Dermal microdialysis technique to evaluate the trafficking of surface-modified lipid nanoparticles upon topical application.

PURPOSE: To evaluate the skin pharmacokinetics and tissue distribution of cell penetrating peptides (CPP) modified nano-structured lipid carrier (NLC) using an in vivo dermal microdialysis (MD) technique.

METHODS

Celecoxib (Cxb) encapsulated NLCs (CXBN), CPP modified CXBN (CXBN-CPP) and Cxb-Solution (CXBS) formulations were prepared and tested for in vitro skin distribution. MD was used to assess pharmacokinetic parameters of Cxb after topical application of Cxb formulations. The effect of pre-treatment with Cxb formulations was evaluated for expression of prostaglandin-E2 (PGE(2)) and Interleukin-6 (IL-6) after exposure of xylene using MD. Allergic contact dermatitis (ACD) model was used to confirm in vivo therapeutic response of Cxb formulations.

RESULTS

The cumulative permeation of Cxb in MD dialysate after 24 h for CXBN-CPP was significantly higher (p < 0.001) than CXBN and CXBS. Further, pre-treatment with CXBN-CPP significantly inhibited PGE(2) and IL-6 expression compared to CXBS and CXBN (p < 0.001). In ACD model, CXBN-CPP showed significant reduction (p < 0.001) in ear thickness compared to controls.

CONCLUSIONS

Surface modification of NLC with CPPs can enhance the skin permeation of Cxb and MD can be used to investigate pharmacokinetics of Cxb nanoparticles in the skin.