Fully biodegradable and cationic poly(amino oxalate) particles for the treatment of acetaminophen-induced acute liver failure.

Acute inflammatory diseases are one of major causes of death in the world and there is great need for developing drug delivery systems that can target drugs to macrophages and enhance their therapeutic efficacy. Poly(amino oxalate) (PAOX) is a new family of fully biodegradable polymer that possesses tertiary amine groups in its backbone and has rapid hydrolytic degradation. In this study, we developed PAOX particles as drug delivery systems for treating acute liver failure (ALF) by taking the advantages of the natural propensity of particulate drug delivery systems to localize to the mononuclear phagocyte system, particularly to liver macrophages. PAOX particles showed a fast drug release kinetics and excellent biocompatibility in vitro and in vivo. A majority of PAOX particles were accumulated in liver, providing a rational strategy for effective treatment of ALF. A mouse model of acetaminophen (APAP)-induced ALF was used to evaluate the potential of PAOX particles using pentoxifylline (PTX) as a model drug. Treatment of PTX-loaded PAOX particles significantly reduced the activity of alanine transaminase (ALT) and inhibited hepatic cell damages in APAP-intoxicated mice. The high therapeutic efficacy of PTX-loaded PAOX particles for ALF treatment may be attributed to the unique properties of PAOX particles, which can target passively liver, stimulate cellular uptake and trigger a colloid osmotic disruption of the phagosome to release encapsulated PTX into the cytosol. Taken together, we believe that PAOX particles are a promising drug delivery candidate for the treatment of acute inflammatory diseases.

The effect of VEGF on the myogenic differentiation of adipose tissue derived stem cells within thermosensitive hydrogel matrices.

We investigated the combination of human adipose tissue derived stem cells (ADSC) and in vivo gel-forming methoxy poly (ethyleneglycol)-poly (epsilon-caprolactone) (MPEG-PCL) as a muscle regeneration matrix, with and without inclusion of vascular endothelial cell growth factor (VEGF). VEGF(165)-treated stem cell grafts showed significant proliferation and differentiation into muscle tissue in vivo. Importantly, the inclusion of VEGF enhanced vascularization. This scaffold supported preconditioned ADSC, and allowed them to differentiate into mature muscle tissues in vivo, indicating that ADSC of human origin and MPEG-PCL scaffolds provided an appropriate environment for cellular growth and expansion. Our results thus provide a potential solution to the major obstacle encountered in the engineering of thick complex tissues, which require an adequate blood supply to maintain cell viability during tissue growth and to induce appropriate structural organization. Therefore, the combination of ADSC and in vivo gel-forming MPEG-PCL with VEGF(165) might serve as a suitable non-invasive biomaterial for clinical muscle regeneration applications.