and characterization of estradiol-loaded PLGA nanoparticles using homogenization-solvent diffusion method. Daru. 2008; 16: 196-202.
[10] Kim SH, Jeong JH, Chun KW, Park TG, Target-specific cellular uptake of PLGA nanoparticles coated with poly(L-lysine)-poly(ethylene glycol)-folate conjugate. Langmuir. 2005; 21: 8852-8857.
[11] Ebrahimnejad P, Dinarvand R, Sajadi A, Jaafari MR, Nomani AR, Azizi E, Malekshahi MR, Atyabi F. Preparation and in vitro evaluation of actively targetable nanoparticles for SN-38 delivery against HT29 cell lines. Nanomedicine. 2010; 6: 478-485.
[12] Singh R, Jr JWL. Nanoparticle-based targeted drug delivery. Exp Mol Pathol. 2009; 86: 215–223.
[13] Paruchuri R, Trivedi Sh, Joshi SV, Pavuluri G, Kumar MS. Formulation. Optimization and characterization of irinotecan nanoparticles.  IJPCBS. 2012; 2(1): 1-10.
[14] Danhier F, Lecouturier N, Vroman B, Jérôme C, Marchand-Brynaert J, Feron O, Préat V. Paclitaxel-loaded PEGylated PLGA-based nanoparticles: In vitro and in vivo evaluation. J Control Rel. 2009; 133: 11–17.
[15] Mohammadi A, Esmaeili F, Dinarvand R, Atyabi F, Walker RB. Simultaneous determination of irinotecan hydrochloride and its related compounds by high performance liquid chromatography using ultraviolet detection. Asian J Chem. 2010; 22: 3966-3972.
[16] Peppas NA. Analysis of fickian and non-fickian drug release from polymers.  Pharm Acta Helv. 1985; 60:110-111.
[17] Barzegar-Jalali, M. Kinetic analysis of drug release from nanoparticles. J Pharm Sci. 2008; 11(1): 167-177.
[18] Arica B, Lamprecht A. In vitro evaluation of betamethasone-loaded nanoparticles. Drug Dev Ind Pharm. 2005; 31: 19 –24.
[19] Sharma A, Pandey R, Sharma S, Khuller GK. Chemotherapeutic efficacy of poly (DL-lactide-co-glycolide) nanoparticle encapsulated antitubercular drugs at sub-therapeutic dose against experimental tuberculosis. Int J Antimicrob Agents. 2004; 24: 599–604.
[20] Alex R, Bodmeier R. Encapsulation of water-soluble drugs by a modified solvent evaporation method. I. Effect of process and formulation variables on drug entrapment. J Microencaps.1990;7:347-355.
[21] Loveymi BD, Jelvehgari M, Zakeri-Milani P, Valizadeh H. Statistical Optimization of Oral Vancomycin-Eudragit RS Nanoparticles Using Response Surface Methodology.  IJPS. 2012; 11 (4): 1001-1012.
[22] Guo S, Zhang X, Gan L, Zhu C, Gan Y. Effect of poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) micelles on pharmacokinetics and intestinal toxicity of irinotecan hydrochloride: potential involvement of breast cancer resistance protein (ABCG2). J Pharm Pharmacol. 2010; 62(8): 973-984.
[23] Ricci M, Blasi P, Giovagnoli S, Perioli L, Vescovi C, Rossi C.Leucinostatin-A loaded nanospheres: characterization and in vivo toxicity and efficacy evaluation. Int J Pharm. 2004; 275: 61-72.
[24] Kato K, Chin K, Yoshikawa T, Yamaguchi K, Tsuji Y, Esaki T, et al. Phase II study of NK105, a paclitaxel-incorporating micellar nanoparticle, for previously treated advanced or recurrent gastric cancer. Invest New Drugs. 2012; 30(4): 1621-167.
[25] Tian G, Zheng X, Zhang X, Yin W, Yu J, Wang D, Zhang Z, Yang X, Gu Z, Zhao Y.TPGS-stabilized NaYbF 4: Er upconversion nanoparticles for dual-modal fluorescent/CT imaging and anticancer drug delivery to overcome multi-drug resistance. Biomaterials. 2015; 40: 107-116.
[26] Acharya S, Sahoo SK. PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev. 2011; 63 (3): 170-183.
[27] Liu Y, Schwendeman SP. Mapping microclimate pH distribution inside protein-encapsulated PLGA microspheres using confocal laser scanning microscopy. Mol Pharm. 2012; 9 (5): 1342-1350.
[28] Tacar O, Sriamornsak P, Dass CR. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol. 2013; 65(2): 157-170.
[29] Mosallaei N, Jaafari MR, Hanafi Bojd MY, Golmohammadzadeh S, Malaekeh Nikouei B. Docetaxel loaded solid lipid nanoparticles: Preparation, characterization, in vitro, and in vivo evaluations. J Pharm Sci. 2013; 102(6): 1994-2004.
Nanomedicine Journal
Volume 3, Issue 3
July 2016
Pages 159-168

Files

Share

How to cite

Statistics