syed zaigham abbas kazmi ph.d biochemistry 08-arid-1112
TRANSCRIPT
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Beta-casein and its complexes with chitosan as nanovehicles for delivery of a platinum
anticancer drug Syed Zaigham Abbas Kazmi
Ph.D Biochemistry08-arid-1112
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Nanotechnology
Design, Synthesis and application of the materials and devices whose size and shape have been engineered at the nanoscale
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NanoparticleParticles atleast one dimension smaller than one micron and potentially as small as atomic and molecular length scales
They may be• Amorphous
or• Crystalline
Act as carrier for liquid droplet or gases and can include metal atoms and large molecules such as proteins
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Nanoparticles and tumor targetingNanomedicines have enormous potential to improve the precision of cancer
therapy
They have the ability to encapsulate the therapeutic drug and target them to
the tumor cells.
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Platinum based anticancer drugsThese are the co-ordinate complexes of platinum
Examples include Cis platin Carboplatin Triplatin
Platinum complexes cause cross linking of the DNA which inhibits the DNA repair and synthesis
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Beta Casein and Chitosan as nanovehicle for the drug delivery
A new drug delivery system comprising a novel platinum complex (bipyridine morpho-line dithiocarbamate Pt(II) nitrate) within nanoparticles composed of Beta-casein and chitosan.
The influence of pH on the formation of a colloidally-stable nanocarrier system composed of Pt complex-loaded Beta-CN and chitosan nanoparticles was investigated using
UV–vis spectrometry
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Dynamic light scattering (DLS) scanning electron microscopy (SEM)
There is considerable interest in the use of natural biopolymers, such as proteins and polysaccharides, to build particular delivery systems
Nanoparticle formation of proteins and carbohydrates based on the principle of attractive and repulsive forces
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Beta-Casein• one of the most abundant proteins in bovine milk and having the
properties of
Self organization Micelles formation
• Beta-CN micelles may be efficient as drug vehicles targeting neo-plastic cells.
• Recent reports suggest that Beta-CN nanoparticles can be used for the entrapment and oral delivery of anti-neoplastic agents
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one of the problems of using Beta-CN nanoparticles as potential nanocarriers is that drug molecules may interact with their surfaces
So, keeping in view this problem, Chitosan has been used as a secondary coating for the controlled and targeted release of the drug
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ChitosanA cationic polysacchride with increasing number of pharmaceutical and
biomedical applications
Beneficial biological properties include Biocompatibility Biodegradibility Non toxicity Low immunogenecity
• chitosan can interact with proteins especially with whole casein forming either soluble or insoluble complexes depending on the pH
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Prepration of platinum complex and its 2 mM stock soln in
distilled water
Prepration of 0.5mg/ml stock soln of Beta casein in 0.1 M
sodium phosphate buffer
Prepration of 0.05% w/v in 0.01% acetate buffer
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Pt complex and Beta casein solution in 3:1
Addition of Chitosan stock soln to drug-Beta casein soln
Titartion to achieve the desired pH
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DLS and Zeta potential studyThe average size and size distribution of the drug-loaded NPs were
determined using DLS/zeta potential analysis
Particle size distribution was studied by DLS at 25◦C using 0.89 cp for the viscosity of the medium, a fixed angle 90◦for the avalanche photo diode (APD) detector and the wavelength of 678 nm for the 90 mW laser
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The zeta potential of nanoparticles was measured using a zeta potential analyzer at 25◦C
The samples were diluted with distilled water and placed in the electrophoretic cell for zeta potential measurements
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Scanning electron microscopy (SEM)
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pH Mean diameter (Polydispersity) Zeta potential (mV)
3 – Drug aggregation –
5.7 250 ± 5 0.11 ± 0.01 +30 ± 0.6
6.2 270 ± 4 0.17 ± 0.01 +29 ± 1
7 – Precipitation –
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CytotoxicityThe cytotoxicity of the drug was studied by using MTT assay
The human colon tumor cell line (HCT-116) was selected to assay the in vitro cytotoxicity of the new synthesized Pt(II) complex, either free or encapsulated in CS– Beta-CN micelles
Optical density of both treated and control cells were taken and the cell viability was calculated by the formula
Cell viability (%) =Atreated/Acontrol × 100
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ConclusionNanoparticles consist of CS-Beta-casein loaded with bypyridine
morpholine dithiocarbomate are potentially useful as a vehicle for cancer therapy
Nanocomplex were stable and soluble at pH 5.7 and 6.2 according to SEM, DLS and Zeta potential analysis
Drug efficacy of the Platinum complex was improved by encapsulating in NPs
This newly designed nanocarrier could be a promising candidate for clinical trials for the treatment of different carcinomas
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References M.Razmi,. A. Divsalar., A.A. sabouri., Z. izadi ., T. Hertle and H. mansuri.2013. Beta-casein and its
complexes with chitosan as nanovehicles for the delivery of platinum anticancer drug. Colloids and surfaces: Biointerfaces. 112: 362-367
M. Geofrey., P. Ji-Ho., L. kevin Y., S. Nitu., S. Christian and M. Rolf. 2011. Nanoparticles that communicate invivo to amplify tumor targeting. Nature materials.
E. Wrong and M. Giandimanico . 1999. Current status of platinum based anticancer drugs. Chem. 99: 2451-2466
J. Rieter., M. Pott., M. L. Taylor and L. Weinbin. Nanoscale Coordination Polymers for Platinum-Based Anticancer Drug Delivery. 2008. JACS. 130: 11584-11585
S. Gangnard, Y. Zuev, J. Gaudin, V. Fedotov, Y. Choiset, M.A.V. Axelos, J. Chobert,T. Haertlé, Modifications of the charges at the N-terminus of bovine -casein:consequences on its structure and its micellisation, Food Hydrocol. 21 (2007)180–190
J. Gaudin, A.L. Parc, B. Castrec, M. Ropers, Y. Choiset, J. Shchutskaya, R. Yousefi,V.I. Muronetz, Y. Zuev, J. Chobert, T. Haertlé, Engineering of caseins and modula-tion of their structures and interactions, Biotechnol. Adv. 27 (2009) 1124–1131.
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“If anyone travels on a road in search of knowledge, Allah will cause him to travel on one of the roads of Paradise”.
(HAZRAT MUHAMMAD S.A.W)