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Current Nanomedicine

Editor-in-Chief

ISSN (Print): 2468-1873
ISSN (Online): 2468-1881

Research Article

Formulation and Characterization of Gefitinib-loaded Polymeric Nanoparticles Using Box-Behnken Design

Author(s): M. Gupta, R.K. Marwaha and H. Dureja*

Volume 9, Issue 1, 2019

Page: [46 - 60] Pages: 15

DOI: 10.2174/2468187308666180815145350

Price: $65

Abstract

Background: Nanotechnology has considerably modified the treatment of cancer by overcoming the prevailing drawbacks in conventional chemotherapy like severe systemic side effects, undesirable bio-distribution and drug resistance.

Objective: The objective behind the present study was to develop polymeric nanoparticles loaded with gefitinib by ionic gelation method and optimize the prepared nanoparticles using Box-Behnken Design at 3-factors and 3-levels. The main and interactive effects of three selected process variables i.e chitosan concentration, sodium tripolyphosphate (NaTPP) concentration and NaTPP volume on the encapsulation efficiency and % cumulative drug release were determined.

Method: Seventeen nanoparticle formulations were prepared by ionic gelation method using chitosan concentration (0.1-0.3% w/v), NaTPP concentration (0.2-0.6% w/v) and NaTPP volume (8-12 ml) applying Box-behnken design. The cryoprotectant used was 5% w/v trehalose. The nanoparticle formulations were further evaluated for various parameters.

Results: The formulation (NP-5) prepared using chitosan (0.1% w/v) and NaTPP (0.4% w/v ) in 8 ml volume exhibited particle size (79.4 nm), polydispersity index (0.349), encapsulation efficiency (82.05 %) and % cumulative drug released (40.83 %) in phosphate buffer (pH 6.8) over a period of 24 h. The release mechanism followed was higuchi model. The values of various evaluation parameters observed were found to be in close concurrence with the values predicted employing the Design expert software.

Conclusion: The nanoparticle formulation obtained using chitosan in low concentration, optimum concentration ratio of chitosan: NaTPP along with low volume of NaTPP showed desired features. The mathematical models were further designed to develop polymeric nanoparticles with required characteristics.

Keywords: Box-behnken design, gefitinib, nanoparticles, sodium tripolyphosphate, chitosan, trehalose, ionic gelation method.

Graphical Abstract

[1]
Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer 2017; 17: 20-37.
[2]
Haley B, Frenkel E. Nanoparticles for drug delivery in cancer treatment. Urol Oncol 2008; 26(1): 57-64.
[3]
Cho K, Wang X, Nie S, Chen ZG, Shin DM. Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 2008; 14(5): 1310-6.
[4]
Gu FX, Karnik R, Wang AZ, et al. Targeted nanoparticles for cancer therapy. Nano Today 2007; 2(3): 14-21.
[5]
Sinha R, Kim GJ, Nie S, Shin DM. Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery. Mol Cancer Ther 2006; 5(8): 1909-17.
[6]
Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev 2008; 60(15): 1615-26.
[7]
Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul 2001; 41: 189-207.
[8]
Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000; 407(6801): 249-57.
[9]
Cleared nanoparticles for medical use. (Accessed on March 04, 2017) Available at: https://nanohybrids.net/ pages/cleared-nanoparticles-for-medical-use
[10]
Babu A, Templeton AK, Munshi A, Ramesh R. Nanoparticle based drug delivery for therapy of lung cancer: progress and challenges. J Nanomat 2013; 2013: 1-11.
[11]
Ni XL, Chen LX, Zhang H, et al. 2017 In vitro and in vivo antitumor effect of gefitinib nanoparticles on human lung cancer. Drug Deliv 2017; 24(1): 1501-12.
[12]
Lee WH, Loo CY, Young PM, et al. Recent advances in curcumin nanoformulation for cancer therapy. Expert Opin Drug Deliv 2014; 11: 1183-201.
[13]
Wakeling AE, Guy SP, Woodburn JR, et al. ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res 2002; 62(20): 5749-54.
[14]
Gupta M, Goswami K, Marwaha RK, Dureja H. Safety and antitumor activity of gefitinib: an overview. Int J Pharm Sci Res 2014; 5(11): 4129-40.
[15]
Cohen MH, Williams GA, Sridhara R, et al. United States Food and Drug Administration drug approval summary gefitinib (ZD1839; Iressa) tablets. Clin Cancer Res 2004; 10(4): 1212-8.
[16]
Tikoo K, Kaur J. p300/CBP dependent hyperacetylation of histone potentiates anticancer activity of gefitinib nanoparticles. Biochimica et Biophysica Acta 2013; 1833: 1028-40.
[17]
Johan C, Katarina E, Roger P, Katarina J. Rheological evaluation of Gelrite in situ gels for ophthalmic use. Eur J Pharm Sci 1998; 6: 113-9.
[18]
Kesarla R, Tonk T, Vora PA, Shah T, Parmar S. Preparation and evaluation of nanoparticles loaded ophthalmic in situ gel. Drug Deliv 2016; 23(7): 2363-70.
[19]
Sworn G, Sanderson GR, Gibson W. Gellan gum fluid gels. Food Hydrocolloids 1995; 9(4): 265-71.
[20]
Anwunobi AP, Emeje MO. Recent Applications of natural polymers in nanodrug delivery. J Nanomed Nanotechnol 2011; S4(02): 1-6.
[21]
Kurlyandskaya GV, Litvinova LS, Safronov AP, et al. Water based suspensions of iron oxide nanoparticles with electrostatic or steric stabilization by chitosan: fabrication, characterization and biocompatibility. Sensors 2017; 17: 2605.
[22]
Kuo CH, Liu YC, Chang CJ, Chen JH, Chang C, Shieh CJ. Optimum conditions for lipase immobilization on chitosan-coated Fe3O4 nanoparticles. Carbohydrate Polymers 2012; 87(4): 2538-45.
[23]
Yuan Q. Hein S, Misra RD. New generation of chitosan-encapsulated ZnO quantum dots loaded with drug: synthesis, characterization and in vitro drug delivery response. Acta Biomater 2010; 6(7): 2732-9.
[24]
Kouchak M, Avadi M, Abbaspour M, Jahangiri A, Boldaji SK. Effect of different molecular weights of chitosan on preparation and characterization of insulin loaded nanoparticles by ion gelation method. Int J Drug Dev Res 2012; 4(2): 271-7.
[25]
Gupta M, Marwaha RK, Dureja H. Development and characterization of gefitinib loaded polymeric nanoparticles by ionic gelation method. Pharmaceut Nanotechnol 2017; 5: 301-9.
[26]
Nagarajan E, Shanmugasundaram P. Ravichan diran V, Vijayalakshmi A, Senthilnathan B, Masilaman K. Development and evaluation of chitosan based polymeric nanoparticles of an antiulcer drug lansoprazole. J Appl Pharm Sci 2015; 5(04): 20-5.
[27]
Seifirad S, Karami H, Shahsavari S, Mirabbasi F, Dorkoosh FA. Design and characterization of mesalamine loaded nanoparticles for controlled delivery system. Nanomed Res J 2016; 1(2): 97-106.
[28]
Monograph on Gefitinib. In: Indian Pharmacopoeia. 6th ed. The Indian Pharmacopoeia Commission, Ghaziabad, Vol II 2010; p. 1405.
[29]
Calvo P, Remunan Lopez C, Vila Jato JL, Alonso MJ. Chitosan and chitosan/ethylene oxide-propylene oxide block copolymer nanoparticles as novel carriers for proteins and vaccines. Pharm Res 1997; 14: 1431-6.
[30]
Reddy HL, Murthy RSR. Etoposide loaded nanoparticles made from glyceride lipids: formulation, characterization, in vitro drug release and stability evaluation. AAPS PharmSciTech 2005; 6(2): E158-66.
[31]
Correia Pinto JF, Csaba N, Schiller JT, Alonso MJ. Chitosan-poly (I:C)-Padre based nano- particles as delivery vehicles for synthetic peptide vaccines. Vaccines 2015; 3: 730-50.
[32]
Nallamuthu I, Devi A, Khanum F. Chlorogenic acid loaded chitosan nanoparticles with sustained release property, retained antioxidant activity and enhanced bioavailability. Asian J Pharm Sci 2015; 10(3): 203-11.
[33]
Guidelines for dynamic light scattering measurement and analysis. (Accessed on: May 12, 2016) Available at: http://50.87.149.212/sites/default/files/nanoComposix%20Guidelines%20Analysis.pdf.
[34]
Dissolution methods. U.S. Food and Drug Administration. (Accessed on June 15, 2016) Available at: https://www.accessdata.fda.gov/scripts/cder/ dissolution/dsp_getallData.cfm
[35]
Mohammad M, Graeme G, Kenneth B. Effects of chemical conjugation of L-leucine to chitosan on dispersibility and controlled release of drug from a nanoparticulate dry powder inhaler formulation. Mol Pharm 2016; 13(5): 1455-66.
[36]
Grossman JH, McNeil SE. Nanoparticles in cancer medicine. Physics Today 2012; 3: 730-50.
[37]
Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983; 15(1): 25-35.
[38]
Srinivas NSK, Verma R, Kulyadi GP, Kumar L. A quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro, and in vivo characterization. Int J Nanomed 2017; 12: 15-28.

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