CNS-targeted glucocorticoid reduces pathology in mouse model of amyotrophic lateral sclerosis.

Background: Hallmarks of CNS inflammation, including microglial and astrocyte activation, are prominent features in post-mortem tissue from amyotrophic lateral sclerosis (ALS) patients and in mice overexpressing mutant superoxide dismutase-1 (SOD1G93A). Administration of non-targeted glucocorticoids does not significantly alter disease progression, but this may reflect poor CNS delivery. Here, we sought to discover whether CNS-targeted, liposomal encapsulated glucocorticoid would inhibit the CNS inflammatory response and reduce motor neuron loss.

Glutathione pegylated liposomal methylprednisolone administration after the early phase of status epilepticus did not modify epileptogenesis in the rat.

It has been reported that glucocorticoids (GCs) can effectively control seizures in pediatric epilepsy syndromes, possibly by inhibition of inflammation. Since inflammation is supposed to be involved in epileptogenesis, we hypothesized that treatment with GCs would reduce brain inflammation and thereby modify epileptogenesis in a rat model for temporal lobe epilepsy, in which epilepsy gradually develops after electrically induced status epilepticus (SE). To prevent the severe adverse effects that are inevitable with long-term GC treatment, we used liposome nanotechnology (G-Technology(®)) to enhance the sustained delivery to the brain.

Pharmacokinetics, brain delivery, and efficacy in brain tumor-bearing mice of glutathione pegylated liposomal doxorubicin (2B3-101).

Brain cancer is a devastating disease affecting many people worldwide. Effective treatment with chemotherapeutics is limited due to the presence of the blood-brain barrier (BBB) that tightly regulates the diffusion of endogenous molecules but also xenobiotics. Glutathione pegylated liposomal doxorubicin (2B3-101) is being developed as a new treatment option for patients with brain cancer.

Enhanced brain delivery of liposomal methylprednisolone improved therapeutic efficacy in a model of neuroinflammation.

Neuroinflammation contributes to a wide range of disorders of the central nervous system (CNS). Of the available anti-inflammatory drugs, only glucocorticoids have shown central efficacy in CNS-related disorders, such as multiple sclerosis (MS). However, their side effects are dose limiting.

bis-Cholesteryl-conjugated phosphorothioate oligodeoxynucleotides are highly selectively taken up by the liver.

We previously modulated, by conjugating a single cholesterol, plasma protein binding and liver cell uptake of a phosphorothioate oligodeoxynucleotide (PS-ODN). In this study, we investigated the biological fate of a PS-ODN, denoted ISIS-9389 (3',5'-bis-cholesteryl-conjugated ISIS 3082), provided with two cholesteryl moieties. After intravenous injection of into rats, [(3)H]ISIS-9389 was cleared from plasma with a half-life of 23.