(333c) Influence of Composition and Reaction Conditions on the Static and Dynamic Properties of Biodegradable Poly(curcumin beta amino ester) Networks

For the past 30+ years, hydrogels have garnered a lot of attention due to their applications in drug delivery, tissue engineering and regenerative medicine. Hydrogels are typically biocompatible, owing to their high water absorption capacity and the ability to tailor mechanical properties to achieve biomimetic performance. Biodegradable hydrogels are advantageous for biomedical applications as the hydrogel can degrade and be removed from the body once its function is achieved. A one-step hydrogel synthesis method was recently developed enabling preparation of biodegradable poly(antioxidant β amino ester) hydrogels for antioxidant delivery without the use of free radical chemistry [1]. Poly(antioxidant β amino esters) synthesized using this method improve the delivery of antioxidants that display limited aqueous solubility and environmental instability. The drug of interest in this work is curcumin, which has been shown to possess antioxidant, anti-inflammatory, anti-cancer and anti-angiogenesis properties. In this study, we explore a series of poly(curcumin β amino ester) PCbAE hydrogels formed by polymerization of commercial diacrylate (PEGDA) and a primary diamine in combination with acrylate-functionalized curcumin (i.e., curcumin diacrylate or CDA). PCbAE undergoes hydrolytic degradation to release curcumin in its original form. The network properties of these gels were characterized using controlled swelling measurements, aqueous degradation and dynamic mechanical analysis (DMA) as a function of independent parameters such as reaction condition, relative amount of curcumin diacrylate (CDA), amine crosslinker, diacrylate monomer and ratio of total acrylate to amine (RTAA).   In order to efficiently design PCβAE for specific biomedical applications, it is essential to understand the impact of synthesis conditions on the thermomechanical and drug release properties of these materials.

An improved film synthesis protocol based on ring casting with in-situpolymerization was developed to synthesize PCβAE films with reproducible network properties. Cross-linked polymer networks were formed by pre-polymerization of primary diamine with PEGDA in anhydrous organic solvent followed by addition of CDA. The liquid reaction mixture was deposited in an enclosed casting ring and incubated at 60°C in a convection oven, resulting in the formation of polymer films of thickness 0.1 to 0.3 mm.  The relative content of curcumin diacrylate in PCβAE was systematically varied from 0:100 (CDA:PEG400DA) to 90:10 (CDA:PEG400DA) using the same primary diamine (TTD) and an RTAA value of 1.0.  Curcumin, by its rigid character, alters the flexibility and architecture of the network, which then affects the degradation and release profile. An increase in CDA content resulted in an increase in glass transition temperature from -39°C to 67°C, as measured by DMA, and overall degradation times ranging from 3 hours to 24 hours were obtained. To assess the effect of length and relative hydrophilic character of the crosslinker on the hydrogel degradation and mechanical properties, three primary diamine crosslinkers viz. 4,7,10-trioxa-1,13-tridecanediamine (TTD), 2,2’(ethylenedioxy) bis ethylamine (EDBE) and hexamethylene diamine (HMD) were employed.  These were combined with commercial poly(ethylene glycol) diacrylates of varying molecular weight (diethylene glycol diacrylate (DEGDA), PEG400DA and PEG700DA) to provide a wide range of network structures for the incorporation of curcumin diacrylate with controlled release profiles.  A detailed discussion of the spectrum of performance properties accessible with these compositional variants will be presented.

References:

1.         Wattamwar PP, Biswal D, Cochran DB, Lyvers AC, Eitel RE, Anderson KW, Hilt JZ, and Dziubla TD. Acta Biomater 2012;8(7):2529-2537.