Application of Nanoemulsion in Transdermal Drug Delivery

Nanoemulsion has a particle size between 20-200nm, and its particle size is more suitable for drug loading and targeting. Nanoemulsion as a drug carrier has the following characteristics: 1. Nanoemulsion has the characteristics of solubilization and sensitization; 2. Nanoemulsion is simple to prepare, good physical stability, etc., and can be sterilized; 3. Nanoemulsion can simultaneously contain different Fat-soluble drugs, improve the stability of some unstable drugs; 4. Nanoemulsions increase the bioavailability of macromolecular drugs; 5. Nanoemulsions can improve the solubility of insoluble drugs; 6. Nanoemulsions have low viscosity; 7. Nanoemulsions The diameter is small and uniform, which can improve the dispersion of the encapsulated drug, and protect the easily hydrolyzed drug into a water-in-oil nanoemulsion; 8. The nanoemulsion has a slow-release effect.

The mechanism of nanoemulsion to promote drug absorption

1. Increase Stratum Corneum Cell Membrane Fluidity

After the nanoemulsion is in contact with the stratum corneum, the surfactant components penetrate into the stratum corneum cell membrane, enhancing the fluidity of the cell membrane and increasing the permeability. At the same time, the hydrophilic area of the nanoemulsion enables strong hydration of the stratum corneum and further enhances the permeability. The transdermal penetration rate of hydrocortisone nanoemulsion is 338 times higher than that of hydrocortisone saturated solution.

2. Solubilize Drugs and Increase Drug Loading

The poorly soluble drugs are dissolved in the oil phase to prepare O/W nanoemulsion, and the drug loading is greatly increased. The lipophilic drug estradiol O/W nanoemulsion is compared with the pH 7.4 phosphate buffered saline (PBS) saturated solution of estradiol, the nanoemulsion can solubilize the drug by 1,400 to 4,500 times, but the increase in viscosity reduces the penetration of the drug Coefficient, the total skin penetration rate is significantly increased, which is 200-700 times that of saturated solution, and the time lag is significantly shortened from 10-20h to 1h. Using isostearate as the oil phase, polyoxyethylene 8-caprylic acid glyceride as the surfactant, and polyglycerol-6-isostearate as the co-surfactant to prepare lipophilic drugs, lidocaine and hydrophilic drugs The permeation rate of prilocaine hydrochloride nanoemulsion in vitro shows that the permeation rate of saturated lidocaine nanoemulsion is 4 times higher than that of ordinary O/W nanoemulsion, and the permeation rate of saturated prilocaine hydrochloride nanoemulsion is higher than that of the corresponding hydrogel. But the nanoemulsion skin permeability coefficient is lower than the corresponding emulsion and hydrogel, indicating that nanoemulsion increases the drug skin permeability rate mainly to increase the nanoemulsion drug loading and increase the skin surface concentration gradient of the drug.

3. Enhance the Transdermal Absorption of Macromolecular Drugs

Ionic and water-soluble macromolecular drugs are difficult to pass through the lipid-rich stratum corneum, and the penetration rate of the epidermis is very low. Skin adnexities such as hair follicles, sebaceous glands and sweat glands are the main channels for such drugs to be absorbed through the skin. The particle size of the nanoemulsion is similar to that of the hair follicle. The W/О type nanoemulsion is prepared by using oil compatible with hair follicle sebum as the continuous phase, which can promote the penetration of hydrophilic drugs into the skin. Using olive oil as the oil phase and Span 80/Polysorbate 80 as surfactants, the macromolecular hydrophilic drug inulin (molecular weight is about 5000) is made into W/O nanoemulsion. The permeation rate of inulin mouse skin is inversely proportional to the hydrophilic lipophilic balance (HLB) of the surfactant, that is, the lower the surfactant HLB, the stronger the lipophilicity, the better the compatibility of nanoemulsion and sebum, the better the drug permeability The higher the overrate. The skins of isolated mice, nude mice and rats were used for the nanoemulsion transdermal test. There was no significant difference in the measurement results, that is, the thickness of the stratum corneum and the type of hair follicles had no significant effect on the transdermal penetration of inulin. Therefore, the destructive effect of the surfactant in the nanoemulsion on the skin stratum corneum structure has little effect on the penetration rate of inulin, while the nanoemulsion structure and sebum compatibility are the decisive factors for the penetration of macromolecular inulin through the skin.

4. Slow Release, Reduce Drug Irritation

Nanoemulsion transdermal administration can not only increase the penetration rate of the drug, but also delay the release of the drug. The Franz diffusion cell was used to study the penciclovir nanoemulsion in vivo and in vitro permeation ability. Compared with the commercially available Futan cream, the penciclovir content in the epidermis and dermis of the cream group showed a significant decrease after 2 hours of administration. It is lower than the minimum detection concentration; and the skin after nanoemulsion has a higher drug content within 12h, and still has a certain concentration at 24h, indicating that penciclovir nanoemulsion has a certain slow-release effect. Nanoemulsions can improve drug irritation and adverse reactions. Using oleic acid as the oil phase, polysorbate 80 as the surfactant, and propylene glycol as the co-surfactant, triptolide nanoemulsion was prepared, and the Franz diffusion cell method was used to evaluate the transdermal performance. The skin permeability of nanoemulsion is better than that of aqueous solution, and the diffusion process conforms to Fick’s first diffusion law, and no obvious skin irritation is seen, while the aqueous solution group shows obvious skin irritation.