Design and Development of Lidocaine Microemulsions for Transdermal Delivery.

Topical administration is a preferable choice for local anesthetic delivery. Microemulsions have shown great effectiveness for transdermal transport of lidocaine. However, fabrication of microemulsions containing highly concentrated lidocaine (10%) to provide an extended local anesthetic effect is still a challenge. This study investigated the feasibility of using microemulsions for transdermal delivery of a high dosage of lidocaine (10%). At first, eutectic mixtures by kneading lidocaine with thymol were tailored to form a lipophilic solution, then the mixtures were readily incorporated into the oil phase of microemulsions after addition of proper surfactants and cosurfactants. The physicochemical properties, the skin permeation, local anesthetic efficacy, and the irritation experiment of the developed microemulsions were evaluated. The optimum composition was as follows: 12% of ethyl oleate as oil phase, 28% of the mixed surfactant, and cosurfactant (polyoxyl 15 hydroxystearate and ethanol) and 60% of the aqueous phase. The average particle size was about 13 nm. The transmission electron microscope (TEM) studies revealed almost homogeneous spherical globules without aggregation. The Fourier-transform infrared spectroscopy (FTIR) results highlighted the drugs homogeneously dispersed in the microemulsions. In vitro skin permeation and in vivo anesthesia effect evaluation indicated that microemulsions can enhance and extend the anesthetic effect of lidocaine. The irritable results indicated that the microemulsions had the better biocompatibility and the negligible influence on the dermal. Therefore, incorporating the eutectic mixtures into microemulsions could be proposed as an attractive choice and a promising transdermal delivery strategy for the future topical anesthetic therapy.

Osthole-Loaded Nanoemulsion Enhances Brain Target in the Treatment of Alzheimer's Disease via Intranasal Administration.

Osthole (OST) is a natural coumarin compound that exerts multiple pharmacologic effects. However, the poor water solubility and the low oral absorption of OST limit its clinical application for the treatment of neurologic diseases. A suitable preparation needs to be tailored to evade these unfavourable properties of OST. In this study, an OST nanoemulsion (OST-NE) was fabricated according to the pseudoternary phase diagram method, which was generally used to optimize the prescription in light of the solubility of OST in surfactants and cosurfactants. The final composition of OST-NE was 3.6% of ethyl oleate as oil phase, 11.4% of the surfactant (polyethylene glycol ester of 15-hydroxystearic acid: polyoxyethylene 35 castor oil = 1 : 1), 3% of polyethylene glycol 400 as cosurfactant, and 82% of the aqueous phase. The pharmacokinetic study of OST-NE showed that the brain-targeting coefficient of OST was larger by the nasal route than that by the intravenous route. Moreover, OST-NE inhibited cell death, decreased the apoptosis-related proteins (Bax and caspase-3), and enhanced the activity of antioxidant enzymes (superoxide dismutase and glutathione) in L-glutamate-induced SH-SY5Y cells. OST-NE improved the spatial memory ability, increased the acetylcholine content in the cerebral cortex, and decreased the activity of acetylcholinesterase in the hippocampus of Alzheimer's disease model mice. In conclusion, this study indicates that the bioavailability of OST was improved by using the OST-NE via the nasal route. A low dose of OST-NE maintained the neuroprotective effects of OST, such as inhibiting apoptosis and oxidative stress and regulating the cholinergic system. Therefore, OST-NE can be used as a possible alternative to improve its bioavailability in the prevention and treatment of Alzheimer's disease.