• Roxana Maria JELERIU Victor Babes” University of Medicine and Pharmacy Timisoara
  • Lidia Manuela ONOFREI “Victor Babes” University of Medicine and Pharmacy Timisoara
  • F. BORCAN “Victor Babes” University of Medicine and Pharmacy Timisoara
  • Ramona Carmen ALBUILESCU “Victor Babes” University of Medicine and Pharmacy Timisoara
  • Maria PUIU “Victor Babes” University of Medicine and Pharmacy Timisoara


2’-Deoxycytidylic acid, a nucleotide based on cytosine, deoxyribose and phosphate group, is a fundamental unit of nucleic acids. Various supplements containing nucleosides or nucleotides have been formulated for patients with genetic defects resulting in the presence of incorrect nucleotides. The aims of the current research were to obtain and to characterize polyurethane transporters that can be used for the transfer of nucleotides through body membranes. Materials and methods: Three samples have been developed based on different synthesis temperatures and the effects of this parameters on the properties of the final products were assessed; there were measured the solubility, pH, refractivity index, the encapsulation efficacy and release profile, size distribution and surface charge, cells proliferation and irritation tests on mice skin. Results: The obtained mean values show that were obtained almost neutral acido-basic particles with sizes range from 126 to 814 nm; Zeta potential values indicate the tendency to form clusters in samples with synthesis temperatures above 40°C, while UV-Vis evaluations show an approx. 60% encapsulation efficacy. Regarding the biosafety profile of the samples, the assays on cells culture and mice skin did not elicit important side effects at tested concentration. Conclusions: The findings of this preclinical study suggest that polyurethane carriers exhibit promise as a therapeutic or preventative measure for a range of diseases by addressing genetic irregularities, demonstrating their safety for such applications.

Author Biographies

Roxana Maria JELERIU, Victor Babes” University of Medicine and Pharmacy Timisoara

Faculty of Medicine
Ph.D. School

Lidia Manuela ONOFREI, “Victor Babes” University of Medicine and Pharmacy Timisoara

Faculty of Medicine
Ph.D. School

F. BORCAN, “Victor Babes” University of Medicine and Pharmacy Timisoara

Faculty of Pharmacy
Department I (Advanced Instrumental Screening Center)

Ramona Carmen ALBUILESCU, “Victor Babes” University of Medicine and Pharmacy Timisoara

Faculty of Medicine
Department XI (Pediatrics II)

Maria PUIU, “Victor Babes” University of Medicine and Pharmacy Timisoara

Faculty of Medicine
Department II (Microscopic Morphology)
Regional Center of Medical Genetics


1. Marks AR. DNA: The Secret of Life. J Clin Invest 2003; 112(7): 972 / doi:10.1172/JCI20020.
2. Moffatt BA, Ashihara H. Purine and pyrimidine nucleotide synthesis and metabolism. Arabidopsis Book 2002; 1: e0018. / doi:10.1199/tab.0018.
3. Boison D. Adenosine and epilepsy: from therapeutic rationale to new therapeutic strategies. Neuro-scientist 2005; 11(1): 25-36 / doi:10.1177/1073858404269112
4. Moretto MB, Boff B, Lavinsky D, et al. Importance of schedule of administration in the therapeutic efficacy of guanosine: early intervention after injury enhances glutamate uptake in model of hypoxia-ischemia. J Mol Neurosci 2009; 38(2): 216-219 / doi: 10.1007/s12031-008-9154-7.
5. Zamzow CR, Bose R, Parkinson FE. N-methyl-D-aspartate-evoked adenosine and inosine release from neurons requires extracellular calcium. Can J Physiol Pharmacol 2009; 87(10): 850-858 / doi: 10.1139/Y09-075.
6. Cansev M. Uridine and cytidine in the brain: their transport and utilization. Brain Res Rev 2006; 52(2): 389-397 / doi: 10.1016/j.brainresrev.2006.05.001.
7. Boison D. Modulators of nucleoside metabolism in the therapy of brain diseases. Curr Top Med Chem 2011; 11(8): 1068-1086 / doi:10.2174/156802611795347609.
8. Preusch PC. Chapter 14. Equilibrative and Concentrative Transport Mechanisms. In: Principles of Clinical Pharmacology (Atkinson AJ, Abernethy DR, Daniels CE, Dedrick RL, Markey SP, editors.), Academic Press, 2007; 197-227.
9. Joseph TM, Kar Mahapatra D, Esmaeili A, et al. Nanoparticles: Taking a Unique Position in Medicine. Nanomaterials (Basel) 2023; 13(3): 574. / doi:10.3390/nano13030574
10. Bouchemal K, Briançon S, Perrier E, Fessi H, Bonnet I, Zydowicz N. Synthesis and characterization of polyurethane and poly(ether urethane) nanocapsules using a new technique of interfacial polycon-densation combined to spontaneous emulsification. Int J Pharm 2004; 269(1): 89-100 / doi: 10.1016/ j.ijpharm.2003.09.025.
11. Bouchemal K, Briançon S, Perrier E, Fessi H. Nano-emulsion formulation using spontaneous emulsi-fication: solvent, oil and surfactant optimisation. Int J Pharm 2004; 280(1-2): 241-251 / doi: 10.1016 /j.ijpharm.2004.05.016.
12. Bouchemal K, Briançon S, Couenne F, Fessi H, Tayakout M. Stability studies on colloidal suspensions of polyurethane nanocapsules. J Nanosci Nanotechnol 2006; 6(9-10): 3187-3192 / doi:10.1166 /jnn.2006.468.
13. Borcan F, Chirita-Emandi A, Andreescu NI, et al. Synthesis and preliminary characterization of polyurethane nanoparticles with ginger extract as a possible cardiovascular protector. Int J Nanomed 2019; 14: 3691-3703 / doi:10.2147/IJN.S202049.
14. Munteanu MF, Ardelean A, Borcan F, et al. Mistletoe and Garlic Extracts as Polyurethane Carriers – A Possible Remedy for Choroidal Melanoma. Curr Drug Deliv 2017; 14(8): 1178-1188/ doi:10.2174/ 1567201814666170126113231.
15. Tuta-Sas I, Borcan F, Sas I. Synthesis and preliminary characterization of polyurethane matrices used as a drug carrier for bromelain. Mater Plast 2023; 60(1): 1-12.
16. Fiorio R, Pistor V, Zattera AJ, Petzhold CL. Influence of synthesis temperature on thermal properties of thermoplastic polyurethane prepared by torque rheometer. Polym Eng Sci 2012; 52: 1678-1684 / doi:10.1002/pen.23117.
17. Citu C, Ceuta L, Popovici R, Ionescu D, Pinzaru I, Borcan F. Alternative Possibilities to Asses a Phytohormone Release Rate from a Polyurethane Carrier. Mater Plast 2015; 52(4): 553-559.
18. Moleriu L, Duse AO, Borcan F, et al. Formulation and characterization of anti-bacterial hydrogels based on polyurethane microstructures and 1,2,4-triazole derivatives. Mater Plast 2017; 54(2): 348-352.
19. Baino F, Yamaguchi S. The Use of Simulated Body Fluid (SBF) for Assessing Materials Bioactivity in the Context of Tissue Engineering: Review and Challenges. Biomimetics (Basel) 2020; 5(4): 57 / doi:10.3390/biomimetics5040057.
20. Silva RRA, Marques CS, Arruda TR, Teixeira SC, de Oliveira TV. Biodegradation of Polymers: Stages, Measurement, Standards and Prospects. Macromol 2023; 3: 371-399. / doi: 10.3390/ macro-mol3020023.
21. Begines B, Ortiz T, Pérez-Aranda M, et al. Polymeric Nano-particles for Drug Delivery: Recent Developments and Future Prospects. Nanomaterials (Basel) 2020; 10(7): 1403. / doi: 10.3390/ nano10071403.
22. Elmowafy M, Shalaby K, Elkomy MH, et al. Polymeric Nanoparticles for Delivery of Natural Bioac-tive Agents: Recent Advances and Challenges. Polymers 2023; 15: 1123. / doi: 10.3390/ polym15051123.
23. Batyrbekov Y, Iskakov R. Polyurethane as Carriers of Antituberculosis Drugs. In: Polyurethane (Zafar F, Sharmin E, eds.) IntechOpen, Rijeka, Croatia, 2012. / doi:10.5772/35896
24. Laidler KJ. Chemical Kinetics, Third Edition, Harper & Row, 1987.
25. Zhang Z, Brgoch J. Treating Superhard Materials as Anomalies. J Am Chem Soc 2022; 144(39): 18075-18080 / doi:10.1021/jacs.2c07957.
26. Kabantseva VE, Safonov MD, Plokhikh AI. Study of thermal expansion anomalies of multilayer steel materials at high temperatures. IOP Conf Ser: Mater Sci Eng 2018; 683: 012047.
27. Zhang T, Evans JRG. Anomalies in the thermal expansion of ceramic, injection moulded bodies. J Mater Sci Lett 1990; 9: 672-674. / doi:10.1007/BF00721799.
28. Andreev AV. Chapter 2 Thermal expansion anomalies and spontaneous magnetostriction in rare-earth intermetallics with cobalt and iron. Handbook of Magnetic Materials, Elsevier, 1995; 8: 59-187 / doi:10.1016/S1567-2719(05)80031-9.
29. Castillo GE, Thompson BC. Room Temperature Synthesis of a Well-Defined Conjugated Polymer Using Direct Arylation Polymerization (DArP). ACS Macro Lett 2023; 12(10): 1339-1344 / doi:10.1021/acsmacrolett.3c00396.
30. Thermal Polymerization (Internet). Available from: materials-science/thermal-polymerization (Last accessed on December 6, 2023).
31. Takasu A, Makino T, Yamada S. Polyester Synthesis at Moderate Temperatures via the Direct Poly-condensation of Dicarboxylic Acids and Diols Catalyzed by Rare-Earth Perfluoro-alkanesulfonates and Bis(perfluoroalkanesulfonyl)imides. Macromolecules 2010; 43(1): 144-149/ doi:10.1021/ma04 75378.
32. Benyahya S, Boutevin B, Caillol S, Lapinte V, Habas JP. Optimization of the synthesis of polyhy-droxyurethanes using dynamic rheometry. Polym int 2012; 61: 918-925. / doi: 10.1002/ pi.4159.
33. Zhansitov A, Kurdanova Z, Shakhmurzova K, Slonov A, Borisov I, Khashirova S. Effect of Solvent and Monomer Ratio on the Properties of Polyphenylene Sulphone. Polymers 2023; 15: 2279. / doi:10.3390/polym15102279.
34. Mouren A, Avérous L. Sustainable cycloaliphatic polyurethanes: from synthesis to applications. Chem Soc Rev 2023; 52: 277-317. / doi:10.1039/D2CS00509C
35. Iwazumi M, Schneider A. High refractive index aqueous polyurethane dispersion coating compositions. WO2011163461A1, 2011.
36. Tekade AR, Yadav JN. A Review on Solid Dispersion and Carriers Used Therein for Solubility En-hancement of Poorly Water-soluble Drugs. Adv Pharm Bull 2020; 10(3): 359-369 / doi: 10.34172 /apb.2020.044.
37. Batyrbekov Y, Iskakov R. Polyurethane as Carriers of Antituberculosis Drugs. In: Polyurethane; Zafar F, Sharmin E, Eds.; IntechOpen, Rijeka, Croatia, 2012 / doi:10.5772/35896
38. Oprean C, Borcan F, Pavel I, et al. In Vivo Biological Evaluation of Polyurethane Nano-structures with Ursolic and Oleanolic Acids on Chemically-induced Skin Carcinogenesis. In Vivo 2016; 30(5): 633-638.
39. Gurita (Ciobotaru) VG, Pavel IZ, Borcan F, et al. Toxicological Evaluation of Some Essential Oils Obtained from Selected Romania Lamiaceae Species in Complex with Hydroxypropyl - gammacy-clodextrin. Rev Chim Bucharest 2019; 70(10): 3703-3707.