Dermal microdialysis technique to evaluate the trafficking of surface-modified lipid nanoparticles upon topical application.
OBJECTIVE
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.
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida 32307, USA.
Pinaki R
PR
Desai
Punit P
PP
Shah
Ram R
RR
Patlolla
Mandip
M
Singh
D000818:Animals; D000068579:Celecoxib; D008055:Lipids / Q000008:administration & dosage*; D017551:Microdialysis / Q000379:methods*; D053758:Nanoparticles; D011720:Pyrazoles / Q000493:pharmacokinetics; D051381:Rats; D054772:Rats, Hairless; D013449:Sulfonamides / Q000493:pharmacokinetics; D013499:Surface Properties
D008055:Lipids; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib