Effect of Hydrophobicity of Biodegradable Poly(Lactic-Co-Glycolic Acid) Polymer on Nanoparticle Surface-Protein Interactio

In spite of rapidly growing peptide and protein drugs in the market, their limited therapeutic applications are due to the undesirable interaction between protein and solid surface which may not only reduce therapeutic effect but can also lead to undesirable side effects. Interaction of recombinant human growth hormone (r-hGH) with protein coated surfaces and non-biodegradable polymer surfaces have been previously investigated. However, our goal is to obtain a detailed understanding of protein and biodegradable polymer surface interaction which can provide crucial dual advantage of developing successful delivery system while reducing the polymer toxicity. The present work involves qualitative and quantitative characterization of the adsorption of r-hGH onto Poly (lactic-coglycolic) acid (PLGA) polymers with a different degree of hydrophobicity. Interaction of r-hGH with PLGA of different hydrophobicity under varying conditions of pH was studied using (dynamic light scattering-DLS and zeta potential), spectroscopic (fluorescence and Circular Dichroism), equilibrium dialysis and thermal (isothermal titration calorimetry-ITC) techniques in order to characterize the structural changes and adsorption isotherm. The adsorption of r-hGH onto PLGA was found to be sensitive to pH and exhibited differences in behavior for adsorption onto PLGA due to differences in degree of hydrophobicity and magnitude of charge distribution on the PLGA surface. Overall, the adsorption behavior was complex and influenced by a number of processes under the experimental conditions such as a) electrostatic interactions b) hydrophobic interactions c) hydrogen bond formation d) structural changes of r-hGH upon adsorption e) removal of water molecules and incorporation of ions at the contact layer. The results of experiments indicated that the most favorable interactions with least structural changes are observed with PLGA 50501A and PLGA 8515 3CE Nanoparticles at pH 7.2.