PREPARATION AND CHARACTERIZATION OF GEMCITABINE LOADED MPEG-PCL POLYMERIC NANOPARTICLES FOR IMPROVED TRANSPORTATION ACROSS BLOOD BRAIN BARRIER

Authors

  • B. V. Nagarjuna Yadav Vels University
  • V. Ravichandiran Vels University
  • S. Sathesh Kumar Department of Pharmaceutics, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Vels University, Chennai 600117, Tamilnadu, India

Keywords:

Cancer, Apoptosis, Gemcitabine, Glial cells, MPEG-PCL, Nanoparticles, Modified nanoprecipitation method

Abstract

Objective: To prepare Gemcitabine (GCB) loaded Methoxy Polyethylene Glycol-Poly (Caprolactone), (MPEG-PCL) nanoformulations and to carry out the physicochemical characterisation with a primary objective to enhance the transport and penetration of drug across the blood-brain barrier (BBB).

Methods: Gemcitabine loaded MPEG-PCL nanoparticles were formulated by using modified nanoprecipitation method. Nanoformulations were prepared by varying drug: polymer ratio. The prepared nanoparticles (NP) were evaluated for particle size, zeta potential, entrapment efficiency, drug content and in-vitro drug release studies. The in vitro cytotoxicity of drug-loaded NPs was evaluated in U-87 MG cells.

Results: The prepared nanoformulations indicated a significant increase in particle size with increase in the polymeric concentration. GCB loaded MPEG-PCL nanoformulation (GCBNP 3) exhibited a particle size of 223±1.4 nm. DSC thermo grams indicated that GCB was dispersed as an amorphous state in MPEG NPs. SEM, TEM, and AFM studies indicated that the NPs were spherical, smooth surface without any cracks or pinholes. In vitro studies showed the GCBNP 3 shows an initial burst release followed by a more gradual and sustained-release phase (maximum drug release). The cytotoxicity of GCB loaded MPEG-PCL nanoformulations showed reduction in the IC50 value (4.1 µg). Apoptosis detection assay with Hoechst 33342 dye was carried out and observed an increase in fluorescence in the apoptotic cells. By invasive studies, the GCB loaded MPEG-PCL nanoformulation inhibits the cell migration significantly when compared with the pure drug.

Conclusion: The GCB loaded MPEG-PCL nano particles indicated improved cytotoxic activity with minimal concentrations compared with the pure drug in U-87 MG glial cells. Hence, it can be concluded that GCB loaded MPEG-PCL nanoformulation can serve as a potential drug delivery tool for the treatment of brain tumours.

 

Downloads

Download data is not yet available.

References

Imran Ali, Waseem A, Wani, Kishwar Saleem. Cancer scenario in india with future perspectives. Cancer Ther 2011;8:56-70.

Balkrishna B Yeole. Trends in the brain cancer incidence in india. Asian Pacific J Cancer Prev 2008;9:267-70.

M Intakhab Alam, Sarwar Beg, Abdus Samad, Sanjula Baboota, Kanchan Kohli, Javed Ali, et al. Strategy for effective brain drug delivery. Eur J Pharm Sci 2010;40:385-403.

Mi Kyung Yu, Jinho Park, Sangyong Jon. Targeting strategies for multifunctional nanoparticles in cancer imaging and therapy. Theranostics 2012;2:3-44.

K Michaelis, MM Hoffmann, S Dreis, E Herbert, RN Alyautdin, M Michaelis, et al. Covalent linkage of apolipoprotein e to albumin nanoparticles strongly enhances drug transport into the brain. J Pharmacol Exp Ther 2006;317:1246-53.

RN Aliautdin, J Kreuter, DA Kharkevich. Drug delivery to the brain with nanoparticles. Eksp Klin Farmakol 2003;66:65-8.

J Kreuter. Nanoparticulate systems for brain delivery of drugs. Adv Drug Delivery Rev 2001;47:65-81.

WM Pardridge. Intravenous non-viral RNAi gene therapy of brain cancer. Expert Opin Biol Ther 2004;4:1103-13.

Y Zhang, WM Pardridge. Delivery of beta-galactosidase to mouse brain via the blood–brain barrier transferrin receptor. J Pharmacol Exp Ther 2005;313:1075-81.

Dimple Chopra, Monica Gulati, Vikrant Saluja, Purnima Pathak, Parikshit Bansal. Brain permeable nanoparticles, recent patents on CNS. Drug Discovery 2008;3:216-25.

Avgoustakis K. Pegylated poly (lactide) and poly (lactide–co–glycolide) nanoparticles, preparation, properties and possible application in drug delivery. Curr Drug Delivery 2004;1:321–33.

K Bhaskar Reddy, V Vaijayanthi, S Brito Raj, E Mohanambal, R Charulatha, Y Madhusudan Rao. Nanoparticles for brain targeting. Indian J Novel Drug Delivery 2011;3:91-7.

Viacheslav Chubenko, Aleksandr Nikolaevich Stukov, Olesya Belyaeva, Vladimir Bespalov, Fedor Vladimirovich Moiseenko, Valentina Lukyanchikova, et al. Therapeutic effect of gemcitabine on experimental tumors of the brain. J Clin Oncol 2013;31:e13005.

J Sigmond, RJ Honeywell, TJ Postma, CMF Driven, SM de Lange, K van der Born, et al. Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer. Ann Oncol 2009; 20:182-7.

Reddy LH, Couvreur P. Novel approaches to deliver Gemcitabine to cancers. Curr Pharm Des 2008;14:1124-37.

Joshi SA, Chavhan SS, Sawant KK. Rivastigmine loaded PLGA and PBCA nanoparticles: preparation, optimization, Characterization, in vitro and pharmacodynamic studies. Eur J Pharm Biopharm 2010;76:189-99.

Archana Mehrotra, Jayanta K Pandit. Critical process parameters evaluation of modified nanoprecipitation method on lomustine nanoparticles and cytostatic activity study on L132 human cancer cell line. J Nanomedic Nanotechnol 2012;3:1-8.

K Elkharraz, N Faisant, C Gusec, F Siepmann, B Arica-Yegin, JM Oger, et al. Paclitaxel-loaded microparticles and implants for the treatment of brain cancer: Preparation and physicochemical characterization. Int J Pharm 2006;314:127-36.

Yanna Cui, Qingxing Xu, Pierce Kah-Hoe Chow, Deping Wang, Chi-Hwa Wang. Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment. Biomaterials 2013;34:8511-20.

Bhavna, Shadab Md, Mushir Ali, Sanjula Baboota, Jasjeet Kaur Sahni, Aseem Bhatnaga, et al. Preparation, characterization, in vivo biodistribution and pharmacokinetic studies of donepezil-loaded PLGA nanoparticles for brain targeting. Drug Dev Ind Pharm 2014;40:278-87.

Eerikainen H, Kauppine EI. Preparation of polymeric nanoparticles containing corticosteroid by a novel aerosol flow reactor method. Int J Pharm 2003;263:69-83.

Mohanraj VJ, Chen Y. Nanoparticles: a review. Trop J Pharm Res 2006;5:561-73.

Fernandez CA, Baumhover NJ, Duskey JT, Khargharia S, Kizzire K, Ericson MD. Metabolically stabilized long-circulating PEGylated poly acridine peptide polyplexes mediate hydrodynamically stimulated gene expression in liver. Gene Ther 2011;18:23-37.

Calvo P, Gouritin B, Villarroya H, Eclancher F, Giannavola C, Klein C, et al. Quantification and localization of PEGylated poly cyanoacrylate nanoparticles in the brain and spinal cord during experimental allergic encephalomyelitis in the rat. Eur J Neurosci 2002;15:1317-26.

Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM. Polymeric systems for controlled drug release. Chem Rev 1999;99:3181-98.

Nair LS, Laurencin CT. Biodegradable polymers as biomaterials. Prog Polym Sci 2007;32:762-98.

Chang SM, Kuhn JG, Robins HI, Schold SC, Spence AM, Berger MS, et al. D, A phase II study of paclitaxel in patients with recurrent malignant glioma using different doses depending upon the concomitant use of anticonvulsants: a North American brain tumor consortium report. Cancer 2001;91:417-22.

Alyautdin RN, Petrov VE, Langer K, Berthold A, Kharkevich DA, Kreuter J. Delivery of loperamide across the blood–brain barrier with polysorbate 80-coated poly butyl cyanoacrylate nanoparticles. Pharm Res 1997;14:325–8.

Barichello JM, Morishita M, Takayama K, Nagai T. Encapsulation of hydrophilic and lipophilic drugs in PLGA nanoparticles by the nanoprecipitation method. Drug Dev Ind Pharm 1999;25:471-6.

Vandana M, Sahoo SK. Optimization of physicochemical parameters influencing the fabrication of protein-loaded chitosan nanoparticles. Nanomed 2009;4:773-85.

Published

01-01-2016

How to Cite

Yadav, B. V. N., V. Ravichandiran, and S. S. Kumar. “PREPARATION AND CHARACTERIZATION OF GEMCITABINE LOADED MPEG-PCL POLYMERIC NANOPARTICLES FOR IMPROVED TRANSPORTATION ACROSS BLOOD BRAIN BARRIER”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 1, Jan. 2016, pp. 83-90, https://journals.innovareacademics.in/index.php/ijpps/article/view/8211.

Issue

Section

Original Article(s)