Comparative in vitro transportation of pentamidine across the blood-brain barrier using polycaprolactone nanoparticles and phosphatidylcholine liposomes.

Nanoparticles (NPs) have gained importance in addressing drug delivery challenges across biological barriers. Here, we reformulated pentamidine, a drug used to treat Human African Trypanosomiasis (HAT) in polymer based nanoparticles and liposomes and compared their capability to enhance pentamidine penetration across blood brain barrier (BBB). Size, polydispersity index, zeta potential, morphology, pentamidine loading and drug release profiles were determined by various methods. Cytotoxicity was tested against the immortalized mouse brain endothelioma cells over 96 h. Moreover, cells monolayer integrity and transportation ability were examined for 24 h. Pentamidine-loaded polycaprolactone (PCL) nanoparticles had a mean size of 267.58, PDI of 0.25 and zeta potential of -28.1 mV and pentamidine-loaded liposomes had a mean size of 119.61 nm, PDI of 0.25 and zeta potential 11.78. Pentamidine loading was 0.16 µg/mg (w/w) and 0.17 µg/mg (w/w) in PCL NPs and liposomes respectively. PCL nanoparticles and liposomes released 12.13% and 22.21% of pentamidine respectively after 24 h. Liposomes transported 87% of the dose, PCL NPs 66% of the dose and free pentamidine penetration was 63% of the dose. These results suggest that liposomes are comparatively promising nanocarriers for transportation of pentamidine across BBB.

Kenyan purple tea anthocyanins ability to cross the blood brain barrier and reinforce brain antioxidant capacity in mice.

Studies on antioxidants as neuroprotective agents have been hampered by the impermeability of the blood brain barrier (BBB) to many compounds. However, previous studies have shown that a group of tea flavonoids, the catechins, are brain permeable and neuroprotective. Despite this remarkable observation, there exist no data on the bioavailability and pharmacological benefits of tea anthocyanins (ACNs) in the brain tissue. This study investigated the ability of Kenyan purple tea ACNs to cross the BBB and boost the brain antioxidant capacity. Mice were orally administered with purified and characterized Kenyan purple tea ACNs or a combination of Kenyan purple tea ACNs and coenzyme-Q10 at a dose of 200 mg/kg body weight in an experiment that lasted for 15 days. Twenty-four hours post the last dosage of antioxidants, CO2 was used to euthanize the mice after which the brain was excised and used for various biochemical analyses. Brain extracts were analysed by high-performance liquid chromatography for ACN metabolites and spectrophotometry for cellular glutathione (GSH). Kenyan purple tea ACNs significantly (P < 0.05) raised brain GSH levels implying boost in brain antioxidant capacity. However, co-administration of both antioxidants caused a reduction of these beneficial effects implying a negative interaction. Notably, ACN metabolites were detected in brain tissue of ACN-fed mice. Our results constitute the first demonstration that Kenyan purple tea ACNs can cross the BBB reinforcing the brain's antioxidant capacity. Hence, the need to study them as suitable candidates for dietary supplements that could support antioxidant capacity in the brain and have potential to provide neuroprotection in neurodegenerative conditions.