Hydrophilic drug-loaded PLGA nanoparticles for transdermal delivery

Transdermal delivery has been widely studied since it can avoid the effect of first-pass hepatic metabolism and deliver therapeutic agents as systemic or local administration for long period of time. In this study, procaine hydrochloride-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles for transdermal delivery were prepared using a combination of an antisolvent diffusion method with preferential solvation. The physicochemical characteristics and skin permeability were studied. Mean volume diameter of prepared nanoparticles was 99.4 ± 0.8 nm. They were “soft particles” and have negatively charged polyelectrolyte layer on the surface. Ex vivo experiment was carried out using the skin of male Sprague–Dawley rat with Franz diffusion cells. Compared to procaine hydrochloride free molecules, a higher amount of procaine hydrochloride was delivered through rat skin when procaine hydrochloride was loaded in nanoparticles. Moreover, a solution mixture of ethanol and isopropyl myristate, which were used as transdermal enhancers, improved skin permeability of the nanoparticles. In vivo experiment was carried out using male Sprague–Dawley rats aging 8 weeks. Samples were administered on rat abdominal skin (2.5 cm × 2.5 cm). After 9 h, drug concentrations of the skin and muscle under the area of sample administration were measured by using HPLC. Skin accumulation of the drug was increased when drug was included into PLGA nanoparticles, and muscle accumulation was increased by using transdermal enhancer. These results indicate that the nanoparticles that were prepared using a combination of an antisolvent diffusion method with preferential solvation were useful for transdermal delivery.