2023 (4) 7

https://doi.org/10.15407/polymerj.45.04.319

FILM-FORMING COMPOSITIONS BASED ON POLYURETHANEUREAS WITH EXTENDED RELEASE OF DACARBAZINE

S.O. Prymushko,
Institute of Macromolecular Chemistry NAS of Ukraine, 48, Kharkivske Shose, Kyiv, 02155, Ukraine,
e-mail: nork345@gmail.com
ORCID: 0000-0002-3623-1068

N.A. Galatenko,
Institute of Macromolecular Chemistry NAS of Ukraine, 48, Kharkivske Shose, Kyiv, 02155, Ukraine,
e-mail: galatenkonataliia@gmail.com
ORCID: 0000-0002-5961-5750

R.A. Rozhnova,
Institute of Macromolecular Chemistry NAS of Ukraine, 48, Kharkivske Shose, Kyiv, 02155, Ukraine,
e-mail: rozhnovarita@gmail.com
ORCID: 0000-0003-3284-3435

G.A. Kozlova,
Institute of Macromolecular Chemistry NAS of Ukraine, 48, Kharkivske Shose, Kyiv, 02155, Ukraine,
e-mail: politoks@merlin.net.ua
ORCID: 0000-0001-8114-4812

I.I. Gladyr,
Institute of Macromolecular Chemistry NAS of Ukraine, 48, Kharkivske Shose, Kyiv, 02155, Ukraine,
e-mail: politoks@merlin.net.ua
ORCID: 0000-0002-6248-2709

L.Yu. Nechaeva,
Institute of Macromolecular Chemistry NAS of Ukraine, 48, Kharkivske Shose, Kyiv, 02155, Ukraine,
e-mail: l.ne4aeva@gmail.cоm
ORCID: 0000-0003-1716-2105

Polym. J., 2023, 45, no. 4: 319-327.

Section: Medical polymers.

Language: Ukrainian.

Abstract:

Composite materials with dacarbazine (DK) containing 1 wt. % were obtained on the basis of polyurethane ureas (PUU) containing in the structure as extenders of the macrochain of 2-(2-aminoethoxy)ethan-1-amine, (DA1) 3,6-dioxaoctane-1,8-diamine (DA2) 3-{2-[2-(3-aminopropoxy)ethoxy]ethoxy}propan-1-amine (DA3) with a molar ratio of 4,4’-diaminodiphenylmethane (DADPh) to DA1 and DA3 as 30:70; 50:50; 70:30. The tensile strength of the compositions is within (1.21-1.27) MPa, the relative elongation is (303.9-384)%. Studies of thermophysical properties of synthesized PUU by DSC, TGA methods were conducted. Dacarbazine compositions are single-phase systems with glass transition temperature (Tg) from -33.55°C to -37.06°C. It was established that the introduction of Dacarbazine into the composition of PUU leads to a decrease in Tg and ΔCp during the second warm-up in comparison with the original PUU. Dacarbazine compositions are resistant to temperatures of 270oC, which allows for thermal sterilization before use. The release of Dacarbazine from polymer samples into the solution was studied by the spectrophotometric method. According to the results of the study of the dynamics release of Dacarbazine, it was es tablished that for (PUU DA1)2+DK in 14 days it is 61.74%, (PUU DA2)4+DK – 70.09%, (PUU DA3)2+DK – 56.75% of the total amount of immobilized DK. The resulting composites are perspective materials for medicine as means of local prolonged therapeutic action.

Keywords: polyurethaneurea, diamines, dacarbazine, prolonged release.

REFERENCES

1. Yanchao W, Ruichao L, Jingjing L, Jinlin C, Qiao Z, Jiehua L, et al. Biodegradable polyurethane nerve guide conduits with different moduli influence axon regeneration in transected peripheral nerve injury. Journal of materials chemistry. B, 2021, 9(38): 7979-7990. https://doi.org/10.1039/d1tb01236c.
2. Galatenko N.A., Rozhnova R.A., Astapenko O.O., Malanchuk V.O. Biolohichno aktyvni poliuretanovi kompozytsii dlia kistkovo plastychnykh operatsii lytsevoho skeleta Polimernyi zhurnal, 2023, 45, No. 1: 15-26. https://doi.org/10.15407/polymerj.45.01.015.
3. Zia K.M, Anjum S., Zuber M., Mujahid M., Jamil T., Synthesis and molecular characterization of chitosan based polyurethane elastomers using aromatic diisocyanate, Int. J. Biol. Macromol. 2014, 66: 26–32 https://doi.org/10.1016/j.ijbiomac.2014.01.073.
4. Teo A.J.T., Mishra A., Park I., Kim Y.-J., Park W.-T., Yoon Y.-J., Polymeric biomaterials for medical implants and devices, ACS Biomater. Sci. Eng. 2016, 2 (4): 454–472, https://doi.org/10.1021/acsbiomaterials.5b00429.
5. Vislohuzova T, Rozhnova R, Galatenko N, Narazhayko L, Rudenko A. Study of biodegradation, biocompatibility and bactericidal activity of film materials with tiamulin fumarate based on polyurethane urea. Chemistry & Chemical Technology, 2020, 14(3): 318-326 https://doi.org/10.23939/chcht14.03.318.
6. Sivak W.N., Zhang J., Petoud S., Beckman E.J., Simultaneous drug release at different rates from biodegradable polyurethane foams, Acta Biomater. 2009, 5: 2398–2408. https://doi.org/10.1016/j.actbio.2009.03.036.
7. Wang A., Gao H., Sun Y., Sun Y-l., Yang Y.-W., Wang G. Wu, Y., Fan Y., Ma J., Temperature and pH-responsive nanoparticles of biocompatible polyurethanes for doxorubicin delivery, Int. J. Pharm. 2013, 441: 30–39. https://doi.org/10.1016/j.ijpharm.2012.12.021.
8. Brown, K.V.; Wenke, J.C.; Guelcher, S.A. Sustained release of vancomycin from polyurethane scaffoldsinhibits infection of bone wounds in a rat femoral segmental defect model. J. Control. Release 2010, 145: 221–230. https://doi.org/10.1016/j.jconrel.2010.04.002.
9. Shoaib, Muhammad, et al. Sustained drug delivery of doxorubicin as a function of pH, releasing media, and NCO contents in polyurethane urea elastomers. Journal of Drug Delivery Science and Technology 2017, 39: 277-282. https://doi.org/10.1016/j.jddst.2017.04.010.
10. Basak, P.; Adhikari, B.; Banerjee, I.; Maiti, T.K. Sustained release of antibiotic from polyurethane coated implant materials. J. Mater. Sci. Mater. Med. 2009, 20: 213–221. https://doi.org/10.1007/s10856-008-3521-3.
11. Moura, S.A.L.; Lima, L.D.C.; Andrade, S.P.; Silva-Cunha Junior, A. Da; Órefice, R.L.; Ayres, E.; Da Silva, G.R. Local Drug Delivery System: Inhibition of Inflammatory Angiogenesis in a Murine Sponge Model by Dexamethasone-Loaded Polyurethane Implants. J. Pharm. Sci. 2011, 100: 2886–2895. https://doi.org/10.1002/jps.22497
12. K.M. Zia, S. Anjum, M. Zuber, M. Mujahid, T. Jamil, Synthesis and molecular characterization of chitosan based polyurethane elastomers using aromatic diisocyanate, Int. J. Biol. Macromol. 2014, 66: 26–32, https://doi.org/10.1016/j.ijbiomac.2014.01.073.
13. Galatenko N. A., Rozhnova R.A., Kuliesh D. V., Denisenko V. D., Maletskyy A. P., Bigun N. M. Rat tissue responses to dacarbazine-containing implants made of cross-linked polyurethane of different densities., Journal of Ophthalmology (Ukraine), 2022, (507) No 4: 40-48, http://doi.org/10.31288/oftalmolzh202244048.
14. Denysenko V.D., Galatenko N.A., Rozhnova R.A., Nechaieva L.Iu. Izotsianuratvmisni pinopoliuretansechovyny, napovneni dakarbazynom, dlia medytsyny Materialy II Mizhnarodnoi naukovoi konferentsii «Teoretychni ta eksperymentalni aspekty suchasnoi khimii ta materialiv TASKh-2023», 20 travnia 2023r., m. Dnipro: 48–51.
15. Prymushko S, Galatenko N, Rozhnova R, Kozlova G, Gladyr I. Synthesis and research of new polyurethane ureas that contain 1,8-diamino-3,6-dioxooctane as extender of macrochain. Polymer Journal. 2022, 44, No 3: 231-238, https://doi.org/10.15407/polymerj.44.03.231.
16. Prymushko S.O., Kozlova H.A., Hladyr I.I., Rozhnova R.A., Galatenko N.A. Syntez ta vlastyvosti novykh poliuretansechovyn medychnoho pryznachennia, yaki mistiat yak podovzhuvachi diaminy z atomamy oksyhenu v lantsiuzi Mizhnarodna naukova konferentsiia «Teoretychni ta eksperymentalni aspekty suchasnoi khimii ta materialiv TASKh-2022» Dnipro, Ukraina, 20 travnia 2022: 29–32.