Poly(amidoamine) Dendrimers Increase Antifungal Activity of Clotrimazole

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  • Winnicka Katarzyna
    Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Bialystok
  • Sosnowska Katarzyna
    Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Bialystok
  • Wieczorek Piotr
    Department of Microbiological Diagnostics, Faculty of Pharmacy, Medical University of Bialystok
  • Sacha Pawel Tomasz
    Department of Microbiological Diagnostics, Faculty of Pharmacy, Medical University of Bialystok
  • Tryniszewska Elzbieta
    Department of Microbiological Diagnostics, Faculty of Pharmacy, Medical University of Bialystok

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Clotrimazole (CLO) is a local imidazolic antifungal agent. A major problem associated with the successful formulation of effective dosage forms containing CLO is its poor aqueous solubility, which presents a hindrance for the local availability of CLO and limits the effective antifungal therapy. In the present study, the effects of various concentrations of poly(amidoamine) (PAMAM) dendrimers generation 2 (G2) and generation 3 (G3) with amine (PAMAM-NH2) or hydroxyl surface groups (PAMAM-OH) on aqueous solubility and antifungal activity of CLO were studied. The obtained results showed that all tested PAMAM dendrimers improved the solubility of CLO and the more potent were PAMAM-NH2 dendrimers. The increase in solubility of CLO was highest at dendrimer concentration of 10 mg/ml. Microbiology studies indicated that only PAMAM-NH2 dendrimers significantly increased the antifungal activity of CLO (a 4—32-fold increase in the antifungal activity compared to pure CLO) and the most potent was dendrimer PAMAM-NH2 G2. These observations indicate that PAMAM dendrimers might be considered as potential carriers of CLO and provide further impetus to evaluate these polymers for use in basic drug delivery studies and to design semisolid dosage forms based on dendrimers with antimicrobial drugs, like CLO.

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