Production of stable quinine nanodispersions using esterified γ-polyglutamic acid biopolymer

• B. licheniformis cultivation produces γ-PGA in high titer and purity that can be used in novel drug delivery systems.
• γ-PGA was modified to amphiphilic component acting as stabilizer with hydrophobic part by l-phenylalanine ethyl ester.
• THF solvent evaporation generates dispersion with P(γ-GA-r-l-PAE) as surfactant and quinine as hydrophobic model drug.
• Evaporation of THF induced nucleation process of pure quinine core surrounded by amphiphilic biopolymer.
• Potential of further pharmaceutical applications of stable dispersions with hydrophobically modified γ-PGA.

Novel methods are needed for the development of nanodispersed drug formulations to enhance bioavailability of many hydrophobic pharmaceuticals. The poorly water-soluble quinine is a well-known anti-malaria drug which can be used as a promising model compound for the development of novel nanodispersed formulations. In addition to hydrophobic drug's own affecting properties, surfactants play an important role for the enhancement of their low bioavailability by preparing stable dispersions. Amphiphilic compounds can efficiently be used to stabilize colloidal fragments by preventing the precipitation or crystallization of poorly water-soluble active ingredients during fabrication. A novel biopolymer derivative based on the biotechnologically produced γ-polyglutamic acid (γ-PGA) from Bacillus licheniformis cultivation was developed for encapsulation of the active ingredient. High-molecular γ-PGA is an anionic polyelectrolyte that was optimized and modified with hydrophobic l-phenylalanine ethyl ester (l-PAE) to form an amphiphilic comb polymer P(γ-GA-r-l-PAE) with surfactive properties. The approach of the nanodispersion polymer concentration, molecular weight and grafting degree enables the efficient stabilization of the poorly water-soluble model drug. The research presented in this report indicates the potential benefits of hydrophobically modified γ-PGA and suggests its potential role in forming stable dispersions for future pharmaceutical applications.