Polyelectrolyte Multi-Layered Griseofulvin Nanoparticles: Conventional versus Continuous In-Situ Layer-by-Layer Fabrication.

Abstract

Polyelectrolyte multilayers are promising drug carriers with potential applications in the delivery of poorly soluble drugs. Furthermore, the polyelectrolyte multilayer contributes towards electrostatic interactions, which enhances the physical and chemical stability of colloids when compared to those prepared by other approaches. The aim of this work was to generate a polyelectrolyte multilayer on well characterised nanoparticles of the poorly water-soluble drug, griseofulvin. Griseofulvin (GF) nanoparticles (300 nm) were produced by wet bead milling, bearing a negative surface charge due to the use of poly(sodium 4-styrenesulfonate) (PSS) as a stabiliser. Six further layers of alternating chitosan and PSS polyelectrolyte multilayer were successfully generated at the particle surface either via use of: (1) the conventional method of adding excess coating polymer followed by centrifugation, or (2) the continuous in situ approach of adding sufficient amount of coating polymer. The continuous in situ method was designed de novo by the consecutive addition of polymers under high shear rate mixing. In comparison to the continuous in situ method, the conventional method yielded nanoparticles of smaller size (282 ±9 nm vs. 497 ±34 nm) and higher stability by maintaining its size for 6 months. In conclusion, the parent griseofulvin nanosuspension proved to be a suitable candidate for the polyelectrolyte multilayer fabrication providing an avenue for a bespoke formulation with versatile and potentially enhanced drug delivery properties.