A sustained release formulation of chitosan modified PLCL:poloxamer blend nanoparticlesloaded with optical agent for animal imaging

Abstract

The objective of this study was to develop optical imaging agent loadedbiodegradable nanoparticles with indocynanine green (ICG) using chitosan modifiedpoly(L-lactide-co-epsilon-caprolactone) (PLCL):poloxamer (Pluronic F68) blendedpolymer. Nanoparticles were formulated with an emulsification solvent diffusion techniqueusing PLCL and poloxamer as blend-polymers. Polyvinyl alcohol (PVA) and chitosan wereused as stabilizers. The particle size, shape and zeta potential of the formulatednanoparticles and the release kinetics of ICG from these nanoparticles were determined.Further, biodistribution of these nanoparticles was studied in mice at varioustime points until 24 h following intravenous administration, using a non-invasiveimaging system. The average particle size of the nanoparticles was found to be146 ± 3.7 to260 ± 4.5 nm. The zeta potential progressively increased from − 41.6 to + 25.3 mV with increasing amounts of chitosan. Particle size and shape of the nanoparticles werestudied using transmission electron microscopy (TEM) which revealed the particles to besmooth and spherical in shape. These nanoparticles were efficiently delivered to thecytoplasm of the cells, as observed in prostate and breast cancer cells using confocal laserscanning microscopy. In vitro release studies indicated sustained release of ICG from thenanoparticles over a period of seven days. Nanoparticle distribution results in miceshowing improved uptake and accumulation with chitosan modified nanoparticles invarious organs and slower clearance at different time points over a 24 h periodas compared to unmodified nanoparticles. The successful formulation of suchcationically modified nanoparticles for encapsulating optical agents may lead to apotential deep tissue imaging technique for tumor detection, diagnosis and therapy.