Synthesis and characterization of petox-dope liposome structure conjugated to peptide-18 for targeting breast cancer

Polyoxazolines are significant polymers with their biocompatibility as an alternative to polyehtylene glycol (PEG) in many biological and medical applications. This biocompatibility provides versatility to polymers in terms of their usage areas. Targeted drug delivery systems are one of these usage areas. It is possible to synthesize and design the polymer backbone of polyoxazolines in terms of proper molecular weights, desired end groups and functionalities. Poly(2-ethyl-2-oxazoline) is very prefered becasue of its high bio compatibility and similarity to PEG such as non-toxicity, solubility in water, mild reaction conditions in biomedical applications as a drug, gene or protein carrier. The versatile usage of Poly(2-ethyl-2-oxazoline) is increasing day by day against to increasing biological necessities of of polymers in medical researches and treatments. In this thesis study, the investigation of building liposome structure as a drug carrier system which is consisting of Poly(2-ethyl-2-oxazoline) as hydrophilic part and 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as lipophilic part. Poly(2-ethyl-2-oxazoline) was synthesized by using cationic ring opening polymerization technique. The initiator of the polymerization was also synthesized by designing in order to be obtained maleimide terminal polymer and the polymerization was terminated with sodium azide salt to be obtained also azide functional end polymer. In the synthesis route of the initiator, maleic anhydride and furan were reacted in toluene as a solvent, to produce furan protected maleimide. After that, ethanolamine was added and the product was undergone mesylation reaction by using mesyl chloride. The characterization of the initiator was provided by means of FTIR and NMR and results were presented step-by-step. The polymerization of 2-ethyl-2-oxazoline was successfully achieved by utilizing the initiator in proper amounts and reaction conditions in acetonitrile solvent. Then, the click reaction was carried out from the azide functional end of the polymer with 4-Pentynoic acid in the presence of copper sulfate and sodium ascorbate. After these modification of Poly(2-ethyl-2-oxazoline), the conjugation with DOPE was achieved via amidification reaction by using 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and triethylamine in reaction medium. Characterization studies of all these products were reported and listed all were proven with the results coming from FTIR and NMR spectrums. Targeting of liposome structure was carried out by binding specific peptide molecule, which is Peptide-18 for breast, and the observation of the targeted liposome was achieved by binding 7-Mercapto-4-methylcoumarin to the system. FTIR and NMR analysis were utilized to characterize these studies and results showed that the purpose of the study was actualized. This presented thesis study was supported by the project, numbered 213M725, titled as "Development of The Poly(2-ethyl-2-oxazoline) (PEtOx) Based Multifunctional Carrier Systems for Treatment and Diagnosis of The Prostate and The Breast Cancer" by TÜBİTAK.