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Structure-Skin Permeability Relationship of Dendrimers

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ABSTRACT

Purpose

To investigate skin penetration of poly (amidoamine) (PAMAM) dendrimers as a function of surface charge and molecular weight in presence and absence of iontophoresis.

Methods

Dendrimers were labeled with fluoroisothiocynate (FITC); skin penetration of dendrimers was studied using excised porcine skin in-vitro. Skin penetration of FITC-labeled dendrimers was quantified using confocal laser scanning microscope (CLSM). G2-G6 NH2, G3.5-COOH and G4-OH dendrimers were used.

Results

Cationic dendrimers showed higher skin penetration than neutral and anionic dendrimers. Skin penetration of cationic dendrimer increased linearly with increase in treatment time. Iontophoresis enhanced skin penetration of cationic and neutral dendrimers. Increase in current strength and current duration increased skin transport of dendrimers. Passive and iontophoretic skin penetration of cationic dendrimers was inversely related to their molecular weight. Dendrimer penetrated the skin through intercellular lipids and hair follicles. With iontophoresis, dendrimer was also found in localized skin regions.

Conclusions

The study demonstrates that the physicochemical properties of dendrimers influence their skin transport. Findings can be used to design dendrimer-based nanocarriers for drug delivery to skin.

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ACKNOWLEDGMENTS

We thank Dr. Kelly Bruns and Mr. Adam Rhody, Meat Science Department, SDSU for providing porcine skin.This work was supported by South Dakota Governor Round’s 2010 individual research seed grant and Department of Pharmaceutical Sciences, South Dakota State University.

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Author notes

  1. Venkata Vamsi Venuganti

    Present address: Pharmacy Division Birla Institute of Technology and Science, Pilani - Hyderabad Campus Jawahar Nagar Shameerpet Mandal, Hyderabad, 500078, Andhra Pradesh, India

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, South Dakota State University, Brookings, South Dakota, 57007, USA

    Preety Sahdev, Xiangming Guan & Omathanu Perumal

  2. Department of Biology and Microbiology, South Dakota State University, Brookings, South Dakota, 57007, USA

    Michael Hildreth

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  1. Venkata Vamsi Venuganti
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Corresponding author

Correspondence to Omathanu Perumal.

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Fig. S1

Representative 1H-NMR spectra of G4-NH2, free FITC and G4-NH2-FITC conjugate. Dotted line corresponds to aromatic protons of FITC (6 to 8 ppm), and solid circle corresponds to aliphatic protons in the dendrimer (2 to 4 ppm). (DOCX 158 kb)

Fig. S2

Representative UV-Visible absorbance spectra of G4-NH2dendrimer-FITC conjugate, free FITC and free dendrimer. The λmax for free FITC was495 nm, while the λmax shifted to 500 nm for G4-NH2dendrimer-FITC conjugate. (DOCX 13 kb)

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Venuganti, V.V., Sahdev, P., Hildreth, M. et al. Structure-Skin Permeability Relationship of Dendrimers. Pharm Res 28, 2246–2260 (2011). https://doi.org/10.1007/s11095-011-0455-0

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  • DOI: https://doi.org/10.1007/s11095-011-0455-0

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