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