BACKGROUND Each year in the U.S., nearly 50,000 prostate cancer patients exhibit a rise in PSA levels, which can indicate disease recurrence. For patients (pts) with biochemically recurrent prostate cancer (PC), we evaluated the effects of white button mushroom (WBM) powder on serum PSA levels; also, the tolerability and biological activity of WBM was determined. METHODS Pts with continuously rising PSA levels were enrolled. Dose escalation was conducted in cohorts of 6; this continued provided that no more than one patient per cohort experienced dose limiting toxicity (DLT). The primary objective was to evaluate treatment feasibility and associated toxicity. The secondary objectives were to determine the effect of WBM on both serum PSA and androgen levels; and evaluate WBM’s impact on myeloid-derived suppressor cells (MDSCs) and cytokine levels. RESULTS Thirty-six pts were treated; no DLT’s were encountered. Overall PSA response rate was 11%. Two pts receiving 8 and 14 gm/day demonstrated a PSA complete response (CR): their PSA declined to undetectable levels that continue for 49 and 30 months. Two pts, receiving 8 and 12 gm/day, experienced a PSA partial response (PR). After 3 months of therapy, 36% of pts (13/36) experienced some PSA decrease below baseline. Pts with PSA CR and PR demonstrated higher levels of baseline interleukin-15 (IL-15) than nonresponders; for this group, we observed therapy-associated declines in myeloid-derived suppressor cells (MDSCs). CONCLUSIONS Therapy with WBM appears to both impact PSA levels and modulate the biology of biochemically recurrent PC by decreasing immunosuppressive factors.

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Tacrolimus is a macrolide lactone and potent immunosuppressant. It is highly lipophilic and has very limited aqueous solubility. Tacrolimus is highly susceptible to hydrolysis which results in very limited stability in aqueous solutions. Besides this, tacrolimus also undergoes dehydration and epimerization. Cyclodextrin (CD) complexation can increase the solubility and stability of hydrophobic drugs in aqueous solutions through the formation of drug/CD complexes. The aim of this study was to investigate degradation kinetics, mechanism and stability of tacrolimus in aqueous CD solutions, with the ultimate goal of developing an aqueous vehicle for ophthalmic delivery. For this, phase-solubility and kinetic studies in aqueous solutions containing different CDs at different pH values were performed. Mass spectrometry studies were also performed to elucidate the degradation mechanism of the drug in aqueous CD solution. The study showed that the drug has maximum stability between pH 4 and 6 and hydrolysis was the main cause of tacrolimus degradation in aqueous 2-hydroxypropyl-βCD (HPβCD) solutions. βCD and its derivatives were the better CD solubilizers for tacrolimus. The solubility and stability studies were further conducted with CD and surfactants, which is tyloxapol, tween 80 and poloxamer 407, where the combination provided better results compared to individual components.

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Econazole nitrate (ECN) is a weakly basic drug with very low aqueous solubility that hampers its permeation through biological membranes and results in low ECN bioavailability. Formation of drug/cyclodextrin (drug/CD) inclusion complexes is a formulation technology that can be applied to enhance drug solubility in aqueous media. The aim of this study was to determine the effect of CD complexation and pH adjustments on the ECN solubility. The ECN pHsolubility and ECN/CD phase-solubility profiles were determined. The solubility of ECN in aqueous acidic solutions containing α-cyclodextrin (αCD) was relatively high and much higher than in aqueous γ-cyclodextrin (γCD) solutions under same conditions. The complexation efficiency of the ECN/CD complex was relatively low for the unionized drug. Formation of ECN/CD inclusion complex was verified by proton nuclear magnetic resonance spectroscopy. Formation of ECN/CD complexes enhanced the drug stability during autoclaving. γCD complexes self-assembled to form nanoand microparticles whereas αCD complexes had negligible tendency to selfassemble. Formation of CD complex nano-and microparticles was investigated by dynamic light scattering and by drug permeation through semipermeable membranes of different molecular weight cut-off. The largest aggregate fraction was observed for the unionized ECN in aqueous pH 7.5 solution containing high CD concentration, that is 10% (w/v) CD. It was shown that in acidic solutions ECN/αCD can enhance the antifungal activity to filamentous fungi. This was associated with the increased ECN solubility and increase of readily available ECN molecules in aqueous αCD solutions.