Binary ethosomes-based transdermal patches assisted by metal microneedles significantly improve the bioavailability of carvedilol

This study aimed to develop a strategy combining binary ethsomes (BES) and microneedles (MNs) to improve the bioavailability of drugs that are poorly bioavailable by oral administration, such as carvedilol (CL). The formula of BES was optimized by Box-Benhnken Designes from four aspects: particle size, zeta potential, encapsulation efficiency and cumulative release in vitro. The optimized BES was then mixed with polyvinylpyrrolidone and sprayed onto the silk fibroin matrix by electrospray to obtain transdermal drug delivery patches (TDDP). In vitro skin penetration test showed that, TDDP has much better transdermal drug release performance compared with free drugs, and MNs-assisted TDDP (MNs-TDDP) can deliver more drugs to the receiving chamber. In vivo studies indicate that MNs-TDDP can significantly reduce the fluctuation of CL concentration in plasma and increase serum level of NO, thereby lower blood pressure for a longer time. These results suggest that the bioavailability of CL can be greatly improved via administration of MNs-TDDP, compared with the oral route. Considering its advantages of non-invasiveness, convenience and good biosafety, MNs-TDDP has a promising prospect in improving the bioavailability of drugs for treating chronic diseases such as hypertension.