Novel 2-methoxyacylhydrazones as potent, selective PDE10A inhibitors with activity in animal models of schizophrenia.

A series of 2-methoxyacylhydrazones were optimized to yield compounds with high affinity for PDE10A. Several compounds demonstrated efficacy in animal models of schizophrenia, including conditioned avoidance response and a pro-psychotic phencyclidine hyperactivity model.

Molecularly engineered poly(ortho ester) microspheres for enhanced delivery of DNA vaccines.

Genetic vaccination using plasmid DNA presents a unique opportunity for achieving potent immune responses without the potential limitations of many conventional vaccines. Here we report the design of synthetic biodegradable polymers specifically for enhancing DNA vaccine efficacy in vivo. We molecularly engineered poly(ortho ester) microspheres that are non-toxic to cells, protect DNA from degradation, enable uptake by antigen-presenting cells, and release DNA rapidly in response to phagosomal pH.

Post surgical pain management with poly(ortho esters).

Poly(ortho esters), POE, are synthetic bioerodible polymers that can be prepared as solid materials, or as viscous, injectable polymers. These materials have evolved through a number of families, and the latest member of this family, POE IV, is particularly well suited to drug delivery since latent acid is integrated into the polymer backbone, thereby, modulating surface erosion. POE IV predominantly undergoes surface erosion and is able to moderate drug release over periods from days to many months.

Development of poly(ortho esters) and their application for bovine serum albumin and bupivacaine delivery.

The preparation of drug delivery devices using solventless fabrication procedures is of significant interest and two such procedures are described. In one such procedure, powdered polymer and micronized protein are intimately mixed and then extruded into 1 mm strands that are cut to the desired length. The polymers used were specifically designed to allow extrusion at temperatures where proteins maintain activity in the dry state.