The Blood Brain Barrier and its Role in Alzheimer's Therapy: An Overview.

BACKGROUND: Alzheimer's disease (AD) is the most frequent age related neurodegenerative disorder. It represents 70% of all dementia. Millions of people have been affected by AD worldwide. It is a complex illness characterized pathologically by accumulation of protein aggregates of amyloid and neurofibrillary tangles containing hyperphosphorylated neuronal tau protein. AD requires drugs that can circumvent the blood-brain barrier (BBB) which is not a simple physical barrier between blood and brain, but acts as an iron curtain, allowing only selective molecules to enter the brain. Unfortunately, this dynamic barrier restricts transport of drugs to the brain; due to which, currently very few drugs are available for AD treatment. OBJECTIVE: The present review focuses mainly on strategies used for administration of drug to the CNS by-passing BBB for the treatment of AD. RESULTS: Many studies have proved to be effective in overcoming BBB and targeting drugs to CNS by using different strategies. Here we have discussed some of the most important drug permeability and drug targeting approaches. CONCLUSION: In conclusion, concentrating solely in development of drug discovery programs is not enough but it is important to maintain balance between the drug discovery and drug delivery systems that are more specific and effective in targeting CNS of AD patients.

In vitro and in vivo evaluation of locust bean gum and chitosan combination as a carrier for buccal drug delivery.

The object of the study was to evaluate locust bean gum and chitosan in ratios of 2:3; 3:2 and 4:1 (F1, F2 and F3) as a mucoadhesive component in buccal tablets and to compare the bioavailability of a propranolol hydrochloride buccal tablet with the oral tablet in healthy human volunteers. Propranolol hydrochloride buccal tablets containing various weight ratios of locust bean gum and chitosan were prepared and coated with 5% w/v ethyl cellulose on one face, and oral tablets containing 10 mg propranolol hydrochloride alone were formulated using a direct compression technique. The strength of mucoadhesion of the tablets was quantified based on the tensile force required to break the adhesive bond between a model membrane (porcine buccal mucosa) and the test polymer. The forces of detachment for the mucoadhesive buccal tablets were 14.61 +/- 0.14, 13.21 +/- 0.13 and 11.71 +/- 0.12. An in vitro study was carried out in pH 6.8 phosphate buffer and the cumulative percentage release of propranolol measured at 10 min intervals for 600 min was found to be 98.31 +/- 0.10, 92.24 +/- 0.41 and 90.18 +/- 0.76 respectively. A bioavailability study was conducted with the prepared formulation in 16 healthy human volunteers to determine the plasma concentration of propranolol at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h. The bioavailability (AUC(0-t*) ng x h/ml) of the buccal propranolol hydrochloride tablets (F1, F2 and F3) and oral tablet (F4) was found to be 2244.18 +/- 210, 3580.69 +/- 460, 3889.19 +/- 290 and 1732 +/- 96 ng x hr/ml respectively. The study indicates that locust bean gum and chitosan in a weight ratio of 2:3 (F1) not only releases the drug unidirectionally from the dosage form, but also gives buccal tablets which are sufficiently mucoadhesive for clinical applications.