Uploaded by Tonmoye Sarkar

ZnP

advertisement
Synopsis of Research Project
Synthesis and Characterization of Biocompatible Polymer Modified Zn3(PO4)2 Nanoparticles for
Sustained Drug Delivery Vehicles
Introduction:
Zinc phosphate(ZnP) is nontoxic, slightly soluble in biological system[1] and have adorable
biocompatibility, since being a trace element, zinc is essential for a healthy immune system[2] whereas
phosphate, regarded as one of the body’s electrolytes, is present in cell membrane and even DNA[3]. Its
low solubility in blood indicates its long circulation time in bloodstream before excretion although there
is a contradictory statement that small-sized nanoparticles while having good penetration properties,
are cleared away rapidly[4]. Hence the nanoparticles are coated with hydrophilic polymer conjugated
with functional ligands or proteins ensuring long circulation and site-specific drug delivery[5]. Thus
formed organic/inorganic composite material would have combined advantages of both inorganic
materials (example: thermal stability) and organic polymer (example: flexibility, dielectric, ductility
and processablity)[6]. Once the surface of the nanoparticle is coated with polymer, it gets stabilized
either through steric stabilization or by depletion stabilization process[7] and the desired drugs are placed
in the vicinity of these polymeric molecules. The microenvironment of the tumor cells (in case of cancer
treatment), due to rapid proliferation, is slightly acidic at around pH 6.5 [8]. In order to enable controlled
drug release to the affected area, nanoparticles are further functionalized by pH-sensitive ligands. When
nanoparticles are accumulated there, these ligands get attached to the remaining solvent of the targeted
area and drugs get released. In this way, the pharmacokinetic profile, off-target and overall therapeutic
index of drugs can be altered using nanoparticles.
C. Wang et al. did an in vitro study of Fe3O4@C/ZnP nanoparticles for synergistic chemo-photothermal
cancer therapy[9]. For intestinal delivery of insulin, W. Paul and C.P. Sharma studied alginate coated
zinc calcium phosphate nanoparticles[10]. X.Yuan, B. Zhu et al. worked on hollow hydroxy zinc
phosphate nanospheres using anticancer doxorubicin as a model drug and found that they have high
drug loading capacity (>16 wt%) [11]. According to A.J. Jadav el al., the hollow structured zinc
phosphate nanoparticles synthesized by surfactant assisted sonochemical method, can be fruitfully
applied as nanocarrier[12].
In this research work, we will find out a biocompatible polymer from natural inexpensive sources (such
as psyllium seeds, shrimp) and functionalize it with ZnP nanoparticles. This will be further stuied to
investigate its chemical and physical properties including size, surface charge and surface chemistry in
order to determine the pharmacokinetics and biodistribution of the prepared nanoparticle for searching
out a sustained drug delivery vehicle.
Objectives:
The main aim of this thesis work are

Synthesize and characterize polymeric functionalized nanoparticles,
Investigating physiochemical behaviour of the prepared nanoparticles for pharmacokinetic
study and checking its ability as site-specific drug delivery agent.
Methodology:
The total procedure of this thesis work is divided into following stepsi.
Synthesis of Zn3(PO4)2 nanoparticles:
The ZP NPs will be prepared by solvothermal method.
ii.
Characterization of Zn3(PO4)2 nanoparticles:
The prepared nanoparticle will be characterised by using FT-IR, XRD, TEM and SEM analysis.
iii.
Functionalization of Zn3(PO4)2 nanoparticles by biocompatible hydrophilic polymer:
Sol gel method will be utilized for surface modification of Zn3(PO4)2 nanoparticles by a
polymer with interesting bio-mimetic character.
iv.
Characterization of polymer functionalized Zn3(PO4)2 nanoparticles:
The crystal structure, morphology and optical property of the prepared polymer functionalized
Zn3(PO4)2 nanoparticles will be investigated by XRD, SEM, TEM, FT-IR, Raman spectroscopy
and TGA.
v.
Pharmacokinetic study:
Surface charge, enhanced permeation, flexibility, solubility in biological system, kinetic study
in the bloodstream, compatibility with cytoplasm will be studied with a purpose of checking its
capability as a smart drug delivery vehicle.
Expected results:
1. The proposed synthesis method will produce polymer functionalized Zn3(PO4)2
nanoparticles.
2. The nanoparticles will show long-circulation property in bloodstream and highly
specific drug transport mechanism.
Time frame:
Period
October 2019- June 2020
Activity
Study of theoretical courses and planning of experimental program
for research project.
July 2020- August 2020
Theoretical examination of M.Sc.
September 2020- March 2021 Synthesize and characterize polymeric functionalized nanoparticles.
April 2021- June 2021
Investigating pharmacokinetic behaviour of prepared nanoparticles.
July 2021- September 2021
Preparation of thesis paper for publication.
Socio-economical importance:
Nanotechnology has received a lot of attention with the never-seen-before enthusiasm because of its
future potential that can literary revolutionize each field in which it is being exploited. Nanoparticles
can play a major role in medicine and especially in diagnosis and therapy of cancer cardiovascular and
infectious diseases. Conventional cancer treatment methods (example: surgery, chemotherapy,
radiation therapy, bone marrow transplant etc.) are still out of the reach of common people due to their
high out-of-pocket medical costs. Our prepared nanoparticle will be used in targeted drug therapy. We
will collect all our raw components from natural sources which have a huge abundance in market
indicating its cost effectiveness. Theoretically nanodrug can easily pass through the fine capillary blood
vessels and the lymphatic endothelium. Moreover, when equipped with bioadesive polymers or
chelators, this nanodrug will enhance both the transcellular and paracellular transport of the entrapped
drugs via the regulation of tight junctions without affecting other healthy cells. Additionally owing to
the effective pH response properties, ZnP nanoparticles can act selectively and with reduced side
effects. Thus it will contributor to the acceleration of pharmaceutical development.
Conclusion:
The desired polymer functionalized Zn3(PO4)2 nanoparticles will be prepared and characterized by
different analytical techniques for confirmation. This will be site-targeted, self-controlled and have
improved biocompatibility. These promising properties will be applied for facilitating cancer treatment
by selective targeting.
References:
1. A.J. Jadhav, C.R. Holkar, A.B. Pandit, D.V. Pinjari. Intensification of synthesis of crystalline zinc
phosphate nanopowder: advantage of sonochemical method over conventional method. Austin
Chem Eng. 3(2), 1028 (2016).
2. D.R. Wilson (2017). What are the health benefits of zinc? Retrieved from
http://www.medicalnewstoday.com/articles/263176
3. James L. Lewis, III (2018). Overview of phosphate’s role in body. Retrieved from
http://www.msdmauals.com/home/hormonal-and-metabollic-disorders/electrolutebalance/overview-of-phosphate-s-role-in-the-body
4. W. Yu, R. Liu, Y. Zhow and H.Gao. Size-tunable strategies for a tumor targeted drug delivery
system. ACS Central Science. 6(2), 100-116 (2020).
5. S.W. Chori, W.S. Kim, J.H. Kim. Surface modification of functional nanoparticles for controlled
drug delivery. J Dispersion Science and technology. 24, 475-487 (2013).
6. G. Markovic, P.M. Visakh. Recent developents in polymer macro, micro and nano blends.
Elsevier. 1-15 (2017).
7. D. Kopeliovich (2013). Stabilization of colloids. Retrieved from
http://www.subtech.com/dokuwiki/doku.php?id=stabilization of colloids
8. Engin K., Leeper D.B., Cuter J.R. et al. Extracellular pH distribution in human tumors.
International Journal of Hyperthermia. 11(2), 211-216 (1995).
9. C. Wang, L. Zhang, S. Li et al. A designed synthesis of multifunctional Fe3O4@C/ZnP
nanoparticles for simultaneous imaging and synergic chemophotothermal cancer therapy. Journal
of Materials Chemistry. B4(35), 5809-5813 (2016).
10. W. Paul, C.P. Sharma. Synthesis and characterization of alginate coated zinc calcium phosphate
nanoparticles for intestinal delivery of insulin. Process Biochemistry.47(5), 882-886 (2012).
11. X. Yuan, B. Zhu, X. Ma et al. Low temperature and template free synthesis of hollow hydroxy
zinc phosphate nanosphere in drug delivery. Langmuir. 29(39), 12275-12283 (2013).
12. A.J. Jadhav, D.V. Pinjari, A.B. Pandit. Surfactant assisted sonochemical synthesis of hollow
structured zinc phosphate nanoparticles and their application as nanocarrer. Chemical
Engineering Journal. 297, 116-120 (2016).
Signature of Applicant
Signature of Supervisor
Signature of Co-supervisor
Tonmoye Sarkar Shathi
M.Sc Student
Roll no: 1512023117
Department of Chemistry
Faculty of Scinece
University of Rajshahi
Rajshahi-6205, Bangladesh
Email: tonmoye.swati@gmail.com
Dr. Md. Rabiul Karim
Professor
Department of Chemistry
Faculty of Scinece
University of Rajshahi
Rajshahi-6205, Bangladesh
Mobile: +880 1714929969
Email: rabiul30@ru.ac.bd
Dr. Md. Abdur Rahman
Professor
Department of Chemistry
Faculty of Scinece
University of Rajshahi
Rajshahi-6205,Bangladesh
Mobile: +880 1728461363
Email: arahman@ru.ac.bd
Download