Chondroitin Sulphate Decorated Polymeric Nanoparticles: An Effective Carrier for Enhancement of Lung Cancer Targeting Capabilities of Anticancer Drug

Author(s): Sweta Garg, Ashish Garg, Sreenivas Enaganti, Awesh K. Yadav*

Journal Name: Current Nanomedicine
Formerly Recent Patents on Nanomedicine

Volume 9 , Issue 3 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Currently, cancer is rising as one of the dominant causes of human deaths worldwide. The application of nano-carriers may help to treat cancer through the delivery of anticancer drugs inside the tumor cells.

Objective: The foremost objective behind this research was to formulate chondroitin sulfate tailored cellulose acetate phthalate (CSAC) core shield nanoparticles (NPs) containing 5-Fluorouracil (5-FU) as an anticancer drug.

Methods: The FTIR and 1H-NMR spectroscopic methods were used to analyze and characterize the formulation of CSAC copolymer. NPs were typified by Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), Atomic Force Microscopy (AFM), Entrapment efficiency and in-vitro drug release.

Results: CSAC NPs were found to exhibit moderate release (95.59±0.15% in 34hrs) than CAP NPs (78.97±0.08% in 8 hours). In the course of cytotoxicity examination in A549 cancer cell line, the results revealed that these 5-FU loaded CSAC NPs showed an immense cytotoxic potentiality. Moreover, CSAC NPs exhibit least hemolytic activity when compared with CAP NPs and plain 5-FU.

Conclusion: Conclusively, it was found that the CSAC NPs is an efficient carrier system for the better release of 5-FU in lung cancer.

Keywords: Nanoparticles, 5-fluorouracil, cellular cytotoxicity, chondroitin sulfate, cellulose acetate phthalate, lung cancer.

[1]
Nagahara LA, Lee JS, Molnar LK, et al. Strategic workshops on cancer nanotechnology. Cancer Res 2010; 70: 4265-8.
[2]
Misra R, Acharya S, Sahoo SK. Cancer nanotechnology: application of nanotechnology in cancer therapy. Drug Discov Today 2010; 15: 842-50.
[3]
Parveen S, Sahoo SK. Polymeric nanoparticles for cancer therapy. J Drug Target 2008; 16: 108-23.
[4]
Wang X, Yang L, Chen ZG, et al. Application of nanotechnology in cancer therapy and imaging. Cancer J Clin 2008; 58: 97-110.
[5]
Maeda H, Wu J, Sawa T, et al. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 2000; 65: 271-84.
[6]
Kaul G, Amiji M. Long-circulating poly (ethylene glycol)-modified gelatin nanoparticles for intracellular delivery. Pharm Res 2002; 19: 1061-7.
[7]
Mikami KT, Uyama T, Mizuguchi S, et al. Recent advances in the structural biology of chondroitin sulfate and dermatan sulfate. Curr Opin Struct Biol 2003; 13: 612-20.
[8]
Chaturvedi K, Tripathi SK, Kulkarni AR, et al. Cytotoxicity and antitumour activity of 5- fluorouracil-loaded polyhydroxybutyrate and cellulose acetate phthalate blend microspheres. J Microencapsul 2013; 30: 356-68.
[9]
Neurath AR, Strick N, Li YY, et al. Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120. BMC Infect Dis 2001; 1: 17.
[10]
Spitael J, Kinget R, Naessens K. Dissolution rate of cellulose acetate phthalate and bronsted catalysis law. Die Pharmazeutische Industrie 1980; 42: 846-9.
[11]
Shapiro WR, Green SB, Burger PC, et al. A randomized comparison of intra-arterial versus intravenous with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma. J Neurosurg 1992; 76: 772-81.
[12]
Hutchins SJ, Green PM, Ravdin Lew D, et al. Randomized controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102. J Clin Oncol 2005; 23: 8313-21.
[13]
Longley DB, Harkin DP, Johnston PG. 5-Fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 2003; 3: 330-8.
[14]
Parker WB, Cheng YC. Metabolism and mechanism of action of 5-fluorouracil. Pharmacol Ther 1990; 48: 381-95.
[15]
Beck P, Scherer D, Kreuter J. Separation of drug-loaded nanoparticles from free drug by gel filtration. J Microencapsul 1990; 7(4): 491-6.
[16]
Casale F, Canaparo R, Muntoni E, et al. Simultaneous HPLC determination of 5-fluorouracil and its metabolites in plasma of cancer patients. Biomed Chromatogr 2002; 16: 446-52.
[17]
Ciccolini J, Mercier C, Blachon MF, et al. A simple and rapid high-performance liquid chromatographic (HPLC) method for 5-fluorouracil (5-FU) assay in plasma and possible detection of patients with impaired dihydropyrimidine dehydrogenase (DPD) activity. J Clin Pharm Ther 2004; 29: 307-15.
[18]
Compagnon P, Thiberville L, Moore N, et al. Simple high-performance liquid chromatographic method for the quantitation of 5-fluorouracil in human plasma. J Chromatogr B 1996; 677: 380-3.
[19]
Garg A, Rai G, Lodhi S, et al. In-vitro and in-vivo assessment of dextran-appended cellulose acetate phthalate nanoparticles for transdermal delivery of 5-fluorouracil. Drug Deliv 2014; 24: 1-11.
[20]
Muthu MS, Feng S. Pharmaceutical stability aspects of nanomedicines. Nanomed 2009; 4: 857-60.
[21]
International Conference on Harmonization, ICH Q1A (R2), Stability Testing Guidelines: Stability Testing of New Drug Substances and Products ICH step 5, CPMP/ICH/2736/99, London;. 2003.
[22]
Skehan P, Storeng R, Scudiero D, et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 1990; 82(13): 1107-12.
[23]
Wilson AP. In: Masters JRW, Eds.. Cytotoxicity and viability assays.Animal Cell Culture. Oxford University Press, New York 2000; pp. 175-219.
[24]
Tian Q, Streuli M, Saito H, et al. Apolyadenylate binding protein localized to the granules of cytolytic lymphocytes induces DNA fragmentation in target cells. Cell 1991; 67: 629-39.
[25]
Hwang HJ, Kang YJ, Hossain MA, et al. Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces apoptosis and cell cycle arrest in HCT116 human colon cancer cell. Int J Oncol 2012; 41(6): 2057-64.
[26]
Polakovic M, Gorner T, Gref R, et al. Lidocaine loaded biodegradable nanospheres. II. Modelling of drug release. J Control Release 1999; 60(2-3): 169-77.
[27]
Awotwe-Otoo D, Zidan AS, Rahman Z, et al. Evaluation of anticancer drug-loaded nanoparticles characteristics by nondestructive methodologies. AAPS PharmSciTech 2012; 13(2): 611-22.
[28]
Yadav AK, Mishra P, Jain S, et al. Preparation and characterization of HA-PEG-PCL intelligent core-corona nanoparticles for delivery of doxorubicin. J Drug Target 2008; 6: 464-78.
[29]
Hu Z, Xia X, Tang L. Process for synthesizing oil and surfactant-free hyaluronic acid nanoparticles and microparticles. US Patent 7601704B2 2009.
[30]
Yadav AK, Agarwal A, Jain S, et al. Chondroitin sulphate decorated nanoparticulate carriers of 5-fluorouracil: development and in vitro characterization. J Biomed Nanotechnol 2010; 6: 1-11.
[31]
Garg A, Patel V, Sharma R, et al. Heparin-appended polycaprolactone core/corona nanoparticles for site specific delivery of 5-fluorouracil. Artif Cells Nanomed Biotechnol 2016; 4: 1-10.
[32]
Garg A, Rai G, Lodhi S, et al. Hyaluronic acid embedded cellulose acetate phthlate core/shell nanoparticulate carrier of 5-fluorouracil. Int J Biol Macromol 2016; 87: 449-59.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 9
ISSUE: 3
Year: 2019
Page: [243 - 261]
Pages: 19
DOI: 10.2174/2468187309666190126112933
Price: $65

Article Metrics

PDF: 26
HTML: 2
EPUB: 1
PRC: 1