Polymerization of D,L-lactide in the presence of Boltorn™ polyester polyol

Objects. To synthesize monodisperse biodegradable hyperbranched polymers based on D,L-lactide in the presence of Boltorn™ H30 polyester polyol as a macroinitiator.

Methods. 1H and 13C nuclear magnetic resonance (NMR) spectroscopy was used to study the chemical structure of the Boltorn™ H30 polyester polyol and (Boltorn™ H30)-PDLA hyperbranched copolymers. The molecular weight distribution of the polymers was studied by gel permeation chromatography (GPC). In order to study the thermal stability of Boltorn™ H30 polyester polyol, thermogravimetric analysis (TGA) was used. Polymerization of D,L-lactide was carried out in a block in the presence of Boltorn™ H30 polyester polyol.

Results. The degree of branching of Boltorn™ H30 polyester polyol was calculated from NMR data, while the TGA method was used to determine the upper operational temperature range. The polymerization of D,L-lactide in the presence of Boltorn™ H30 polyester polyol used as a macroinitiator was studied. The molecular weight characteristics of the obtained copolymers were studied by NMR and GPC.

Conclusions. Optimum conditions were determined for the polymerization of D,L-lactide when using Boltorn™ H30 polyester polyol as a macroinitiator. The possibility of synthesizing narrowly dispersed hyperbranched polymers (Boltorn™ H30)-PDLA under the described conditions was demonstrated.

1. Gelperina S.E., Shvets V.I. Drug Delivery Systems based on Polymeric Nanoparticles. Biotekhnologiya = Biotechnology in Russia. 2009;(3):1–21 (in Russ.).

2. Gomzyak V.I., Sedush N.G., Puchkov A.A., et al. Linear and Branched Lactide Polymers for Targeted Drug Delivery Systems. Polym. Sci. Ser. B. 2021;63(3):257–271. https://doi.org/10.1134/S1560090421030064 [Original Russian Text: Gomzyak V.I., Sedush N.G., Puchkov A.A., Polyakov D.K., Chvalun S.N. Linear and Branched Lactide Polymers for Targeted Drug Delivery Systems. Vysokomolekulyarnye soedineniya. Seriya B. 2021;63(3):190–206 (in Russ.). https://doi.org/10.31857/S2308113921030062 ]

3. Gomzyak V.I., Demina V.A., Razuvaeva E.V., Sedush N.G., Chvalun S.N. Biodegradable polymer materials for medical applications: from implants to organs. Fine Chemical Technologies. 2017;12(5):5–20 (in Russ.). https://doi.org/10.32362/2410-6593-2017-12-5-5-20

4. Agadzhanyan V.V., Pronskikh A.A., Demina V.A., Gomzyak V.I., Sedush N.G., Chvalun S.N. Biodegradable implants in orthopedics and traumatology. Our first experience. Politravma = Polytrauma. 2016;(4):85–93 (in Russ.)

5. Korake S., Shaikh A., Salve R., Gajbhiye K.R., Gajbhiye V., Pawar A. Biodegradable dendritic BoltornTM nanoconstructs: A promising avenue for cancer theranostics. Int. J. Pharm. 2021;594:120177. https://doi.org/10.1016/j.ijpharm.2020.120177

6. Gomzyak V.I., Puchkov A.A., Artamonova N.E., et al. Physico-chemical properties of biodegradable hyperbranched polyester polyol based on 2,2-bis(methylol) propionic acid. Fine Chemical Technologies. 2018;13(4):67–73 (in Russ.). https://doi.org/10.32362/2410-6593-2018-13-4-67-73

7. Zhang X., Dai Y., Dai G. Advances in amphiphilic hyperbranched copolymers with an aliphatic hyperbranched 2,2-bis(methylol)propionic acid-based polyester core. Polym. Chem. 2020;11(5):964–973. https://doi.org/10.1039/c9py01608b

8. Prabaharan M., Grailer J.J., Pilla S., et al. Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn H40, poly(l-lactide) and poly(ethylene glycol) for tumor-targeted drug delivery. Biomaterials. 2009;30(16):3009–3019. https://doi.org/10.1016/j.biomaterials.2009.02.011

9. Perše L.S., Huskić M. Rheological characterization of multiarm star copolymers. Eur. Polym. J. 2016;76:188–195. https://doi.org/10.1016/j.eurpolymj.2016.01.045

10. Hawker C.J., Lee R., Fréchet J.M.J. One-Step Synthesis of Hyperbranched Dendritic Polyesters. J. Am. Chem. Soc. 1991;113(12):4583–4588. https://doi.org/10.1021/ja00012a030

11. Žagar E., Žigon M. Characterization of a Commercial Hyperbranched Aliphatic Polyester Based on 2,2-Bis(methylol) propionic Acid. Macromolecules. 2002;35(27):9913–9925. https://doi.org/10.1021/ma021070o

12. Kricheldorf H.R., Kreiser-Saunders I., Boettcher C. Polylactones: 31. Sn(II)octoate-initiated polymerization of L-lactide: a mechanistic study. Polymer. 1995;36(6):1253–1259. https://doi.org/10.1016/0032-3861(95)93928-F

13. Kricheldorf H.R., Weidner S.M. High molar mass cyclic poly(L-lactide) obtained by means of neat tin(II) 2-ethylhexanoate. Polym. Chem.

14. Lecomte P., Jérôme C. Recent developments in ringopening polymerization of lactones. In: Rieger B., Künkel A., Coates G., Reichardt R., Dinjus E., Zevaco T. (Eds.). Synthetic Biodegradable Polymers. Advances in Polymer Science. 2012;245:173–218. https://doi.org/10.1007/12_2011_144

15. Tikhonov P.A., Vasilenko N.G., Muzafarov A.M. Multiarm Star Polymers. Fundamental Aspects. A Review. Doklady Chemistry. 2021;496(1):3–20. https://doi.org/10.1134/S001250082101002X

16. Perevyazko I., Seiwert J., Schömer M., Frey H., Schubert U.S., Pavlov G.M. Hyperbranched Poly(ethylene glycol) Copolymers: Absolute Values of the Molar Mass, Properties in Dilute Solution, and Hydrodynamic Homology. Macromolecules. 2015;48(16):5887–5898. https://doi.org/10.1021/acs.macromol.5b01020

17. Li H., Riva R., Kricheldorf H.R., Jérôme R., Lecomte P. Synthesis of eight- and star-shaped poly- (ε-caprolactone)s and their amphiphilic derivatives. Chemistry – A European Journal. 2008;14(1):358–368. https://doi.org/10.1002/chem.200700603

18. Massoumi B., Sarvari R., Agbolaghi S. Biodegradable and conductive hyperbranched terpolymers based on aliphatic polyester, poly(D,L-lactide), and polyaniline used as scaffold in tissue engineering. Int. J. Polym. Mater. 2018;67(13):808–821. https://doi.org/10.1080/00914037.2017.1383248

19. Michalski A., Brzezinski M., Lapienis G., Biela T. Star-shaped and branched polylactides: Synthesis, characterization, and properties. Prog. Polym. Sci. 2019;89:159–212. https://doi.org/10.1016/j.progpolymsci.2018.10.004

20. Tabatabaei Rezaei S.J., Abandansari H.S., Nabid M.R., Niknejad H. PH-responsive unimolecular micelles selfassembled from amphiphilic hyperbranched block copolymer for efficient intracellular release of poorly water-soluble anticancer drugs. J. Colloid Interface Sci. 2014;425:27–35. https://doi.org/10.1016/j.jcis.2014.03.034