POLYETHYLENE GLYCOL-CHITOSAN NANOPARTICLE GEL FOR THE CONTROLLED NASAL DELIVERY OF NOSCAPINE AGAINST GLIOMA

Authors

  • NOOPUR DIXIT Department of Pharmaceutical Chemistry, SOP, CEC, Bilaspur, India https://orcid.org/0000-0001-8131-5917
  • ADITYA TRIVEDI Department of Pharmaceutical Chemistry, SIP, Bilaspur India https://orcid.org/0000-0001-8131-5917
  • DHEERAJ AHIRWAR Department of Pharmaceutical Chemistry, SOP, CEC, Bilaspur, India

DOI:

https://doi.org/10.22159/ijap.2022v14i3.43779

Keywords:

Glioma, Intranasal delivery, Nanoparticle gel, In vitro, Blood-brain barrier

Abstract

Objective: To synthesize the PEG surface modulated Chitosan Nanoparticles aiding in Pluronic intranasal gel (PEG-CHT-PL) encapsulating cytotoxic noscapine for enhanced anticancer effect against glioma.

Methods: The PEG-CHT-PL was synthesized by inotropic gelation method and evaluated for in vitro characterization parameters such as zeta sizer, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), zeta potential followed by gelling time, Thixotropy and flow index evaluation. The cell uptake assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) evaluation and apoptosis was evaluated on human Glioblastoma U-87 cell line post evaluation by evaluating drug release pattern at 7.4 pH by PBS buffer for stable intranasal brain delivery.

Results: The synthesized PEG-CHT-PL showed nanosize range of 110 nm and a smooth spherical shape with a negative zeta potential of27±1.9 mV. The gel showed stable rheology exhibiting negligible normal deviation in viscosity, Thixotropy and flow index on long-term storage. The drug release pattern followed the Higuchi’s model in 48 h at 7.4pH showed sustained noscapine discharge. The in vitro Glioblastoma U-87 cell line studies showed enhanced cell uptake and distribution, with notable cell toxicity by MTT and apoptosis evaluation confirming significant antitumor efficiency via intranasal delivery.

Conclusion: The present research has showed promising operational intranasal therapy against brain tumor crossing BBB efficiently and can be subjected for an effective antitumor approach in clinical platform in future drug delivery system.

Downloads

Download data is not yet available.

References

Nagpal K, Singh SK, Mishra DN. Evaluation of safety and efficacy of brain targeted chitosan nanoparticles of minocycline. Int J Biol Macromol. 2013;59:20-8. doi: 10.1016/j.ijbiomac.2013.04.011, PMID 23587996.

Wilson B, Samanta MK, Muthu MS, Vinothapooshan G. Design and evaluation of chitosan nanoparticles as novel drug carrier for the delivery of rivastigmine to treat Alzheimer’s disease. Ther Deliv. 2011;2(5):599-609. doi: 10.4155/tde.11.21, PMID 22833977.

Sarvaiya J, Agrawal YK. Chitosan as a suitable nanocarrier material for anti-Alzheimer drug delivery. Int J Biol Macromol. 2015;72:454-65. doi: 10.1016/j.ijbiomac.2014.08.052, PMID 25199867.

Bowman K, Leong KW. Chitosan nanoparticles for oral drug and gene delivery. Int J Nanomedicine. 2006;1(2):117-28. doi: 10.2147/nano.2006.1.2.117, PMID 17722528.

Nikai T, Basbaum AI, Ahn AH. Profound reduction of somatic and visceral pain in mice by intrathecal administration of the anti-migraine drug, sumatriptan. Pain. 2008;139(3):533-40. doi: 10.1016/j.pain.2008.06.002, PMID 18723285.

Bartsch T, Knight YE, Goadsby PJ. Activation of 5-HT (1B/1D) receptor in the periaqueductal gray inhibits nociception. Ann Neurol. 2004;56(3):371-81. doi: 10.1002/ana.20193, PMID 15349864.

Okamoto K, Thompson R, Tashiro A, Chang Z, Bereiter DA. Bright light produces Fos-positive neurons in caudal trigeminal brainstem. Neuroscience. 2009;160(4):858-64. doi: 10.1016/j.neuroscience.2009.03.003, PMID 19285114.

Vijayan L, Bansal D, Ray SB. Nimodipine down-regulates CGRP expression in the rat trigeminal nucleus caudalis. Indian J Exp Biol. 2012;50(5):320-4. PMID 22803321.

Landen JW, Hau V, Wang M, Davis T, Ciliax B, Wainer BH, Van Meir EG, Glass JD, Joshi HC, Archer DR. Noscapine crosses the blood–brain barrier and inhibits glioblastoma growth. Clin Cancer Res. 2004;10(15):5187-201. doi: 10.1158/1078-0432.CCR-04-0360, PMID 15297423.

Aneja R, Dhiman N, Idnani J, Awasthi A, Arora SK. Preclinical pharmacokinetics and bioavailability of noscapine, a tubulinbinding anticancer agent. Cancer Chemotherpharmacol. 2007;60:831-9.

Gibaldi M, Weiner ND. Biphasic elimination of noscapine. J Pharm Sci. 1966;55(8):769-71. doi: 10.1002/jps.2600550804, PMID 5975287.

Madan J, Dhiman N, Parmar VK, Sardana S, Bharatam PV, Aneja R, Chandra R, Katyal A. Inclusion complexes of noscapine in β-cyclodextrin offer better solubility and improved pharmacokinetics. Cancer Chemother Pharmacol. 2010;65(3):537-48. doi: 10.1007/s00280-009-1060-3, PMID 19597818.

Elisabetta G, Hegge AB, Rassu G, Sanna V, Testa C, Pirisino G, Karlsen J, Giunchedi P. Nasal administration of carbamazepine using chitosan microspheres: in vitro/in vivo studies. J Pharm Sci. 2006;307:9-15.

Arora P, Sharma S, Garg S. Permeability issues in nasal drug delivery. Drug Discov Today. 2002;7(18):967-75. doi: 10.1016/s1359-6446(02)02452-2, PMID 12546871.

Bahadur S, Pathak K. Physicochemical and physiological considerations for efficient nose-to-brain targeting. Expert Opin Drug Deliv. 2012;9(1):19-31. doi: 10.1517/ 17425247.2012.636801, PMID 22171740.

Rapoport AM, Bigal ME, Tepper SJ, Sheftell FD. Intranasal medications for the treatment of migraine and cluster headache. CNS Drugs. 2004;18(10):671-85. doi: 10.2165/00023210-200418100-00004, PMID 15270595.

Ricci EJ, Lunardi LO, Nanclares DMA, Marchetti JM. Sustained release of lidocaine from poloxamer 407 gels. Int J Pharm. 2005;288(2):235-44. doi: 10.1016/j.ijpharm.2004.09.028, PMID 15620863.

Guideline, ICH harmonised tripartite. Stability testing of new drug substances and products. Current Step 4. 2003;431-2: (p. R2).

Lin Z, Parsons DL, Navarre C, Kompella UB. Development and in vitro evaluation of sustained release poloxamer 407. J Control Release. 2002;85:73-81.

Schmolka IR. Artificial skin. I. Preparation and properties of pluronic F-127 gels for treatment of burns. J Biomed Mater Res. 1972;6(6):571-82. doi: 10.1002/jbm.820060609, PMID 4642986.

Bhandwalkar MJ, Avachat AM. Thermoreversible nasal in situ gel of venlafaxine hydrochloride: formulation, characterization, and pharmacodynamic evaluation. AAPS PharmSciTech. 2013;14(1):101-10. doi: 10.1208/s12249-012-9893-1, PMID 23229381.

Kumar A, Garg T, Sarma GS, Rath G, Goyal AK. Optimization of combinational intranasal drug delivery system for the management of migraine by using statistical design. Eur J Pharm Sci. 2015;70:140-51. doi: 10.1016/j.ejps.2015.01.012, PMID 25676136.

Majithiya RJ, Ghosh PK, Umrethia ML, Murthy RSR. Thermoreversible-mucoadhesive gel for nasal delivery of sumatriptan. AAPS PharmSciTech. 2006;7(3):67. doi: 10.1208/pt070367, PMID 17025248.

Bakliwal SR, Pawar SP. In situ gel: new trends in controlled and sustained drug delivery system. Int J PharmTech Res. 2010;2:1398-408.

Cho HJ, Balakrishnan P, Park EK, Song KW, Hong SS, Jang TY, Kim KS, Chung SJ, Shim CK, Kim DD. Poloxamer/cyclodextrin/chitosan‐based thermoreversible gel for intranasal delivery of fexofenadine hydrochloride. J Pharm Sci. 2011;100(2):681-91. doi: 10.1002/jps.22314, PMID 20803575.

Kempwade A, Taranalli A. Formulation and evaluation of thermoreversible, mucoadhesive in situ intranasal gel of rizatriptan benzoate. J Sol–Gel Sci. 2014;72:43-8.

Bunjes H, Westesen K, Koch MHJ. Crystallization tendency and polymorphic transitions in triglyceride nanoparticles. International Journal of Pharmaceutics. 1996;129(1-2):159-73. doi: 10.1016/0378-5173(95)04286-5.

Hou D, Xie C, Huang Kand Zhu CHuang K, Zhu C. The production and characteristics of solid lipid nanoparticles (SLNs). Biomaterials 2003;24(10):1781-5. doi: 10.1016/s0142-9612(02)00578-1, PMID 12593960.

Helgason T, Awad TS, Kristbergsson K, McClements DJ, Weiss J. Effect of surfactant surface coverage on formation of solid lipid nanoparticles (SLN). Journal of Colloid and Interface Science 2009;334(1):75-81. doi: 10.1016/j.jcis.2009.03.012, PMID 19380149.

Dhuria SV, Hanson LR, Frey WH. Intranasal drug targeting of hypocretin-1 (orexin-A) to the central nervous system (orexin‐A) to the central nervous system. Journal of Pharmaceutical Sciences. 2009;98(7):2501-15. doi: 10.1002/jps.21604, PMID 19025760.

Rahman Z, Zidan AS, Khan MA. Non-destructive methods of characterization of risperidone solid lipid nanoparticles. European Journal of Pharmaceutics and Biopharmaceutics. 2010;76(1):127-37. doi: 10.1016/j.ejpb.2010.05.003, PMID 20470882.

Chen F, Zhang ZR, Yuan F, Qin X, Wang M, Huang Y. In vitro and in vivo study of N-trimethyl chitosan nanoparticles for oral protein delivery. International Journal of Pharmaceutics. 2008;349(1-2):226-33. doi: 10.1016/j.ijpharm.2007.07.035, PMID 17825506.

Wang Y, Cui J, Sun X, Zhang Y. Tunneling-nanotube development in astrocytes depends on p53 activation. Cell Death and Differentiation. 2011;18(4):732-42. doi: 10.1038/cdd.2010. 147, PMID 21113142.

Tosi G, Vilella A, Chhabra R, Schmeisser MJ, Boeckers TM, Ruozi B, Vandelli MA, Forni F, Zoli M, Grabrucker AM. Insight on the fate of CNS-targeted nanoparticles. Part II: Intercellular neuronal cell-to-cell transport. Journal of Controlled Release 2014;177:96-107. doi: 10.1016/j.jconrel.2014.01.004, PMID 24417968.

Newcomb EW, Lukyanov Y, Smirnova I, Schnee T, Zagzag D. Noscapine induces apoptosis in human glioma cells by an apoptosis-inducing factor-dependent pathway. Anticancer Drugs. 2008;19(6):553-63. doi: 10.1097/CAD.0b013e3282ffd68d. PMID 18525314.

Sharma S, Lohan S, Murthy RSR. Formulation and characterization of intranasal mucoadhesivenanoparticulates and thermo-reversible gel of levodopa for brain delivery. Drug Dev Ind Pharm. 2014;40(7):1-10869-78. doi: 10.3109/03639045.2013.789051, PMID 23600649.

Raikar PR, M Dandagi P. Functionalized polymeric nanoparticles: A novel targeted approach for oncology care. Int J App Pharm. 2021;13(6):1-18. doi: 10.22159/ ijap.2021v13i6.42714.

Published

07-05-2022

How to Cite

DIXIT, N., TRIVEDI, A., & AHIRWAR, D. (2022). POLYETHYLENE GLYCOL-CHITOSAN NANOPARTICLE GEL FOR THE CONTROLLED NASAL DELIVERY OF NOSCAPINE AGAINST GLIOMA. International Journal of Applied Pharmaceutics, 14(3), 153–161. https://doi.org/10.22159/ijap.2022v14i3.43779

Issue

Section

Original Article(s)