Poly(amidoamine) dendrimers as skin penetration enhancers: Influence of charge, generation, and concentration
✍ Scribed by Venkata Vamsi K. Venuganti; Omathanu P. Perumal
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 252 KB
- Volume
- 98
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
The study investigates the influence of surface charge, generation and concentration of poly(amidoamine) (PAMAM) dendrimers on skin permeation of a model hydrophilic drug, 5-fluorouracil (5FU). Permeation studies were performed using excised porcine skin in a Franz diffusion cell. Saturated concentration of 5FU in isopropyl myristate was applied on the skin after pretreatment with dendrimers and 14 C labeled 5FU was analyzed using a liquid scintillation counter. The influence of dendrimer surface charge (G4-NH 2 , G3.5-COOH, and G4-OH), generations (G2-G6-NH 2 ) and concentration (0.1-10 mM of G4-NH 2 ) on skin permeation of 5FU were studied. The enhancement in drug permeability coefficient (K p ) was in the following decreasing order G4-NH 2 > G4-OH > G3.5-COOH. Dendrimer increased the skin permeation by increasing the skin partitioning of 5FU. Transepidermal water loss, skin resistance measurements and ATR-FTIR studies revealed that cationic dendrimers act by interacting with the skin lipid bilayers. Increase in G4-NH 2 concentration did not proportionally increase the skin permeation of 5FU. The 5FU K p was inversely related to the molecular weight of the dendrimer. G2-NH 2 dendrimer reduced skin resistance to a greater extent than higher generation dendrimers. Overall, the study showed that lower generation cationic dendrimer is more effective in enhancing the skin permeation of hydrophilic drugs.