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Pharmaceutical Research

, Volume 29, Issue 9, pp 2587–2600 | Cite as

Dermal Microdialysis Technique to Evaluate the Trafficking of Surface-Modified Lipid Nanoparticles upon Topical Application

  • Pinaki R. Desai
  • Punit P. Shah
  • Ram R. Patlolla
  • Mandip Singh
Research Paper

ABSTRACT

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 (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.

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 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.

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.

KEY WORDS

cell penetrating peptides dermal pharmacokinetics microdialysis nanoparticles polyarginine peptide 

ABBREVIATIONS

ACD

allergic contact dermatitis

CPP

cell penetrating peptide

Cxb

Celecoxib

CXBN

Cxb encapsulated NLCs

CXBN-R11

Polyarginine-11 (R11) coated CXBN

CXBN-R15

Polyarginine-11 (R15) coated CXBN

CXBN-R8

Polyarginine-8 (R8) coated CXBN

CXBN-TAT

TAT coated CXBN

CXBN-YKA

YKA coated CXBN

CXBS

Celecoxib-solution

DOGS-NTA-Ni

1,2-dioleoyl-sn-glycero-3-[(N-(5-amino-1-carboxypentyl) imidodiacetic acid) succinyl nickel salt]

IL-6

interleukin-6

MD

microdialysis

NLC

nano-structured lipid carrier

PGE2

prostaglandin E2

TAT

trans-acting activator of transcription

Notes

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.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Pinaki R. Desai
    • 1
  • Punit P. Shah
    • 1
  • Ram R. Patlolla
    • 2
  • Mandip Singh
    • 1
  1. 1.College of Pharmacy and Pharmaceutical SciencesFlorida A&M UniversityTallahasseeUSA
  2. 2.Dr. Reddys LaboratoriesIntegrated Product DevelopmentHyderabadIndia

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