Brain delivery of olanzapine by intranasal administration of transfersomal vesicles

Abstract

The aim of this study was to investigate the presence of a possible direct correlation between vesicle elasticity and the amount of drug reaching the brain intranasally. Therefore, transfersomes were developed using phosphatidylcholine (PC) as the lipid matrix and sodium deoxycholate (SDC), Span® 60, Cremophor® EL, Brij® 58, and Brij® 72 as surfactants. The influence of the type of surfactant and PC-to-surfactant ratio on vesicle morphology, size, membrane elasticity, drug entrapment, and in vitro drug release was studied. The prepared transfersomes were mainly spherical in shape, with diameters ranging from 310 to 885 nm. Transfersomes containing SDC and Span 60 with optimum lipid-to-surfactant molar ratio showed suitable diameters (410 and 380 nm, respectively) and deformability indices (17.68 and 20.76 mL/sec, respectively). Values for absolute drug bioavailability in rat plasma for transfersomes containing SDC and those containing Span 60 were 24.75 and 51.35%, whereas AUC(0-360 min) values in rat brain were 22,334.6 and 36,486.3 ng/mL/min, respectively. The present study revealed that the deformability index is a parameter having a direct relation with the amount of the drug delivered to the brain by the nasal route.

Investigating the potential of employing bilosomes as a novel vesicular carrier for transdermal delivery of tenoxicam

“…For drug loaded bilosomes, the characteristic peak of TX completely disappeared which probably signify that TX was either entrapped inside the bilosomes (Salama et al, 2012;Manne et al, 2014) or completely transformed from crystalline form to molecular state in surfactant mixture. Nasr et al (2008) reported that the absence of drug's crystalline melting peak after encapsulation might also indicate the presence of strong interaction between the surfactant bilayers of the vesicles and the entrapped drug.…”

Trans-nasal zolmitriptan novasomes: in-vitro preparation, optimization and in-vivo evaluation of brain targeting efficiency

“…Moreover, the AUC (0-1) and MRT (0)(1) in the brain after I.N administration of 99m Tc-R7 were significantly higher value compared to I.V administration of 99m Tc-ZT solution (23.28 and 0.89 h%/g) and (36.38 and 9.35 h), respectively (p50.05). This could be explained by the high capability of the lipid nanovesicles to permeate the nasal membrane (Salama et al, 2012;Abdelrahman et al, 2015). This suggests that the nasal route is considered as preferential route for brain targeting than I.V.…”

“…The higher MRT value of 99m Tc-R7 after I.N administration confirms the ability of the novasomes formulation to prolong and control the rate of ZT release over an extended period of time. Lipid nanovesicles have been demonstrated to have good permeability characteristics that enhance nasal penetration of many drugs through disrupting the mucosal membrane, hence increase absorption of drugs (Salama et al, 2012). Intranasal novasomes delivery enhanced ZT delivery to the brain through the olfactory pathway in which it travels from the nasal cavity to brain tissue (Illum, 2000).…”

Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies

“…The preparations were administered at the openings of the nostrils (Abd-Elal et al, 2016) using micropipette (200 ml) fixed with low density polyethylene tube having 0.1 mm internal diameter at the delivery site. The procedure was performed gently, allowing the animals to inhale all the preparation (Salama et al, 2012). For I.V administration, 99m Tc-PM7 was injected through the tail vein of Group C mice.…”

“…Samples of pure drug, components (Pluronic Õ P123 and Pluronic Õ L121) and drug-loaded PM (PM7) were heated in an aluminum pan at a rate of 5 C/min in an atmosphere of nitrogen to 400 C and the thermograms were recorded (Salama et al, 2012).…”