Biocompatible and thermoresponsive polymer synthesis: A facile method for a controlled polymerization

Introduction: Stimuli responsive copolymers derived from oligo (ethylene glycol) methacrylate are promising biocompatible materials that present thermoresponsive properties which make them suitable as injectable drug... [ view full abstract ]

Introduction:
Stimuli responsive copolymers derived from oligo (ethylene glycol) methacrylate are promising biocompatible materials that present thermoresponsive properties which make them suitable as injectable drug delivery systems. These polymers are soluble in water, and undergo a transition to water-insoluble materials over a certain temperature called lower critical solution temperature (LCST). This temperature can be tuned by changing the oligo (ethylene glycol) methyl ether methacrylate (OEGMA) to di (ethylene glycol) methyl ether methacrylate (MEO2MA) monomer ratios [1]. The development of efficient and facile strategies for the synthesis of well-defined polymer architectures is a significant challenge necessary to overcome. Most usual Cu-mediated radical polymerizations present some drawbacks like high sensitivity of the catalyst to oxygen and water, and the requirement of exhaustive polymer purification processes to remove traces of the potentially toxic metal. In the present work, P(MEO2MA-co-OEGMA500) copolymers were prepared through three different synthetic methods with high reproducibility and narrow molecular weight distributions.
Methods:
Thermoresponsive P(MEO2MA-co-OEGMA500) was obtained via a photochemical controlled ATRP-like polymerization and compared with the common methods of synthesis including atom transfer radical polymerization (ATRP) and atom transfer radical polymerization with activators generated by electron transfer (AGET-ATRP). The ATRP and AGET-ATRP methods use organic complexes derived from copper as catalysts. Conversely, the photopolymerization employs a photocatalyst activated upon UV light irradiation. The polymers obtained were characterized by NMR spectroscopy, cloud point measurement, FTIR, GPC and TGA.
Results and Discussion:
It was possible to obtain thermoresponsive P(MEO2MA-co-OEGMA500) by photopolymerization, ATRP and AGET-ATRP methods. The LCST of the copolymer was adjusted to the physiological temperature range by changing the OEGMA/MEO2MA monomers molar ratio to be used in biomedical applications. The results showed low-polydispersity and control over the molecular weight and polymer composition under the three methods of synthesis. However, the photocatalized reaction has several advantages compared to the others. By following this method it is possible to produce a reversible activation and deactivation of the polymerization upon UV light irradiation. Moreover, it is a user-friendly method with simple reaction conditions which allows the use of reduced amounts of catalyst.
[1] J.F. Lutz, A. Hoth, Macromolecules 2006, 39, 893.