Drug-eluting medical implants are actually active implants that induce healing effects, in addition to their regular task of support. This effect is achieved by controlled release of active pharmaceutical ingredients (API) into the surrounding tissue. In this chapter we focus on three types of drug-eluting devices: drug-eluting vascular stents, drug-eluting wound dressings and protein-eluting scaffolds for tissue regeneration, thus describing both internal and external implants. Each of these drug-eluting devices also presents an approach for solving the drug release issue. Most drug-eluting vascular stents are loaded with water-insoluble antiproliferative agents, and their diffusion from the device to the surrounding tissue is relatively slow. In contrast, most drug-eluting wound dressings are loaded with highly water-soluble antibacterial agents and the issue of fast release must therefore be addressed. Growth factor release from scaffolds for tissue regeneration offers a new approach of incorporating high-molecular-weight bioactive agents which are very sensitive to process conditions and preserve their activity during the preparation stage. The drug-eluting medical implants are described here in terms of matrix formats and polymers, incorporated drugs and their release profiles from the implants, and implant functioning. Basic elements, such as new composite core/shell fibers and structured films, can be used to build new antibiotic-eluting devices. As presented in this chapter, the effect of the processing parameters on the microstructure and the resulting drug release profiles, mechanical and physical properties, and other relevant properties, must be elucidated in order to achieve the desired properties. Newly developed implants and novel modifications of previously developed approaches have enhanced the tools available for creating clinically important biomedical applications.
Climate chambers have been widely used in in vitro and in vivo studies which require controlled environmental temperature and humidity conditions. This article describes a new desktop climate chamber that was developed for application of respiratory airflows on cultured nasal epithelial cells (NEC) under controlled temperature and humidity conditions. Flow experiments were performed by connecting the climate chamber to an airflow generator via a flow chamber with cultured NEC. Experiments at two controlled climate conditions, 25 • C and 40% relative humidity (RH) and 37 • C and 80%RH, were conducted to study mucin secretion from the cultures in response to the flow. The new climate chamber is a relatively simple and inexpensive apparatus which can easily be connected to any flow system for climate controlled flow experiments. This chamber can be easily adjusted to various in vitro experiments, as well as to clinical studies with animals or human subjects which require controlled climate conditions.
For many biomedical applications, there is need for porous implant materials. The current article focuses on a method for preparation of drug-eluting porous structures for various biomedical applications, based on freeze drying of inverted emulsions. This fabrication process enables the incorporation of any drug, to obtain an “active implant” that releases drugs to the surrounding tissue in a controlled desired manner. Examples for porous implants based on this technique are antibiotic-eluting mesh/matrix structures used for wound healing applications, antiproliferative drug-eluting composite fibers for stent applications and local cancer treatment, and protein-eluting films for tissue regeneration applications. In the current review we focus on these systems. We show that the release profiles of both types of drugs, water-soluble and water-insoluble, are affected by the emulsion's formulation parameters. The former's release profile is affected mainly through the emulsion stability and the resulting porous microstructure, whereas the latter's release mechanism occurs via water uptake and degradation of the host polymer. Hence, appropriate selection of the formulation parameters enables to obtain desired controllable release profile of any bioactive agent, water-soluble or water-insoluble, and also fit its physical properties to the application.
Poly(DL-lactic-co-glycolic acid) microspheres are prepared using a double-emulsion technique and are loaded with the model enzyme horseradish peroxidase (HRP). These microspheres can be used alone or as coatings for bioresorbable fibers that may be used as scaffolds for tissue regeneration applications. The present study focuses on the effect of the copolymer's composition and initial molecular weight on the microsphere structure, encapsulation efficiency, and cumulative protein release for 12 weeks. The release profiles generally exhibits an initial burst effect accompanied by slow release over an extended period of time, during which diffusion rather than degradation controlled HRP release from these structures. An increase in the initial molecular weight or in the copolymer's lactic acid content results in larger microspheres with smoother surfaces, and a decrease in the burst release and in the total HRP release. Molecular weight is found to have a stronger effect than copolymer composition. We demonstrate that it is possible to obtain versatile release profiles, which can be tailored for specific applications by choosing the right initial molecular weight and copolymer composition.
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