Login Register Cart 0
Generic placeholder image

Cardiovascular & Hematological Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5257
ISSN (Online): 1875-6182

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Design and Development of Lomustine Loaded Chitosan Nanoparticles for Efficient Brain Targeting

Author(s): Anupriya Anand, Bharadhwaj Ramesh Iyer, Chandrasekar Ponnusamy, Rajesh Pandiyan and Abimanyu Sugumaran*

Volume 18, Issue 1, 2020

Page: [45 - 54] Pages: 10

DOI: 10.2174/1871525718666200203112502

Price: $65

Abstract

Aims: The present research work discussed the preparation of lomustine loaded with chitosan nanoparticles (LNCp) by ionic gelation method with homogenization using the design on experiments by Box-Behnken design.

Methods: The nanoparticles are evaluated by particle size, zeta potential, surface morphology, drug content, entrapment efficiency and in-vitro drug release.

Results: The FT-IR results support that drug have no interaction with excipients, which are used in the preparation of nanoparticle. The particle size, drug content and encapsulation efficiency of the developed nanoparticles ranged from 190 to 255 nm, 80.88% to 94.02%, and 77.12 to 88.74%, respectively. The drug release rate is diffusion-controlled over 8 hours. The F-value for all of the responses shows that the models are significant. The p-value, less than 0.05 for all the responses reveals the significance of the models. Graphical optimisation is done by desirability plot and overlay plot, which contains optimal values of independent variables with the desirability of 1.

Conclusion: In conclusion, the results suggested that the optimised lomustine loaded chitosan nanoparticles are useful for brain targeting hence hold the potential for further research and clinical application.

Keywords: Box-behnken design, brain targeting, chitosan nanoparticles, ionic gelation, lomustine, optimisation.

« Previous Next »
Graphical Abstract

[1]
Vogelstein, B.; Papadopoulos, N.; Velculescu, V.E.; Zhou, S.; Diaz, L.A., Jr; Kinzler, K.W. Cancer genome landscapes. Science, 2013, 339(6127), 1546-1558.
[http://dx.doi.org/10.1126/science.1235122] [PMID: 23539594]
[2]
Massagué, J.; Obenauf, A.C. Metastatic colonization by circulating tumour cells. Nature, 2016, 529(7586), 298-306.
[http://dx.doi.org/10.1038/nature17038] [PMID: 26791720]
[3]
Anand, A.; Sugumaran, A.; Narayanasamy, D. Brain targeted delivery of anticancer drugs: prospective approach using solid lipid nanoparticles. IET Nanobiotechnol., 2019, 13(4), 353-362.
[http://dx.doi.org/10.1049/iet-nbt.2018.5322] [PMID: 31171738]
[4]
Rahiminejad, A.; Dinarvand, R.; Johari, B.; Nodooshan, S.J.; Rashti, A.; Rismani, E.; Mahdaviani, P.; Saltanatpour, Z.; Rahiminejad, S.; Raigani, M.; Khosravani, M. Preparation and investigation of indirubin-loaded SLN nanoparticles and their anti-cancer effects on human glioblastoma U87MG cells. Cell Biol. Int., 2019, 43(1), 2-11.
[http://dx.doi.org/10.1002/cbin.11037] [PMID: 30080277]
[5]
Madan, J.; Pandey, R.S.; Jain, V.; Katare, O.P.; Chandra, R.; Katyal, A. Poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine improve biological half-life, brain delivery and efficacy in glioblastoma cells. Nanomedicine (Lond.), 2013, 9(4), 492-503.
[http://dx.doi.org/10.1016/j.nano.2012.10.003] [PMID: 23117045]
[6]
Elzoghby, A.O.; Abd-Elwakil, M.M.; Abd-Elsalam, K.; Elsayed, M.T.; Hashem, Y.; Mohamed, O. Natural polymeric nanoparticles for brain-targeting: Implications on drug and gene delivery. Curr. Pharm. Des., 2016, 22(22), 3305-3323.
[http://dx.doi.org/10.2174/1381612822666160204120829] [PMID: 26845323]
[7]
Tosi, G.; Bortot, B.; Ruozi, B.; Dolcetta, D.; Vandelli, M.A.; Forni, F.; Severini, G.M. Potential use of polymeric nanoparticles for drug delivery across the blood-brain barrier. Curr. Med. Chem., 2013, 20(17), 2212-2225.
[http://dx.doi.org/10.2174/0929867311320170006] [PMID: 23458620]
[8]
Liu, K.; Jiang, X.; Hunziker, P. Carbohydrate-based amphiphilic nano delivery systems for cancer therapy. Nanoscale, 2016, 8(36), 16091-16156.
[http://dx.doi.org/10.1039/C6NR04489A] [PMID: 27714108]
[9]
Raj, R.; Wairkar, S.; Sridhar, V.; Gaud, R. Pramipexole dihydrochloride loaded chitosan nanoparticles for nose to brain delivery: Development, characterization and in vivo anti-Parkinson activity. Int. J. Biol. Macromol., 2018, 109, 27-35.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.12.056] [PMID: 29247729]
[10]
Aderibigbe, B.A. In Situ-based gels for nose to brain delivery for the treatment of neurological diseases. Pharmaceutics, 2018, 10(2), 40.
[http://dx.doi.org/10.3390/pharmaceutics10020040] [PMID: 29601486]
[11]
Sarvaiya, J.; Agrawal, Y.K. Chitosan as a suitable nanocarrier material for anti-Alzheimer drug delivery. Int. J. Biol. Macromol., 2015, 72, 454-465.
[http://dx.doi.org/10.1016/j.ijbiomac.2014.08.052] [PMID: 25199867]
[12]
Nagpal, K.; Singh, S.K.; Mishra, D.N. Optimization of brain targeted chitosan nanoparticles of Rivastigmine for improved efficacy and safety. Int. J. Biol. Macromol., 2013, 59, 72-83.
[http://dx.doi.org/10.1016/j.ijbiomac.2013.04.024] [PMID: 23597710]
[13]
Naghibi Beidokhti, H.R.; Ghaffarzadegan, R.; Mirzakhanlouei, S.; Ghazizadeh, L.; Dorkoosh, F.A. Preparation, characterization, and optimization of folic acid-chitosan-methotrexate core-shell nanoparticles by box-behnken design for tumor-targeted drug delivery. AAPS PharmSciTech, 2017, 18(1), 115-129.
[http://dx.doi.org/10.1208/s12249-015-0445-3] [PMID: 26896317]
[14]
Brar, V.; Kaur, G. Preparation of chitosan okra nanoparticles: optimization and evaluation as mucoadhesive drug delivery system. Pharm. Nanotechnol., 2018, 6(3), 180-191.
[http://dx.doi.org/10.2174/2211738506666180813122437] [PMID: 30101724]
[15]
Fisusi, F.A.; Siew, A.; Chooi, K.W.; Okubanjo, O.; Garrett, N.; Lalatsa, K.; Serrano, D.; Summers, I.; Moger, J.; Stapleton, P.; Satchi-Fainaro, R.; Schätzlein, A.G.; Uchegbu, I.F. Lomustine nanoparticles enable both bone marrow sparing and high brain drug levels - a strategy for brain cancer treatments. Pharm. Res., 2016, 33(5), 1289-1303.
[http://dx.doi.org/10.1007/s11095-016-1872-x] [PMID: 26903051]
[16]
Jojo, G.M.; Kuppusamy, G.; De, A.; Karri, V.V.S.N.R. Formulation and optimization of intranasal nanolipid carriers of pioglitazone for the repurposing in Alzheimer’s disease using Box-Behnken design. Drug Dev. Ind. Pharm., 2019, 45(7), 1061-1072.
[http://dx.doi.org/10.1080/03639045.2019.1593439] [PMID: 30922126]
[17]
Parhi, R.; Suresh, P.; Patnaik, S. Application of response surface methodology for design and optimization of reservoir-type transdermal patch of simvastatin. Curr. Drug Deliv., 2016, 13(5), 742-753.
[http://dx.doi.org/10.2174/1567201812666151009115944] [PMID: 26452533]
[18]
Zhu, S.; Hong, M.; Liu, C.; Pei, Y. Application of Box-Behnken design in understanding the quality of genistein self-nanoemulsified drug delivery systems and optimizing its formulation. Pharm. Dev. Technol., 2009, 14(6), 642-649.
[http://dx.doi.org/10.3109/10837450902882385] [PMID: 19883253]
[19]
Natesan, S.; Sugumaran, A.; Ponnusamy, C.; Thiagarajan, V.; Palanichamy, R.; Kandasamy, R. Chitosan stabilized camptothecin nanoemulsions: Development, evaluation and biodistribution in preclinical breast cancer animal mode. Int. J. Biol. Macromol., 2017, 104(Pt B), 1846-1852.
[20]
Sugumaran, A.; Ponnusamy, C.; Kandasamy, P.; Krishnaswami, V.; Palanichamy, R.; Kandasamy, R.; Lakshmanan, M.; Natesan, S. Development and evaluation of camptothecin loaded polymer stabilized nanoemulsion: Targeting potential in 4T1-breast tumour xenograft model. Eur. J. Pharm. Sci., 2018, 116, 15-25.
[http://dx.doi.org/10.1016/j.ejps.2017.10.005] [PMID: 28987538]
[21]
Mehrotra, A.; Nagarwal, R.C.; Pandit, J.K. Lomustine loaded chitosan nanoparticles: characterization and in-vitro cytotoxicity on human lung cancer cell line L132. Chem. Pharm. Bull. (Tokyo), 2011, 59(3), 315-320.
[http://dx.doi.org/10.1248/cpb.59.315] [PMID: 21372411]
[22]
Mehrotra, A.; Nagarwal, R.C.; Pandit, J.K. Fabrication of lomustine loaded chitosan nanoparticles by spray drying and in vitro cytostatic activity on human lung cancer cell line L132. J. Nanomed. Nanotechnol., 2010, 1, 103.
[http://dx.doi.org/10.4172/2157-7439.1000103]
[23]
Agarwal, S.; Jangir, D.K.; Singh, P.; Mehrotra, R. Spectroscopic analysis of the interaction of lomustine with calf thymus DNA. J. Photochem. Photobiol. B, 2014, 130, 281-286.
[http://dx.doi.org/10.1016/j.jphotobiol.2013.11.017] [PMID: 24368412]
[24]
Mehrotra, A.; Pandit, J.K. Preparation and characterization and biodistribution studies of lomustine loaded PLGA nanoparticles by interfacial deposition method. J. Nanomed. Nanotechnol., 2015, 6, 6.
[http://dx.doi.org/10.4172/2157-7439.1000328]
[25]
Ahmed, T.A.; Aljaeid, B.M. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery. Drug Des. Devel. Ther., 2016, 10, 483-507.
[http://dx.doi.org/10.2147/DDDT.S99651] [PMID: 26869768]
[26]
Patel, K.S.; Patel, M.B. Preparation and evaluation of chitosan microspheres containing nicorandil. Int. J. Pharm. Investig., 2014, 4(1), 32-37.
[http://dx.doi.org/10.4103/2230-973X.127738] [PMID: 24678460]
[27]
Jain, A.; Thakur, K.; Sharma, G.; Kush, P.; Jain, U.K. Fabrication, characterization and cytotoxicity studies of ionically cross-linked docetaxel loaded chitosan nanoparticles. Carbohydr. Polym., 2016, 137, 65-74.
[http://dx.doi.org/10.1016/j.carbpol.2015.10.012] [PMID: 26686106]
[28]
Joseph, J.J.; Sangeetha, D.; Gomathi, T. Sunitinib loaded chitosan nanoparticles formulation and its evaluation. Int. J. Biol. Macromol., 2016, 82, 952-958.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.10.079] [PMID: 26522243]
[29]
Saini, S.; Kumar, S.; Choudhary, M. Nitesh; Budhwar, V. Chitosan loaded microspheres of tropicamide as controlled release of drug for ocular drug delivery system. Int. Res. J. Pharm., 2017, 8(11), 95-102.
[http://dx.doi.org/10.7897/2230-8407.0811225]
[30]
Rasyid, N.Q.; Sugita, P.; Ambarsari, L.; Syahbirin, G. Suspension stability and characterization of chitosan nanoparticle-coated ketoprofen based on surfactants oleic acid and poloxamer 188. Makara J. Sci., 2014, 18, 86-90.

Rights & Permissions Print Cite
Article Metrics
32
2
© 2024 Bentham Science Publishers | Privacy Policy