Formulation, Characterization and In-vitro and In-vivo Evaluation of Capecitabine Loaded Niosomes

Page: [257 - 268] Pages: 12

  • * (Excluding Mailing and Handling)

Abstract

Background: Nanocarriers improve the efficacy of drugs by facilitating their specific delivery and protecting them from external environment resulting in a better performance against diseases.

Objective: In this study, it was aimed to improve the efficacy of capecitabine against colorectal cancer by its entrapment in niosomes. Ether injection method was used to prepare niosomes composed of span 20 and cholesterol.

Methods: Niosomes were evaluated by evaluating the entrapment efficiency, in-vitro drug release and cytotoxicity of capecitabine loaded niosomes. Niosomes were characterized by particle size analysis, transmission electron microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry for surface morphology and drug excipient interactions.

Results: High encapsulation efficiency (90.55%) was observed, which is anticipated to resolve the multi-drug resistance problem. Reported particle size was 180.9 + 5 nm with a negative zeta potential - 21 + 0.5 mV and the kinetic study showed a concentration-dependent release of the drug from the niosome. DSC study proved entrapment of the entire drug and its non-covalent bonding with the excipients. Cytotoxicity study of niosomes on CaCO2 cell line showed an improved IC50 value as compared to the free drug.

Conclusion: Enhanced cytotoxicity observed in the results further supports the suitability of niosome as a nanocarrier for pharmaceutical drug delivery.

Keywords: Niosomes, capecitabine niosomes, CaCO2 cell line, atomic force microscopy, differential scanning calorimeter, colorectal cancer.

Graphical Abstract

[1]
Zhao, S.; Yang, X.; Garamus, V.M.; Handge, U.A.; Bérengère, L.; Zhao, L.; Salamon, G.; Willumeit, R.; Zou, A.; Fan, S. Mixture of nonionic/ionic surfactants for the formulation of nanostructured lipid carriers: effects on physical properties. Langmuir, 2014, 30(23), 6920-6928.
[http://dx.doi.org/10.1021/la501141m] [PMID: 24832357]
[2]
Chandu, V.P.; Arunachalam, A.; Jeganath, S.; Yamini, K.; Tharangini, K.; Chaitanya, G. Niosomes: A novel drug delivery system. Int. J. Novel Trends Pharm. Sci., 2012, 2(1), 25-31.
[3]
Abdelkader, H.; Alani, A.W.; Alany, R.G. Recent advances in non-ionic surfactant vesicles (niosomes): self-assembly, fabrication, characterization, drug delivery applications and limitations. Drug Deliv., 2014, 21(2), 87-100.
[http://dx.doi.org/10.3109/10717544.2013.838077] [PMID: 24156390]
[4]
Gannu, P.K.; Pogaku, R. Nonionic surfactant vesicular systems for effective drug delivery-an overview. Acta Pharm. Sin. B, 2011, 1(4), 208-219.
[http://dx.doi.org/10.1016/j.apsb.2011.09.002]
[5]
Junyaprasert, V.B.; Teeranachaideekul, V.; Supaperm, T. Effect of charged and non-ionic membrane additives on physicochemical properties and stability of niosomes. AAPS PharmSciTech, 2008, 9(3), 851-859.
[http://dx.doi.org/10.1208/s12249-008-9121-1] [PMID: 18636334]
[6]
Kazi, K.M.; Mandal, A.S.; Biswas, N.; Guha, A.; Chatterjee, S.; Behera, M.; Kuotsu, K. Niosome: A future of targeted drug delivery systems. J. Adv. Pharm. Technol. Res., 2010, 1(4), 374-380.
[http://dx.doi.org/10.4103/0110-5558.76435] [PMID: 22247876]
[7]
Okore, V.C.; Attama, A.A.; Ofokansi, K.C.; Esimone, C.O.; Onuigbo, E.B. Formulation and evaluation of niosomes. Indian J. Pharm. Sci., 2011, 73(3), 323-328.
[PMID: 22457561]
[8]
Xin, Y.; Yin, M.; Zhao, L.; Meng, F.; Luo, L. Recent progress on nanoparticle-based drug delivery systems for cancer therapy. Cancer Biol. Med., 2017, 14(3), 228-241.
[http://dx.doi.org/10.20892/j.issn.2095-3941.2017.0052] [PMID: 28884040]
[9]
Rama, A.R.; Jimenez-Lopez, J.; Cabeza, L.; Jimenez-Luna, C.; Leiva, M.C.; Perazzoli, G.; Hernandez, R.; Zafra, I.; Ortiz, R.; Melguizo, C.; Prados, J. Last advances in nanocarriers-based drug delivery systems for colorectal cancer. Curr. Drug Deliv., 2016, 13(6), 830-838.
[http://dx.doi.org/10.2174/1567201813666151203232852] [PMID: 26634791]
[10]
Jadon, P.S.; Gajbhiye, V.; Jadon, R.S.; Gajbhiye, K.R.; Ganesh, N. Enhanced oral bioavailability of griseofulvin via niosomes. AAPS PharmSciTech, 2009, 10(4), 1186-1192.
[http://dx.doi.org/10.1208/s12249-009-9325-z] [PMID: 19856107]
[11]
Tamizharasi, S.; Dubey, A.; Rathi, V.; Rathi, J.C. Development and characterization of niosomal drug delivery of gliclazide. J. Young Pharm., 2009, 1(3), 205-209.
[http://dx.doi.org/10.4103/0975-1483.57065]
[12]
Mehta, S.K.; Jindal, N.; Kaur, G. Quantitative investigation, stability and in vitro release studies of anti-TB drugs in Triton niosomes. Colloids Surf. B Biointerfaces, 2011, 87(1), 173-179.
[http://dx.doi.org/10.1016/j.colsurfb.2011.05.018] [PMID: 21640561]
[13]
Vyas, S.P.; Venkatesan, N. Poly(phthaloyl-L-lysine)-coated multilamellar vesicles for controlled drug delivery: in vitro and in vivo performance evaluation. Pharm. Acta Helv., 1999, 74(1), 51-58.
[http://dx.doi.org/10.1016/S0031-6865(99)00016-3] [PMID: 10748624]
[14]
Moghimi, S.M.; Szebeni, J. Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog. Lipid Res., 2003, 42(6), 463-478.
[http://dx.doi.org/10.1016/S0163-7827(03)00033-X] [PMID: 14559067]
[15]
Arezoo, A.; Payam, K.; Abbas, P.; Moslem, L.N.; Amin, M. Preparation and characterization of formulation and in-vitro evaluation of capecitabine niosomes for the treatment of colon cancer. Int. J. Pharm. Sci. Res., 2015, 4(4), 1504-1513.
[16]
Sharma, V.; Anandhakumar, S.; Sasidharan, M. Self-degrading niosomes for encapsulation of hydrophilic and hydrophobic drugs: An efficient carrier for cancer multi-drug delivery. Mater. Sci. Eng. C, 2015, 56(56), 393-400.
[http://dx.doi.org/10.1016/j.msec.2015.06.049] [PMID: 26249606]
[17]
Khan, Y.; Durrani, S.K.; Siddique, M.; Mazhar, M. Hydrothermal synthesis of alpha Fe2O3 nanoparticles capped by tween-80. Mater. Lett., 2011, 65(14), 2224-2227.
[http://dx.doi.org/10.1016/j.matlet.2011.04.068]
[18]
Hug, S.J.; Bahnemann, D. Infrared spectra of oxalate, malonate and succinate adsorbed on the aqueous surface of rutile, anatase and lepidocrocite measured with in situ ATR-FTIR. J. Electron Spectrosc. Relat. Phenom., 2006, 150(2), 208-219.
[http://dx.doi.org/10.1016/j.elspec.2005.05.006]
[19]
Khan, Y.; Durrani, S.K.; Mehmood, M.; Ahmad, J.; Khan, M.R.; Firdous, S. Low temperature synthesis of fluorescent ZnO nanoparticles. Appl. Surf. Sci., 2010, 257(5), 1756-1761.
[http://dx.doi.org/10.1016/j.apsusc.2010.09.011]
[20]
Mobarak, H.M. Formulation, optimization and evaluation of Capecitabine tablet for colon specific drug delivery system. Int. J. Pharmaceut. Clin. Res., 2017, 9(7), 539-549.
[21]
Kaloustian, J.; Pauli, A.M.; Lechene, P.P.; Lafont, H.; Portugal, H. Thermal analysis of anhydrous and hydrated cholesterol. J. Therm. Anal. Calorim., 2003, 71(2), 341-351.
[http://dx.doi.org/10.1023/A:1022818902212]
[22]
Anbarasan, B.; Rekha, S.; Elango, K.; Shriya, B.; Ramaprabhu, S. Formulation and evaluation of proniosomal gel of capecitabine. Indo Am. J. Pharmaceut. Sci., 2013, 4(1), 6-19.
[23]
Jia, L.; Garza, M.; Wong, H.; Reimer, D.; Redelmeier, T.; Camden, J.B.; Weitman, S.D. Pharmacokinetic comparison of intravenous carbendazim and remote loaded carbendazim liposomes in nude mice. J. Pharm. Biomed. Anal., 2002, 28(1), 65-72.
[http://dx.doi.org/10.1016/S0731-7085(01)00702-6] [PMID: 11861109]
[24]
Pei, L.Y.; Soi, M.C.; Anna, P.K.L.; Rhun, Y.K. Niosome: A mini review on its structure, properties, methods of preparation and medical applications. J. Chem. Pharm. Res., 2016, 8(10), 231-239.
[25]
Namvaran, A.; Fazeli, M.; Farajnia, S.; Hamidian, G.; Rezazadeh, H. Apoptosis and caspase 3 pathway role on anti-proliferative effects of scrophulariaoxysepalamethanolic extract on CaCO-2 cells. Drug Res. (Stuttg.), 2017, 67(9), 547-552.
[http://dx.doi.org/10.1055/s-0043-110483] [PMID: 28628925]
[26]
Fathalla, D.; Abdel-Mageed, A.; Abdel-Hamid, F.; Ahmed, M. In-vitro and in-vivo evaluation of niosomal gel containing aceclofenac for sustained drug delivery. Int. J. Pharm. Sci. Res., 2014, 1, 105-111.
[27]
Shao, M.; Sun, S.L.; Li, M.H.; Li, B.X.; Yu, H.; Shen, Z.Y.; Ren, Y.C.; Hao, Z.F.; Chang, N.D.; Peng, H.S.; Yang, B.F. The liposomal daunorubicin plus tamoxifen: improving the stability, uptake, and biodistribution of carriers. J. Liposome Res., 2012, 22(2), 168-176.
[http://dx.doi.org/10.3109/08982104.2012.668552] [PMID: 22428938]
[28]
Langroodi, F.A.; Hafezi Ghahestani, Z.; Alibolandi, M.; Ebrahimian, M.; Hashemi, M. Evaluation of the effect of crocetin on antitumor activity of doxorubicin encapsulated in PLGA nanoparticles. Nanomed. J., 2016, 3(1), 23-34.