Design and optimization of cranberry extract loaded bile salt augmented liposomes for targeting of MCP-1/STAT3/VEGF signaling pathway in DMN-intoxicated liver in rats.

Cranberry extract (CBE) is a major source of the antioxidant polyphenolics but suffers from limited bioavailability. The goal of this research was to encapsulate the nutraceutical (CBE), into bile salt augmented liposomes (BSALs) as a promising oral delivery system to potentiate its hepatoprotective impact against dimethylnitrosamine (DMN) induced liver injury in rats. The inclusion of bile salt in the liposomal structure can enhance their stability within the gastrointestinal tract and promote CBE permeability. CBE loaded BSALs formulations were fabricated utilizing a (23) factorial design to explore the impact of phospholipid type (X1), phospholipid amount (X2), and sodium glycocholate (SGC) amount (X3) on BSALs properties, namely; entrapment efficiency percent, (EE%); vesicle size, (VS); polydispersity index; (PDI); zeta potential, (ZP); and release efficiency percent, (RE%). The optimum formulation (F1) exhibited spherical vesicles with EE% of 71.27 ± 0.32%, VS; 148.60 ± 6.46 nm, PDI; 0.38 ± 0.02, ZP; -18.27 ± 0.67 mV and RE%; 61.96 ± 1.07%. Compared to CBE solution, F1 had attenuated DMN-induced hepatic injury, as evidenced by the significant decrease in serum level of ALT, AST, ALP, MDA, and elevation of GSH level, as well as SOD and GPX activities. Furthermore, F1 exhibited an anti-inflammatory character by suppressing TNF-α, MCP-1, and IL-6, as well as downregulation of VEGF-C, STAT-3, and IFN-γ mRNA levels. This study verified that when CBE was integrated into BSALs, F1, its hepatoprotective effect was significantly potentiated to protect the liver against DMN-induced damage. Therefore, F1 could be deliberated as an antioxidant, antiproliferative, and antifibrotic therapy to slow down the progression of hepatic damage.

Novel Intranasal Drug Delivery: Geraniol Charged Polymeric Mixed Micelles for Targeting Cerebral Insult as a Result of Ischaemia/Reperfusion.

Brain damage caused by cerebral ischaemia/reperfusion (I/R) can lead to handicapping. So, the present study aims to evaluate the prophylactic and therapeutic effects of geraniol in the form of intranasal polymeric mixed micelle (PMM) on the central nervous system in cerebral ischaemia/reperfusion (I/R) injury. A 32 factorial design was used to prepare and optimize geraniol PMM to investigate polymer and stabilizer different concentrations on particle size (PS) and percent entrapment efficiency (%EE). F3 possessing the highest desirability value (0.96), with a PS value of 32.46 ± 0.64 nm, EE of 97.85 ± 1.90%, and release efficiency of 59.66 ± 0.64%, was selected for further pharmacological and histopathological studies. In the prophylactic study, animals were classified into a sham-operated group, a positive control group for which I/R was done without treatment, and treated groups that received vehicle (plain micelles), geraniol oil, and geraniol micelles intranasally before and after I/R. In the therapeutic study, treated rats received geraniol oil and micelles after I/R. Evaluation of the effect of geraniol on behavior was done by activity cage and rotarod and the analgesic effect tested by hot plate. Anti-inflammatory activity was assessed by measuring interleukin ß6, cyclooxygenase-2, hydrogen peroxide, and inducible nitric oxide synthase. Histopathogical examination of cerebral cortices was also done to confirm the results of a biochemical assay. Geraniol nanostructured polymeric mixed micelles showed an enhanced neuro-protective effect compared to geraniol oil, confirming that PMM via intranasal route could be an efficient approach for delivering geraniol directly to the brain through crossing the blood-brain barrier.