Property modelling of lysozyme-crosslinker-alginate complexes using latent variable methods.

Statistical methods were used to provide insight into a polymer complex system composed of lysozyme and alginate to quantify the effects of such parameters as pH, and ionic composition of the mixing solution on the properties of the complexes including composition, particle diameter, and zeta potential. Various crosslinkers (calcium, barium, iron[III], and bovine serum albumin), were used with lysozyme for complex formation to investigate the effect of crosslinker charge density on protein release kinetics, modelled using ktn . Multivariate statistical analysis showed that the kinetic parameters associated with the release were, not surprisingly highly dependent on the ionic strength of the release media, with higher ionic strength leading to faster release. The release parameter k was also shown to depend on the protein properties (size, ionic strength) while n was slightly, but not statistically dependent on the charge density of the crosslinker demonstrating that the nature of the crosslinker had minimal impact on drug release. The multivariate statistical has the potential to be used for optimization of the complexes and prediction of physical properties and degradation rates.

PEG-containing siloxane materials by metal-free click-chemistry for ocular drug delivery applications.

Metal-free click-chemistry can be used to create silicone hydrogels for ocular drug delivery applications, imparting the benefits of silicones without catalyst contamination. Previous work has demonstrated the capacity for these materials to significantly reduce protein adsorption. Building upon this success, the current work examines and optimizes different materials in terms of their protein adsorption and drug release capabilities. Specifically, incorporating lower molecular weight poly-ethylene glycol (PEG) is better able to reduce protein adsorption. However, with higher molecular weight PEG, the materials exhibit excellent water content and better drug release profiles. The lower molecular weight PEG is also able to deliver the drug over a period in excess of four months, with the amount of crosslinking having the greatest impact on the amount of drug release. Overall, these materials show great promise for ocular applications.

Protein-alginate complexes as pH-/ion-sensitive carriers of proteins.

Protein-alginate complexes were prepared with the objective of quantifying the influence of the parameters such as protein characteristics on the final complex properties and their dissociation rates. Cytochrome C, lysozyme, myoglobin, chymotrypsin, and bovine serum albumin were used as model proteins for preparing the complexes and physical properties such as composition, average diameter, and zeta potential of the complexes formed were measured. In addition, protein release kinetics from the complexes in response to changes in pH and ionic strength were investigated. The results clearly demonstrated that, even in the absence of a cation, proteins could be complexed with alginate and showed a decreased release rate under the appropriate conditions. Projection to Latent Structures was applied as a multivariate statistical analysis method to mathematically describe the final properties and the protein release kinetics as a function of the influencing variables. It was found that the physical characteristics of the complexes could be accurately modelled with low error thresholds indicative of good fit and prediction capabilities of the model. The statistical model indicated that the release kinetics parameters were highly dependent on the ionic strength and the protein net charge as a function of pH, demonstrating the potential use of these complexes in ion-/pH-sensitive delivery systems.

Optimizing electrostatic interactions for controlling the release of proteins from anionic and cationically modified alginate.

Alginate and cationically modified alginate microparticles were prepared with the goal of developing hydrogel microparticles that offer controlled release of protein drugs mainly by modification of the absolute charge of the hydrogel network. Protein loading and release studies were carried out using model proteins with different net charges (i.e. low, high, and neutral isoelectric points) covering a broad range of molecular weights. The Projection to Latent Structures (PLS) method was used for qualitatively and quantitatively describing the relationships between the properties of proteins such as net charge and molecular weight, polymer properties including degree of substitution and microparticle size, and the release kinetics (ktn). It was found that electrostatic interactions and protein molecular weight had the greatest impact on parameter k while parameter n was mostly affected by polymer and buffer properties. In addition to understanding the current trends, the multivariate statistical method also provided an effective and reliable model as a beneficial tool for predicting and optimizing protein delivery systems.