PVAX copolymer and PVAX microparticles comprising the same

#The present application is the 35 U.S.C. §371 national phase application pursuant to 35 U.S.C. §371, of PCT International Application No. PCT/US2013/062627, filed Sep. 30, 2013, designating the United States and published in English, which claims priority to International Application No. PCT/KR2013/006930, filed Aug. 1, 2013, and published under PCT Article 21(2) in English, which claims priority to Korean Application No. 10-2012-0108696, filed Sep. 28, 2012, all of which applications are hereby incorporated by reference in their entireties herein.

#Several biodegradable polymers have found use in the field of tissue engineering, because of their attractive physical, chemical, biological and mechanical properties. Polymers useful in tissue engineering may be divided into the groups of natural polymers and synthetic polymers.

#Natural polymers include, but are not limited to, collagen, hyaluronic acid, alginate, gelatin, xanthan gum, keratin, and small intestinal submucosa. These polymers have good biocompatibility and are unlikely to induce an immune response after transplantation. However, the mechanical properties of natural polymers are not completely satisfactory.

#The following detailed description of preferred embodiments of the invention will be better understood when read in conjunction with the appended drawings. For the purpose of illustrating the invention, there are shown in the drawings embodiments that are presently preferred. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities of the embodiments shown in the drawings.

#FIG. 1 illustrates the 1H NMR spectrum of a vanillyl alcohol-containing copolyoxalate copolymer (or PVAX).

#FIG. 2 is a scanning electron microscope (SEM) photograph illustrating the shape of PVAX microparticles.

#The present invention relates to the unexpected discovery of novel vanillyl alcohol-containing copolyoxalate copolymers (also known as PVAX). The present invention further relates to the unexpected discovery of a PVAX microparticle comprising a PVAX copolymer. In one embodiment, the compositions of the invention are useful as drug delivery systems or contrast agents. In one embodiment, the compositions of the invention are useful in diagnosing, treating and/or preventing oxidative-related diseases, inflammation, ischemic disease and side effects of anticancer drugs.

#In one embodiment, the copolymer of the invention comprises vanillyl alcohol (also known as 4-hydroxymethyl-2-methoxy-phenol, 4-hydroxy-3-methoxybenzyl alcohol or VA) as a monomer (or building block). In another embodiment, the copolymer of the invention comprises oxalic acid, 1,4-cyclohexamethanol and vanillyl alcohol as monomers (or building blocks).

#In one aspect, the copolymers of the invention are non-toxic, are biocompatible and are degraded under physiological conditions while releasing vanillyl alcohol. Without wishing to be limited by theory, the release of vanillyl alcohol or a derivative thereof by degradation of the copolymer of the invention accounts at least in part for the anti-oxidative, anti-inflammatory and anti-apoptotic effects of the copolymer; the preventive or ameliorative effect on side effects of anticancer drugs (such as hepatic or cardiac abnormalities) by the copolymer; and the copolymer's ability to detect hydrogen peroxide in vivo.