Studies on pomegranate seed oil enriched galantamine hydrobromide microemulsion: formulation, in vitro antioxidant and neuroprotective potential.

Pomegranate seed oil with its high levels of phenolic compounds is known to exhibit neuroprotective effects. Delivering hydrophilic drugs to the brain is challenging since blood-brain barrier allows only a few lipophilic molecules into the brain, thus posing an additional barrier for drug delivery to the brain in conditions like Alzheimer's. The present study focuses on the preparation of the stable galantamine hydrobromide (GHBr) microemulsion (ME) using pomegranate seed oil (PSO) as an adjuvant. The developed ME was characterized for various physicochemical properties, cytotoxicity, and protective role against Amyloid Beta (1-42) oligomer-induced toxicity in IMR 32 cell line. GHBr and PSO ratio was optimized based on an in-vitro diffusion study and compatibility study using DSC and FTIR. The ME was prepared by the water titration method and optimized using the one variable at a time (OVAT) strategy. Globule size and PDI of GHBr PSO ME were found to be 200.36 ± 0.01 nm, and 0.219 ± 0.011 nm respectively. GHBr PSO ME showed significantly better results in terms of cell line toxicity, antioxidant activity and protective effect against Aß induced cell death. The results obtained showed the potential of using PSO as an effective synergistic agent along with the anti-Alzheimer's drug for the treatment of disease.

Role of Omega-3 Fatty Acids and Butter Oil in Targeting Delivery of Donepezil Hydrochloride Microemulsion to Brain via the Intranasal Route: a Comparative Study.

In order to investigate the possible role of butter oil (BO) and omega-3 fatty acids-rich fish oil (O3FO) in the delivery of donepezil hydrochloride microemulsion (DH-ME) to the brain via intranasal route, the present study was conducted. DH:BO and DH:O3FO binary mixtures (9:1 to 1:9) were prepared by simple physical mixing and subjected to in vitro diffusion study. Ratios of DH:BO and DH:O3FO, which showed the highest diffusion, were selected for further development of microemulsion (ME). Globule sizes of DH-BO-ME and DH-O3FO-ME were found to be 87.66 ± 5.23 nm and 88.59 ± 8.23 nm, respectively. Nasal histopathological study and in vitro cytotoxicity study revealed the safety of the formulation. Higher percentage of nasal diffusion was found with DH-BO-ME (71.22 ± 1.21%) and DH-O3FO-ME (62.16 ± 1.23%) in comparison to DH-ME (59.69 ± 1.74%) and DH solution (55.01 ± 1.19%), which was further supported by in vitro cell permeability study. After intranasal administration, %bioavailability of drug in the rat brain (Sprague-Dawley rats)(on the basis of DH-ME IV) was higher with DH-BO-ME (313.59 ± 12.98%) and DH-O3FO-ME (361.73 ± 15.15%) in comparison to DH-ME (168.62 ± 6.60%) and DH solution (8.960 ± 0.23%). The results of ex vivo diffusion study and in vivo pharmacokinetic study suggested that BO and O3FO helped in enhancing the nasal permeability and the brain uptake of drug when administered intranasally.