Polymers used in Drug Delivery Systems…
In recent years, controlled drug delivery formulations and the polymers used in these systems have become much more sophisticated, with the ability to do more than simply extend the effective release period for a particular drug. For example, current controlled-release systems can respond to changes in the biological environment and deliver—or cease to deliver—drugs based on these changes. In addition, materials have been developed that should lead to targeted delivery systems, in which a particular formulation can be directed to the specific cell, tissue, or site where the drug it contains is to be delivered. While much of this work is still in its early stages, emerging technologies offer possibilities that scientists have only begun to explore.
A range of materials have been employed to control the release of drugs and other active agents. The earliest of these polymers were originally intended for other, nonbiological uses, and were selected because of their desirable physical properties, for example:
- Poly(urethanes) for elasticity.
- Poly(siloxanes) or silicones for insulating ability.
- Poly(methyl methacrylate) for physical strength and transparency.
- Poly(vinyl alcohol) for hydrophilicity and strength.
- Poly(ethylene) for toughness and lack of swelling.
- Poly(vinyl pyrrolidone) for suspension capabilities.
To be successfully used in controlled drug delivery formulations, a material must be chemically inert and free of leachable impurities. It must also have an appropriate physical structure, with minimal undesired aging, and be readily processable. Some of the materials that are currently being used or studied for controlled drug delivery include
- Poly(2-hydroxy ethyl methacrylate).
- Poly(N-vinyl pyrrolidone).
- Poly(methyl methacrylate).
- Poly(vinyl alcohol).
- Poly(acrylic acid).
- Poly(ethylene-co-vinyl acetate).
- Poly(ethylene glycol).
- Poly(methacrylic acid).
However, in recent years additional polymers designed primarily for medical applications have entered the arena of controlled release. Many of these materials are designed to degrade within the body, among them
- Polylactides (PLA).
- Polyglycolides (PGA).
- Poly(lactide-co-glycolides) (PLGA).
Originally, polylactides and polyglycolides were used as absorbable suture material, and it was a natural step to work with these polymers in controlled drug delivery systems. The greatest advantage of these degradable polymers is that they are broken down into biologically acceptable molecules that are metabolized and removed from the body via normal metabolic pathways. However, biodegradable materials do produce degradation by-products that must be tolerated with little or no adverse reactions within the biological environment.
These degradation products—both desirable and potentially nondesirable—must be tested thoroughly, since there are a number of factors that will affect the biodegradation of the original materials. The most important of these factors are shown in the box below—a list that is by no means complete, but does provide an indication of the breadth of structural, chemical, and processing properties that can affect biodegradable drug delivery systems.
Factors affecting BIO-DEGRADATION of Polymers
- Chemical structure.
- Chemical composition.
- Distribution of repeat units in multimers.
- Presents of ionic groups.
- Presence of unexpected units or chain defects.
- Configuration structure.
- Molecular weight.
- Molecular-weight distribution.
- Morphology (amorphous/semi crystalline, microstructures, residual stresses).
- Presence of low-molecular-weight compounds.
- Processing conditions.
- Sterilization process.
- Storage history.
- Site of implantation.
- Adsorbed and absorbed compounds (water, lipids, ions, etc.).
- Physicochemical factors (ion exchange, ionic strength, and pH).