Tittle: Praparation and Brain delivery property of Polymersomes conjugated with OX26

摘要

In this paper, a novel drug carrier for brain delivery, mouse-anti-rat monoclonal antibody OX26 was conjugated with poly (ethyleneglycol)-poly(-caprolactone) (PEG-PCL) polymersomes (OX26-PSs), was developed and its effects were evaluated. The diblock copolymers of methoxy-PEG-PCL and maleimide-PEG-PCL were synthesized by ring opening polymerization of-caprolactone initiated by methoxy-PEG and maleimide-PEG, respectively, which were applied to prepare polymersomes (PSs) by a solvent injection method. OX26 was thiolated and conjugated to the polymersomes' surface through the maleimide function located at the distal end of PEG surrounding the PSs' surface. Transmission electron micrograph (TEM) and dynamic light scattering (DLS) results showed that OX26-PSs had a round and regular shape with a mean diameter around 100nm. Coupling of OX26 with PSs was confirmed by the existence of gold-labeled OX26-PSs under TEM and X-ray photoelectron spectroscopy (XPS) test. The surface OX26 densities were obtained from Elisa. The average number of OX26 conjugated per PSs was 34.2, 91.8, 156.3 with a Maleimide-PEG-PCL/MPEG-PCL weight ratio of 1:20, 1:10 and 1:5, respectively. The result of brain delivery in rats proved that the increase of surface OX26 density of OX26-PSs decreased blood AUC. The optimized OX26 number conjugated per polymersome was 34, which can acquire the greatest BBB permeability surface area product (PS) and percentage of injected dose per gram brain (% ID/g brain) by 3.44-fold and 2.62-fold compared with those of PSs, respectively. After a dose of 50mg/kg OX2634-PSs or PSs injection in rats tail vein, fluorescent microscopy of brain coronal sections showed a higher accumulation of OX2634-PSs in the cerebral cortex, lateral ventricle, third ventricle and periventricular region than that of PSs. The results indicate that OX2634-PSs is a promising carrier for brain delivery.