Design and evaluation of a novel nanoparticulate-based formulation encapsulating a HIP complex of lysozyme

Abstract

Formulation development of protein therapeutics using polymeric nanoparticles has found very little success in recent years. Major formulation challenges include rapid denaturation, susceptibility to lose bioactivity in presence of organic solvents and poor encapsulation in polymeric matrix. In the present study, we have prepared hydrophobic ion pairing (HIP) complex of lysozyme, a model protein, using dextran sulfate (DS) as a complexing polymer. We have optimized the process of formation and dissociation of HIP complex between lysozyme and DS. The effect of HIP complexation on enzymatic activity of lysozyme was also studied. Nanoparticles were prepared and characterized using spontaneous emulsion solvent diffusion method. Furthermore, we have also investigated release of lysozyme from nanoparticles along with its enzymatic activity. Results of this study indicate that nanoparticles can sustain the release of lysozyme without compromising its enzymatic activity. HIP complexation using a polymer may also be employed to formulate sustained release dosage forms of other macromolecules with enhanced encapsulation efficiency.

Keywords::

• Lysozyme
• HIP complex
• nanoparticles

Acknowledgments

The authors are thankful to Dr. Elisabet Kostoryz, School of Dentistry for helping us in dynamic light scattering study.

Declaration of interest

This work was supported by the National Institutes of Health grants R01 EY 09171-16 and R01 EY 10659-14. The authors report no conflicts of interest.