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Polyurethanes (PUs) are formed by a reaction between isocyanates and diols to yield polymers with urethane bonds (-NH-COO-) in their main chain. A great variety of building blocks is commercially available that allows the chemical and physical properties of PUs to be tailored to their target applications, particularly for the biomedical and pharmaceutical fields. This article reviews the synthesis and characterization of PUs and PU-copolymers, as well as their in vitro and in vivo biodegradability and biocompatibility. Particular emphasis is placed on the use of PUs for the controlled release of drugs and for the (targeted) delivery of biotherapeutics., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This paper describes the development of a stable pharmaceutical dosage form for NAMI-A, a novel antimetastatic ruthenium complex, for Phase I testing. NAMI-A drug substance was characterized using several spectrometric and chromatographic techniques. In preformulation studies, it was found that NAMI-A in aqueous solution was not stable enough to allow sterilization by moist heat. The effect of several excipients on the stability of the formulation solution was investigated. None of them provided sufficient stability to allow long-term storage of an aqueous solution of NAMI-A. Therefore, a lyophilized product was developed. Five different formulations were prepared and subjected to thermogravimetric (TG) analysis and stability studies at various conditions for 1 year. Minimal degradation during the production process is achieved with a formulation solution of pH 3-4. Of the acids tested, only hydrochloric acid (HCl 0.1 mM) both stabilized the formulation solution and was compatible with the lyophilized product. This product was stable for at least 1 year when stored at -20 degrees C, 25 degrees C/60% relative humidity (RH) and 40 degrees C/75% RH, and was also photostable.

To preserve the size and transfection potential of polymer-plasmid complexes. Freeze-drying and freeze-thawing were used for stabilization of these complexes. The concentration of the sugars is an important factor affecting both the size and transfection capability of the complexes after freeze-drying and freeze-thawing. However, the type of lyoprotectant (sugar) used is of minor importance. It is also shown that when damage to polymer-plasmid complexes occurs, it results from the drying process but is not due to the freezing step.

Freeze-drying of three different forms of gene delivery systems was performed using a controlled two-step drying process and 10% sucrose as lyoprotectant. Complexes of pCMVL plasmid with transferrin-conjugated polyethylenimine, adenovirus-enhanced transferrinfection consisting of pCMVL/transferrin-polylysine complexes linked to inactivated adenovirus particles, and a recombinant, E1-defective adenovirus expressing a luciferase reporter gene were tested. Three weeks after freeze-drying the reagents were rehydrated with water and tested for transfection activity. Luciferase gene expression levels were retained at high levels in all three systems, in contrast to reagents stored in solution. The use of the lyoprotectant was essential. In the absence of sucrose the transfection activities dropped by a factor of 100-1000. The data suggest freeze-drying as a useful method for stabilization and storage of standardized batches of transfection agents.