Biodegradable nanoparticles as nanomedicines: are drug-loading content and release mechanism dictated by particle density?

Abstract

We wish to highlight in this contribution our concerns regarding the low-loading contents of drug-loaded polymeric nanoparticles when the assemblies are manufactured by the straightforward method of nanoprecipitation. We have scanned a number of formulation variables in order to understand the influence of PCL and PLGA nanoparticle’s features on loading content, loading efficiency, and probe release profile. It was possible to produce coumarin-6-loaded particles with loading efficiency over 50%. Nevertheless, whatever the condition, the loading content never reached values higher than 0.4% w/w. The detailed structural characterization of the assemblies as performed via scattering techniques suggested that particle density is always notably low (from 0.06 to 0.34 g cm−3 depending on the variables of preparation) highlighting that the polymer chains making the assemblies are loosely packed and therefore highly swollen by water (from 72% up to 95% v/v). Our observations imply that the straightforward and simple nanoprecipitation protocol conducts to manufactured particles of notably low density which may significantly impact their loading capability and gives rise to reconsiderations of this approach. The experimental investigations also demonstrated that the probe release is essentially governed by a simple Fickian diffusion mechanism. Accordingly, the degradability may only have effects on polymer clearance within a biological environment, but not on sustained release or release profile.