Biomaterials for local drug delivery in central nervous system.

The central nervous system (CNS) is a vital part of human body which coordinate the actions by transmitting signals. Because of the existence of the blood-brain barrier and the blood-spinal cord barrier, diseases in CNS can hardly be directly intervened by non-invasive methods. While systemic delivery usually requires extravagant drug dosage and leads into toxicity in unexpected tissues, local drug delivery in CNS tissues provides a solution for the problems of physiological barriers and systematic side effects. Biomaterials are applied in local drug delivery system (LDDS) for CNS disease therapy with aims of tuning the drug release property and improving bioavailability, solubility, stability and safety of pharmaceutics. The indispensable importance and distinct physiological structure of cerebrospinal area bring about challenges to biomaterials in LDDS. Thus, properties of drug delivery systems are necessitated with prudently concern. In this review, the development of LDDS utilizing biomaterials will be presented, including sustained release, local parameter-responsible release, and regional cell-selective active targeting release. Studies on biomaterials employed as pharmaceuticals will give rise to a more efficacious method and the better understanding of LDDS design in CNS.

α-chymotrypsin activated and stabilized by self-assembled polypseudorotaxane fabricated with bis-thiolated poly(ethylene glycol) and α-cyclodextrin: Spectroscopic and mechanistic analysis.

The self-assembled polypseudorotaxane (PPRX) fabricated with bis-thiolated poly(ethylene glycol) (PEG) and α-cyclodextrin (α-CyD) acted as an activator for α-chymotrypsin (CT) and retained the activity of CT for a long time up to 7days. The stabilization mechanism was studied, and the interaction between CT and PPRX was analyzed by using circular dichroism, fluorescence spectra and X-ray powder diffraction (XRD). The bis-thiolated PEG and its assembled PPRX with α-CyD exhibited the interaction with the C-terminal region of the CT's B-chain probably through PEGylation of the surface disulfide bridge of CT. It caused the aromatic chromophores more exposed to the hydrophilic microenvironment, leading to conformational variation of CT that was revealed by spectroscopic analysis. It rendered the peptide chains in a more flexible and active state. As a comparison, the non-thiolated components could not decorate the surface of CT and performed almost no effect on its stability, which demonstrated that the decoration of the surface disulfide bridge was a key factor in retaining the activity of CT. Due to the activation and stabilization effect, bis-thiolated PEG/α-CyD PPRX was an excellent soft-immobilized carrier for CT, and provided an intriguing method for enzyme's stabilization.