Alginate and other hydrogels are attractive materials for a variety of biomedical applications, including cell transplantation, and drug delivery. In many of these applications one desires to either seed cells into the material, or allow for cellular invasion following implantation into the body. However, alginate is typically used in the physical form of a hydrogel, with small pores (nm size scale) that do not allow for cell movement in or out of the material.
Researchers at Michigan have invented modifications to alginates and other polysaccharide gels which can be used to obtain a variety of release profiles with release times ranging from a few days to several months. The processing technique also decreases the molecular weight of the constituent chains (which are then stabilized by cross-linking) to make the material completely biodegradable in addition to biocompatible. The extent of cross-linking and the presence of divalent cations can be adjusted to tailor the mechanical properties and degradation rate of the gels. Drugs may be bound to these gels in several ways such as via degradable, covalent bonds; ionically; or free in the matrix to allow diffusion-controlled release. A second part of this invention involves modifying polymers such as poly(vinyl alcohol) (PVA) so that they can reversibly bind several molecules of drug per molecule of polymer. These conjugates can be injected as prodrugs which will give a sustained release of active drug over time. This method may decrease the toxicity of the free drug, economize on the amount of drug given by increasing circulation time, and help to solubilize hydrophobic drugs. Molecular weight of the backbone may be adjusted to achieve different average circulation times.
Applications and Advantages
- Delivery of localized drugs following angioplasty to prevent smooth muscle proliferation
- Delivery of chemotherapy drugs, growth factors for localized vascularization, steroids for contraception or hormone replacement therapy or for treatment of rheumatoid arthritis
- Completely biodegradable and biocompatible
- High level of flexibility with respect to modifications