Study Of Combination Strategies Of Vesicles And Physical Enhancing Technology For Transdermal Drug Delivery

The Aim of this paper was to improve the permeation rate of model drugs (insulin and podophyllotoxin) in vitro by a combination stratege of vesicles, microneedles array and iontophoresis.Firstly, the main factors which affected the enhancement ability of microneedles for drug transdermal delivery were studied, and the in vitro permeation experiment with microneedles array was established. The insulin-loaded vesicles (ILVs) with different droplet size and different zeta potentials were prepared. The permeation rates of insulin from various ILVs were studied with the enhancement of microneedles array, iontophoresis, and microneedls array combined with iontophoresis. The influence of diameters and zeta potentials of ILVs on permeation ability was discussed.The main results of this study are as follows:(1) The configuration of microneedles and the pre-treating time of microneedles on skin could significantly affect the permeation ability of drug though skin. Among the three types of microneedles studied, the lanciform microneedles resulted in the highest permeation rate of podophyllotoxin (12.63±0.74μg/cm~2/h), then the trapeziform microneedles (10.10±0.61μg/cm~2/h), and the triangular microneedles resulted the lowest permeation rate (5.35±0.39μg/cm~2/h). During the pre-treating time of microneedles on skin, ranging from 1 minute to 3 minute, the permeation rate of podophyllotoxin increased as the pre-treating time grew. The configuration of microneedles also affected the amount of drug left in skin at the end of permeation experiment, while the pre-treating time didn't.(2) Three ILVs with different droplet size: 91.02±8.6 nm,134.0±3.7 nm, 175.9±6.1 nm and three ILVs with different zeta potential: +27.85±3.3 mV,-50.5±3.5 mV,-25.3±2.7 mV were prepared. When microneedles array was used to improve the permeation ability of ILVs, the highest permeation rate of 24.50±1.37μg/cm~2/h of insulin from ILVs with the smallest diameters was obtained. However, the permeation rate showed no linear relation to droplet size. With regard to ILVs with the negative charge, the permeation rate decreased with the increase with the absolute value of charge. The ILVs with positive charges had higher permeation rate of 0.19±0.0096μg/cm~2/h than those with negative charges. (3) The permeation studies of ILVs showed that the combination of microneedles array with iontophoresis could resulted in the highest permeation rate of 106.99±2.78μg/cm~2/h, which was 343-724 times high of those obtained from passive diffusion, 92-134 times high of those aroused by iontophoresis, and 3-8 times high of those aroused by microneedles.The results indicate that the combination of microneedles with iontophoresis and vesicles could obtain a high permeation rate of insulin through skin. It might be prospective method to the development of novel dosage of insulin.