398705 Polymer Therapeutics for Protein Drug Delivery System

Monday, November 17, 2014
Galleria Exhibit Hall (Hilton Atlanta)
Adrian Salgado, Chemical Engineering, Prairie View A&M University, Prairie View, TX

A slow and controlled drug delivery system is vital to reducing the overall dosage amount and any toxic symptoms associated with the administration of drugs. The purpose of this research is to quantify and optimize the release of protein that has been incorporated within a Poly (vinyl alcohol) (PVA) membrane chemically cross-linked with Glutaraldehyde (GA) hydrogel to serve as a protein drug delivery system. A PVA-GA hydrogel membrane has a three-dimensional structure that allows the protein to permeate through the matrix. The open mesh created by GA results in advantageously high diffusivity that can be controlled by variations in the degree of crosslinking of the polymer matrix.  As a part of a development of a drug release system, this study investigates the extent of protein release from the polymeric network of the hydrogel into buffer solution of varied pH. The studied parameters include: the concentration of cross-linking agent (glutaraldehyde) of 0.75% and 1% (v/v), the concentration of protein (0.4 mg/mL and 0.7 mg/ml) and its overall effect on the swelling of the hydrogels, protein diffusion rate, and the release characteristics of the protein. Ovalbumin (OVAL) and Chicken Egg White Lysozyme (CEWL), 45kDa and 14.3kDa, were used as model proteins. Equilibrium Solution Content (ESC), Fourier Transform Infrared Spectroscopy (FTIR) and Thermal Gravimetric Analysis (TGA) characterized the protein-loaded membranes. The ESC experiments show that once protein is incorporated into the hydrogel matrix, the additional hydroxyl groups from the protein permitted additional interaction with the buffer solution and caused an increase in swelling and the mesh size. A higher concentration of protein at 0.7mg/ml resulted in a varied mesh size value. This data suggests that the pores were overloaded and resulted in a dynamic environment, which the protein moved in and out of the pores. Consequently, the 0.7mg/ml resulted in the highest release percentage of the diffusion experiments at 10% higher than the lower concentration of 0.4mg/ml. Also, the protein release demonstrates that from an initial pH 7.4, OVAL and CEWL prefer to diffuse into a buffer solution that is more alkaline of pH 8 than an acidic environment of pH 6.5. There was a 20% decline in the release within an acidic environment. The dissolution rate constant, kH and diffusion coefficient, D, confirm that the higher pH is a preferred environment as reported. The FTIR show that the protein within the hydrogel cannot be visualized or detected once chemical crosslinking has occurred. However, the TGA results indicate that this is a temporary phenomenon because thermal properties of the hydrogel are not affected by the incorporation of protein but rather chemical crosslinking does affect the thermal properties. The results indicate that the protein was successfully incorporated and the protein does diffuse from the membrane over time. Furthermore, the interaction between the hydrogel and protein is temporary and confirms that the membrane system is ideal for protein drug delivery. Although drug release systems have been studied, our objective is to investigate the mechanism of release and determine the efficiency as it correlates to membrane structure and environment. In our future studies, proteins of various sizes will be used to elucidate the protein release from the hydrogel network.

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