Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa.

Intranasal drug delivery is a promising approach for the delivery of drugs to the CNS, but too heterogenous, unprecise delivery methods without standardization decrease the quality of many studies in rodents. Thus, the lack of a precise and region-specific application technique for mice is a major drawback. In this study, a previously developed catheter-based refined technique was validated against the conventional pipette-based method and used to specifically reach the olfactory or the respiratory nasal regions. This study successfully demonstrated region-specific administration at the olfactory mucosa resulting in over 20% of the administered fluorescein dose in the olfactory bulbs, and no peripheral bioactivity of insulin detemir and Fc-dependent uptake of two murine IgG1 (11C7 and P3X) along the olfactory pathway to cortex and hippocampus. An scFv of 11C7 showed hardly any uptake to the CNS. Elimination was dependent on the presence of the IgG's antigen. In summary, it was successfully demonstrated that region-specific intranasal administration via the olfactory region resulted in improved brain targeting and reduced peripheral targeting in mice. The data are discussed with regard to their clinical potential.

Elevated levels of oxidized low-density lipoprotein and of catalase activity in follicular fluid of obese women.

The intrafollicular levels of oxidized low-density lipoprotein (oxLDL) and of enzyme antioxidants might contribute to reproductive disorders in obese and infertile women. Relevant data are missing. Eighty-four patients were grouped according to obese versus non-obese status and whether they had polycystic ovary syndrome (PCOS). The concentrations of oxLDL and the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR) in the serum and follicular fluid were measured. Obese women with and without PCOS had significantly greater amounts of oxLDL in the follicular fluid as compared with non-obese women. The level of oxLDL in the follicular fluid was 1000 times lower than in serum. Obese women with and without PCOS had significantly higher catalase activity in the follicular fluid as compared with non-obese women. No differences were found for the SOD activity in the follicular fluid. The GPx and GR activities were up-regulated in obese patients without and with PCOS, yet not in respect to each serum and follicular fluid sample. We conclude that elevated levels of oxLDL in the follicular fluid of obese women are associated with higher catalase activity; both parameters are independent of PCOS. The levels of oxLDL and catalase activity appear to indicate different degrees of oxidative stress.