(673e) Understanding the Encapsulation and Release Properties of Chitosan Microgels

Chitosan microgels have attracted considerable attention as vectors for both small molecule and macromolecular therapeutics. Yet, their encapsulation and release properties are tuned by trial and error. To develop quantitative guidelines for predicting their loading capacities and release rates, we have examined the relationship between the strength and stoichiometry of the drug-microgel binding and the microgel encapsulation/release characteristics. The microgels (ca. 200 nm in diameter) were prepared through ionotropic gelation of chitosan with tripolyphosphate (TPP). The binding of a model drug (aspirin) to the microgels was then quantified at various NaCl concentrations by isothermal titration calorimetry (ITC), and used to develop Langmuir model-based expressions that predict the drug loading capacity and encapsulation efficiency. These expressions yield fair agreement with experimental data, and suggest ITC to be a useful tool for predicting drug loading within biopolymer microgels. Additionally, we have characterized the in vitro release profiles using the standard “solvent replacement” method, where the solvent was periodically replaced with fresh buffer and analyzed for the released drug content. Repeating these measurements at various solvent replacement frequencies revealed that equilibrium between the microgel and solvent phases is reached much faster than the solvent can be replaced. This reflects the high solute diffusivities and small diffusion distances within the microgels, and suggests the apparent release profiles that are routinely measured by the solvent replacement method to be artifacts of the sampling frequency.