Photopatternable Biodegradable Aliphatic Polyester with Pendent Benzophenone Groups.

Highly efficient photo-cross-linking reactions enable numerous applications in biomaterials. Here, a photopatternable biodegradable aliphatic polyester with benzophenone pendent groups was synthesized by copper-catalyzed alkyne-azide cycloaddition, affording polyesters that undergo UV-induced cross-linking to yield photopatterned films. Using this material, a self-folding multilayer structure containing polyester/hydrogel bilayer hinges was fabricated. Upon swelling of the hydrogel layer, the construct folds into a triangular tube, which subsequently unfolds due to lipase-catalyzed degradation of the polyester layer. The ability to precisely design such degradation-induced structural changes offers potential for biomaterials and medical applications, such as evolving and responsive 2D and 3D tissue engineering scaffolds.

Synthesis and evaluation of cyclosporine A-loaded polysialic acid-polycaprolactone micelles for rheumatoid arthritis.

Polysialic acid (PSA) has been identified as a natural, hydrophilic polymer that can be used to extend circulation time and improve therapeutic efficacy when used as the basis of drug carrier systems. Here, to further investigate the potential of PSA to alter the pharmacokinetic and pharmacodynamic profiles of associated therapeutics, PSA-based micelles were formed via self-assembly of PSA grafted with polycaprolactone (PCL) at a critical micelle concentration of 84.7±13.2 µg/ml. Cyclosporine A (CyA), a therapeutic used in the treatment of rheumatoid arthritis, was loaded into the PSA-PCL micelles with a loading capacity and loading efficiency of 0.09±0.02 mg CyA/mg PSA-PCL and 29.3±6.4%, respectively. CyA loading resulted in a size increase from 73.8±12.4 nm to 107.5±9.3 nm at 25 °C and from 138.4±40.7 nm to 195.3±52.1 nm at 37 °C, favorable size ranges for drug delivery to inflamed tissue characterized by leaky vasculature, as occurs during rheumatoid arthritis pathogenesis. As an indicator of the stealth nature the micelles are expected to exhibit in vivo, the fixed aqueous layer thickness of the PSA-PCL micelles was determined to be 0.63±0.02 nm, comparable to that obtained for traditionally utilized poly(ethylene glycol) coated liposomes. The PSA-PCL micelles had a negligible effect on the viability of the SW982 synovial fibroblast cell line. Fluorescent microscopy was utilized to demonstrate uptake by the synovial fibroblasts through a non-receptor mediated form of endocytosis and partitioning of CyA into the membrane.

Polysialic acid-based micelles for encapsulation of hydrophobic drugs.

Despite improvements relative to unmodified counterparts, poly(ethylene glycol) (PEG) conjugation may not be the ideal solution for improving circulatory stability of current nanoparticle carriers or free drugs. Polysialic acid (PSA), a natural polymer for which the body possesses no receptors, has been conjugated directly to biologically active molecules to prevent premature clearance; however, this concept has not yet been applied to nanoparticle drug carrier systems. In the current study, PSA was modified with a long-chain hydrocarbon through reaction of the carboxylic acid side groups with N-decylamine (DA). The resultant PSA-DA conjugates self-assembled into micelles for encapsulation of hydrophobic drug molecules, as demonstrated with Cyclosporine A. Cytotoxicty was dependent on the degree of substitution with DA. On the basis of size and zeta potential, the micelles are capable of passively targeting diseased regions, such as cancer and inflammatory tissue. Further investigations are necessary to explore whether the PSA-based micelles possess stealth properties similar to those of PEG and to establish in vitro and in vivo efficacy.