Dermal Microdialysis Technique to Evaluate the Trafficking of Surface-Modified Lipid Nanoparticles upon Topical Application
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.
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 (PGE2) 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.
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 PGE2 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.
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.
KEY WORDScell penetrating peptides dermal pharmacokinetics microdialysis nanoparticles polyarginine peptide
allergic contact dermatitis
cell penetrating peptide
Cxb encapsulated NLCs
Polyarginine-11 (R11) coated CXBN
Polyarginine-11 (R15) coated CXBN
Polyarginine-8 (R8) coated CXBN
TAT coated CXBN
YKA coated CXBN
1,2-dioleoyl-sn-glycero-3-[(N-(5-amino-1-carboxypentyl) imidodiacetic acid) succinyl nickel salt]
nano-structured lipid carrier
trans-acting activator of transcription
ACKNOWLEDGMENTS AND DISCLOSURES
This project was supported by the National Center for Research Resources and the National Institute of Minority Health and Health Disparities of the National Institutes of Health through Grant Number 8 G12 MD007582-28 and 2 G12 RR003020. The authors declare no conflicts.
- 23.Shah PP, Desai PR, Channer D, Singh M. Enhanced skin permeation using polyarginine modified nanostructured lipid carriers. J Control Release. 2012. doi: 10.1016/j.jconrel.2012.05.011.