Background
Hydrogels are hydrophilic polymer networks with the ability to absorb water up to thousands of times their dry weight. Due to their biocompatibility, mechanical properties and capacity of interaction with soft biological tissues, they have been considered for an extensive range of biomedical applications, including soft contact lenses, wound and burn dressings and cartilage substitutes.
Figure 1: Examples of biomedical applications of hydrogels: contact lenses, breast implants, wound dressings.
In the last years, it was observed a rising interest in using hydrogels as platforms for local drug delivery. They demonstrated to be quite versatile as carriers of growth factors, proteins, antimicrobials and other drugs. To achieve a continuous and sustained drug release from hydrogels, several studies focused on the development of surface and bulk modifications, e.g. conventional coating, grafting of specific monomers, crosslinking of the surfaces by UV, gamma irradiation and plasma treatments or incorporation of compounds with different charge or hydrophobicity, such as surfactants, vitamin E and cyclodextrins.
Figure 2: Schematic diagram of strategies commonly used to improve drug release behavior from drug loaded CLs: (1) - Soaking, (2) - Incorporation of diffusion barriers such as vitamin E, (3) -Incorporation of ligands/functional monomers in the polymeric matrix, (4) - Surface coating by multi-layering colloidal nanoparticles and ligands, (5) - Molecular imprinting and (6) - Incorporation of drug-loaded nanoparticles or other colloidal nanostructured systems.
A major problem faced by the manufacturers of hydrogel based medical devices is the sterilization procedure. In fact, medical device related infections are a major problem in health care, and minimization of these infections relies on efficient sterilization of all materials that contact/are placed into the body. Potential sources of microbial contamination during production of the devices include the raw materials, equipment and processes used, in addition to the facilities and personnel. Hydrogel devices are generally sterilized through conventional methods as exposition to saturated steam under pressure, gamma radiation or chemical agents (e.g. hydrogen peroxide, ethanol or ethylene oxide), but new methods may bring technical and economic advantages. For example, ozone, a powerful oxidant, has been used for water decontamination as well as for air and food sterilization, but till date was never applied to hydrogels.
Figure 3: Commonly used methods for sterilization of medical devices.
Due to hydrogels nature, concerns have raised regarding the undesirable effects that the sterilization procedures may have on the materials properties. More, when used as drug carriers, additional problems related with the effect that sterilization may have on the drug release and on the drug activity may emerge. Recent studies demonstrated that sterilization affects differently the drug release profiles, depending on the pair of drug-hydrogel, which means that a careful investigation has to be done for each specific system. Therefore, it is very important to gather detailed knowledge on the response of modified drug loaded materials to sterilization methods, in order to achieve increasingly safer, sterile and effective hydrogels.