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

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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.

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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

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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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Authors and Affiliations

  1. College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, 32307, USA

    Pinaki R. Desai, Punit P. Shah & Mandip Singh

  2. Dr. Reddys Laboratories, Integrated Product Development, Bachupallyi, Hyderabad, AP, 500090, India

    Ram R. Patlolla

Authors
  1. Pinaki R. Desai
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  2. Punit P. Shah
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  3. Ram R. Patlolla
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  4. Mandip Singh
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Correspondence to Mandip Singh.

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Desai, P.R., Shah, P.P., Patlolla, R.R. et al. Dermal Microdialysis Technique to Evaluate the Trafficking of Surface-Modified Lipid Nanoparticles upon Topical Application. Pharm Res 29, 2587–2600 (2012). https://doi.org/10.1007/s11095-012-0789-2

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  • DOI: https://doi.org/10.1007/s11095-012-0789-2

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