Abstract
Hydrotropic solubilization of hydrophobic drugs requires supramolar amounts of hydrotropes with potential toxicity issues. We investigated the use of epigallocatechin gallate (EGCG) and tannic acid at millimolar concentrations, as hydrotrope-like solubilizing agents. Paclitaxel, docetaxel, amphotherecin B, curcumin, or rapamycin were dried down with EGCG or tannic acid from ethanol and then redissolved in aqueous media. Following centrifugation and filtration, the drug solubility was measured using HPLC. The uptake of docetaxel into cells from EGCG-based solutions was measured using radiolabeled drugs. Both EGCG and tannic acid effectively increased the aqueous solubility of all drugs from low levels (μg/mL) to high levels (mg/mL) in a concentration-dependent fashion at millimolar concentrations. Solutions were generally stable at room temperature over 24 h. Compared with micellar formulations, EGCG-based solutions of docetaxel demonstrated markedly improved drug uptake or transport levels in all cell lines. The use of these additives may provide improved formulation of various hydrophobic drugs using oral, parenteral, localized, or device-associated delivery systems.
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