Syed Zaigham Abbas Kazmi
Ph.D Biochemistry
08-arid-1112
Nanotechnology
 Design, Synthesis and application of the materials and devices whose size
and shape have been engineered at the nanoscale
Nanoparticle
Particles 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
Nanoparticles and tumor targeting
 Nanomedicines 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.
Platinum based anticancer drugs
 These 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
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
 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
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
 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
Chitosan
 A 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
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
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
DLS and Zeta potential study
 The 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
 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
Scanning electron microscopy (SEM)
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
–
Cytotoxicity
 The 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
Conclusion
 Nanoparticles 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
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.
“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)