\[Abstract\]ObjectiveTo investigate the microneedle technique in enhancement of transdermal nanoparticle delivery and the distribution of poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles in the skin and the transdermal microconduits. MethodsDouble fluorescent PLGA nanoparticles were used to show the transdermal transport process.Franz diffusion cell was used for the transdermal study.The nanoparticle suspension was added to the donor chamber.The hairless mouse skin in the microneedle group was treated by microneedle technique and that in the control group was not treated.Penetration of nanoparticles was visualized by confocal laser scanning microscopy (CLSM).Distribution of nanoparticle diameter was quantified by HPLC.ResultsThe CLSM images revealed that the nanoparticles were delivered into the microconduits created by microneedles and entered the epidermis and the dermis.The quantitative results showed that no nanoparticles reached the receptor compartment 48 h after addition of the nanoparticles in both groups.In microneedle group the nanoparticle amount was 125.99 μg/cm2 in the epidermis and 55.31 μg/cm2 in the dermis,with the total amount in the skin being 181.30 μg/cm2；in the the control group ,the nanoparticle amount was 42.15 μg/cm2 in the epidermis and 32.76 μg/cm2 in the dermis,with the total amount in the skin being 74.91 μg/cm2.Microneedle technique significantly increased the amount of nanoparticles entering the skin (P<0.01),and the amount in the epidermis was significantly more than that in the dermis (P<0.01).ConclusionOur results suggest that microneedles can enhance the intradermal PLGA nanoparticle delivery,and the nanoparticles deposit in the skin to achieve sustainable drug release,which is beneficial for topical drug administration.