sorbitan-monooleate and trilaurin

The limited brain delivery of carbamezapine (CBZ) presents a major hurdle in the successful epilepsy treatment. The potential of carbamezapine-loaded nanostructured lipid carriers (CBZ-NLCs) for improved brain delivery is investigated in the current study. CBZ-NLCs were prepared by using binary mixture of trilaurin and oleic acid as a lipid core stabilized with Poloxamer 188, Tween 80 and Span 80. CBZ-NLCs were evaluated for physicochemical properties, in vitro release, in vivo brain kinetics, anticonvulsant and anxiolytic activities. The optimized CBZ-NLCs demonstrated nanometric particle size (97.7 nm), surface charge of -22 mV and high drug incorporation (85%). CBZ-NLCs displayed biphasic release pattern with initial fast followed by sustained drug release. CBZ-NLCs significantly enhanced the AUC of CBZ (520.4 µg·h/mL) in brain compared with CBZ dispersion (244.9 µg·h/mL). In vivo anticonvulsant activity of CBZ-NLCs in PTZ-induced seizure model showed a significant increase in the onset time (143.0 sec) and reduction in duration (17.2 sec) of tonic-clonic seizures compared with CBZ dispersion (75.4 and 37.2 sec). The anxiolytic activity in light-dark box and elevated-plus maze models also demonstrated superiority of CBZ-NLCs to CBZ dispersion. From the results, CBZ-NLCs presents a promising strategy to improve brain delivery and therapeutic outcomes of CBZ in epilepsy.

Topics: Animals; Anti-Anxiety Agents; Anticonvulsants; Behavior, Animal; Brain; Carbamazepine; Drug Carriers; Drug Liberation; Hexoses; Lipids; Male; Nanostructures; Oleic Acid; Particle Size; Poloxamer; Polysorbates; Rats; Seizures; Surface Properties; Triglycerides

Cyclosporin A (CsA) is a widely used anti-inflammatory agent for the management of dry eye disease, and is available commercially as ophthalmic emulsion formulation (RESTASIS(®)). For increasing efficacy, and for reducing local toxicity including irritation to eyes, CsA nanosphere (CsA-NS) formulation was prepared and evaluated, in this work. CsA-NS formulation was prepared in a pre-concentrate form, which is a homogeneous solution of a CsA in a mixture of surfactants, lipids and solvents and provides nanosphere dispersion when added to aqueous medium. CsA-NS formulation was characterized and adjusted for particle size, pH, and osmolarity, suitable for ophthalmic administration. Thereafter, CsA-NS formulation was evaluated for parameters like irritation to eyes and penetrability of CsA in the rabbit eyes. Results obtained demonstrated that proposed CsA-NS formulation causes less irritation in rabbit eyes, with nearly same CsA penetration in the rabbit eyes in comparison to marketed emulsion formulation.

Topics: Administration, Ophthalmic; Animals; Anti-Inflammatory Agents; Cyclosporine; Eye; Glycerol; Hexoses; Lecithins; Nanospheres; Pharmaceutical Vehicles; Polysorbates; Propylene Glycol; Rabbits; Solvents; Surface-Active Agents; Triglycerides