Liquid crystalline nanoparticles for drug delivery: The role of gradient and block copolymers on the morphology, internal organisation and release profile

Abstract

Amphiphilic polymers represent one of the main class of stabilizers for non-lamellar lyotropic liquid crystalline nanoparticles, being essential for their formation and stability. In the present study, poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) block copolymers and poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) (MPOx) gradient copolymers were incorporated as stabilizers in liquid crystalline nanoparticles prepared from glyceryl monooleate. The polymers were chosen according to their high biocompatibility and promising stealth properties, in order to develop safe and efficient drug delivery nanosystems. The physicochemical characteristics and fractal dimension of the resultant nanosystems were obtained from light scattering techniques, while their micropolarity and microfluidity from fluorescence spectroscopy. The effect of temperature, serum proteins and ionic strength on the physicochemical behavior was monitored. Their morphology was assessed by cryo-TEM, while their thermal behavior by microcalorimetry and high-resolution ultrasound spectroscopy. Their properties were dependent on the stabilizer chemistry and topology (block/gradient copolymer) and its concentration. Subsequently, resveratrol, as model hydrophobic drug, was loaded into the nanosystems, the entrapment efficiency was calculated and in vitro release studies were carried out, highlighting how the different stabilizer can differentiate the drug release profile. In conclusion, the proposed copolymers broaden the toolbox of polymeric stabilizers for the development of liquid crystalline nanoparticles intended for drug delivery applications.