Understanding how nanoparticle properties such as size, morphology and rigidity influence their circulation time and biodistribution is essential for the development of nanomedicine therapies. Herein we assess the influence of morphology on cellular internalization, in vivo biodistribution and circulation time of nanocarriers using polystyrene-b-poly(ethylene oxide) micelles of spherical or elongated morphology. The glassy nature of polystyrene guarantees the morphological stability of the carriers in vivo and by encapsulating Indium-111 in their core, an assessment of the longitudinal in vivo biodistribution of the particles in healthy mice is performed with single photon emission computed tomography imaging. Our results show prolonged blood circulation, longer than 24 hours, for all micelle morphologies studied. Dynamics of micelle accumulation in the liver and other organs of the reticuloendothelial system show a size-dependent nature and late stage liver clearance is observed for the elongated morphology. Apparent contradictions between recent similar studies can be resolved by considering the effects of flexibility and degradation of the elongated micelles on their circulation time and biodistribution.

Optimal biodistribution and prolonged circulation of nanocarriers improve diagnostic and therapeutic effects of enhanced permeability and retention-based nanomedicines. Despite extensive use of Pluronics in polymer-based pharmaceuticals, the influence of different poly(ethylene oxide) (PEO) block length and aggregation state on the biodistribution of the carriers is rather unexplored. In this work, we studied these effects by evaluating the biodistribution of Pluronic unimers and cross-linked micelles with different PEO block size. In vivo biodistribution of ¹¹¹In-radiolabeled Pluronic nanocarriers was investigated in healthy mice using single photon emission computed tomography. All carriers show fast uptake in the organs from the reticuloendothelial system followed by a steady elimination through the hepatobiliary tract and renal filtration. The PEO block length affects the initial renal clearance of the compounds and the overall liver uptake. The aggregation state influences the long-term accumulation of the nanocarriers in the liver. We showed that the circulation time and elimination pathways can be tuned by varying the physicochemical properties of Pluronic copolymers. Our results can be beneficial for the design of future Pluronic-based nanomedicines.

We present an approach which makes it possible to directly determine the bending modulus of single elongated block copolymer micelles. This is done by forming arrays of suspended micelles onto microfabricated substrates and by performing three-point bending flexural tests, using an atomic force microscope, on their suspended portions. By coupling the direct atomic force microscopy measurements with differential scanning calorimetry data, we show that the presence of a crystalline corona strongly increases the modulus of the copolymer elongated micelles. This large increase suggests that crystallites in the corona are larger and more uniformly oriented due to confinement effects. Our findings together with this hypothesis open new interesting avenues for the preparation of core-templated polymer fibres with enhanced mechanical properties.