Liposomal temozolomide drug delivery using convection enhanced delivery.

Even though some progress in diagnosis and treatment has been made over the years, there is still no definitive treatment available for Glioblastoma multiforme (GBM). Convection-enhanced delivery (CED), a continuous infusion-mediated pressure gradient via intracranial catheters, studied in clinical trials, enables in situ drug concentrations several orders of magnitude greater than those achieved by systemic administration. We hypothesized that the currently limited efficacy of CED could be enhanced by a liposomal formulation, thus achieving enhanced drug localization to the tumor site with minimal toxicity. We hereby describe a novel approach for treating GBM by CED of liposomes containing the known chemotherapeutic agent, temozolomide (TMZ). A new technique for encapsulating TMZ in hydrophilic (PEGylated) liposomes, characterized by nano-size (121nm), low polydispersity index (<0.13) and with near-neutral charge (-ʒ,0.2mV), has been developed. Co-infusion of PEGylated Gd-DTPA liposomes and TMZ-liposomes by CED in GBM bearing rats, resulted in enhanced tumor detection with longer residence time than free Gd-DTPA. Treatment of GBM-bearing rats with either TMZ solution or TMZ-liposomes resulted in greater tumor inhibition and significantly higher survival. However, the longer survival and smaller tumor volumes exhibited by TMZ liposomal treatment in comparison to TMZ in solution were insignificant (p<0.053); and only significantly lower edema volumes were observed. Thus, there are no clear-cut advantages to use a liposomal delivery system of TMZ via CED over a drug solution.

A novel herbal treatment reduces depressive-like behaviors and increases BDNF levels in the brain of stressed mice.

AIMS: Depression is a chronic, recurring and potentially life-threatening illness. Current treatments for depression are characterized by a low success rate and associated with a wide variety of side effects. The aim of the present study was to evaluate the behavioral and biological anti-depressant effects of a novel herbal treatment (NHT), as well as to assess its potential side effects, in comparison to treatment with the selective serotonin reuptake inhibitor escitalopram. MAIN METHODS: Depressive-like behavior was evaluated using the forced swim test (FST) and the tail suspension test (TST). Sexual behavior was evaluated following treatment by measuring latency before first mount and number of total mounts. Brain derived neurotrophic factor (BDNF) levels were evaluated using enzyme-linked immunosorbent assay. Serotonin transporter (SERT) levels in the pre-frontal cortex (PFC) and hypothalamus were evaluated using high affinity binding assay. KEY FINDINGS: (1) The NHT reduced depressive-like behavior in the FST and TST; (2) BDNF levels in the PFC of mice treated both with the NHT and escitalopram were increased; (3) SERT levels in the hypothalamus were significantly higher in the NHT group, in comparison to escitalopram and the control groups, and significantly lower in the PFC of the NHT group in comparison to the escitalopram group; and (4) the NHT led to less sexual dysfunction, compared to treatment with escitalopram. SIGNIFICANCE: Our NHT has the potential of being highly efficacious in treating depression in humans, while causing minimal to no influence on sexual function.