Characterization of four vaccine-related polioviruses including two intertypic type 3/type 2 recombinants associated with aseptic encephalitis

Temperature sensitivity of 4 poliovirus type 3 isolates. (DOC 31 kb

Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates.

Tumor metastasis into the central nervous system (CNS) and lymph nodes (LNs) is a major obstacle for effective therapies. Therapeutic monoclonal antibodies (mAb) have revolutionized tumor treatment; however, their efficacy for treating metastatic tumors-particularly, CNS and LN metastases-is poor due to inefficient penetration into the CNS and LNs following intravenous injection. We recently reported an effective delivery of mAb to the CNS by encapsulating the anti-CD20 mAb rituximab (RTX) within a thin shell of polymer that contains the analogs of choline and acetylcholine receptors. This encapsulated RTX, denoted as n-RTX, eliminated lymphoma cells systemically in a xenografted humanized mouse model using an immunodeficient mouse as a recipient of human hematopoietic stem/progenitor cells and fetal thymus more effectively than native RTX; importantly, n-RTX showed notable anti-tumor effect on CNS metastases which is unable to show by native RTX. As an important step toward future clinical translation of this technology, we further analyzed the properties of n-RTX in immunocompetent animals, rats, and non-human primates (NHPs). Our results show that a single intravenous injection of n-RTX resulted in 10-fold greater levels in the CNS and 2-3-fold greater levels in the LNs of RTX, respectively, than the injection of native RTX in both rats and NHPs. In addition, we demonstrate the enhanced delivery and efficient B-cell depletion in lymphoid organs of NHPs with n-RTX. Moreover, detailed hematological analysis and liver enzyme activity tests indicate n-RTX treatment is safe in NHPs. As this nanocapsule platform can be universally applied to other therapeutic mAbs, it holds great promise for extending mAb therapy to poorly accessible body compartments

Nanomaterials for Delivering Antibiotics in the Therapy of Pneumonia

Bacterial pneumonia is one of the leading causes of death worldwide and exerts a significant burden on health-care resources. Antibiotics have long been used as first-line drugs for the treatment of bacterial pneumonia. However, antibiotic therapy and traditional antibiotic delivery are associated with important challenges, including drug resistance, low bioavailability, and adverse side effects; the existence of physiological barriers further hampers treatment. Fortunately, these limitations may be overcome by the application of nanotechnology, which can facilitate drug delivery while improving drug stability and bioavailability. This review summarizes the challenges facing the treatment of bacterial pneumonia and also highlights the types of nanoparticles that can be used for antibiotic delivery. This review places a special focus on the state-of-the-art in nanomaterial-based approaches to the delivery of antibiotics for the treatment of pneumonia