Effect of Size, Surface Charge, and Hydrophobicity of Poly(amidoamine) Dendrimers on Their Skin Penetration

The barrier functions of the stratum corneum and the epidermal layers present a tremendous challenge in achieving effective transdermal delivery of drug molecules. Although a few reports have shown that poly(amidoamine) (PAMAM) dendrimers are effective skin-penetration enhancers, little is known reg...

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Bibliographic Details
Published in:Biomacromolecules 2012-07, Vol.13 (7), p.2154-2162
Main Authors: Yang, Yang, Sunoqrot, Suhair, Stowell, Chelsea, Ji, Jingli, Lee, Chan-Woo, Kim, Jin Woong, Khan, Seema A, Hong, Seungpyo
Format: Article
Language:English
Subjects:
Acetylation
Animals
Applied sciences
Biological and medical sciences
Dendrimers - chemistry
Dendrimers - metabolism
Exact sciences and technology
Female
Fluorescent Dyes - chemistry
Fluorescent Dyes - metabolism
General pharmacology
Hydrophobic and Hydrophilic Interactions
Medical sciences
Microscopy, Confocal
Miscellaneous
Organic polymers
Particle Size
Permeability
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Physicochemistry of polymers
Polyamines - chemistry
Polyamines - metabolism
Properties and characterization
Rhodamines - chemistry
Rhodamines - metabolism
Skin - metabolism
Surface Properties
Sus scrofa
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Summary:The barrier functions of the stratum corneum and the epidermal layers present a tremendous challenge in achieving effective transdermal delivery of drug molecules. Although a few reports have shown that poly(amidoamine) (PAMAM) dendrimers are effective skin-penetration enhancers, little is known regarding the fundamental mechanisms behind the dendrimer–skin interactions. In this Article, we have performed a systematic study to better elucidate how dendrimers interact with skin layers depending on their size and surface groups. Franz diffusion cells and confocal microscopy were employed to observe dendrimer interactions with full-thickness porcine skin samples. We have found that smaller PAMAM dendrimers (generation 2 (G2)) penetrate the skin layers more efficiently than the larger ones (G4). We have also found that G2 PAMAM dendrimers that are surface-modified by either acetylation or carboxylation exhibit increased skin permeation and likely diffuse through an extracellular pathway. In contrast, amine-terminated dendrimers show enhanced cell internalization and skin retention but reduced skin permeation. In addition, conjugation of oleic acid to G2 dendrimers increases their 1-octanol/PBS partition coefficient, resulting in increased skin absorption and retention. Here we report that size, surface charge, and hydrophobicity directly dictate the permeation route and efficiency of dendrimer translocation across the skin layers, providing a design guideline for engineering PAMAM dendrimers as a potential transdermal delivery vector.
ISSN:1525-7797
1526-4602
DOI:10.1021/bm300545b