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To assess Na-K-ATPase inhibiton and prostaglandin synthesis stimulation as the mechanism of the secretory (cathartic) action of phenolphthalein in the primate, we investigated water and electrolyte transport and Na-K-ATPase levels in monkey intestine. Both jejunum and colon were studied with in vivo perfusion and in vitro Ussing chamber techniques. Water, Na, and Cl absorption was inhibited or secretion was induced by phenolphthalein (10(-3) M) in the jejunum and colon when the drug was present in the mucosal bathing (perfusion) solution. Serosal addition of phenolphthalein (10(-4) or 10(-3) M) induced Na and anion absorption in the jejunum but not in the colon. Phenolphthalein inhibited Na-K-ATPase activity in the test tube, but assays of intestine previously perfused or bathed in the drug showed no inhibiton. Indomethacin, in doses sufficient to inhibit prostaglandin synthesis in the intestine, inhibited the secretion induced by phenolphthalein in the jejunum but not in the colon. These inconsistencies cast doubt on the role of Na-K-ATPase inhibition or the role of prostaglandin synthesis stimulation in the mechanism of action of phenolphthalein.

Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-poly(lactide) (mPEG-PLA) and polyoxyethylene-660-12-hydroxy stearate (Solutol HS15), were fabricated and used as a nanocarrier for solubilizing poorly soluble anesthetic drug propofol. The solubilization of propofol by the mixed micelles was more efficient than those made of mPEG-PLA alone. Micelles with the optimized composition of mPEG-PLA/Solutol HS15/propofol = 10/1/5 by weight had particle size of about 101 nm with narrow distribution (polydispersity index of about 0.12). Stability analysis of the mixed micelles in bovine serum albumin (BSA) solution indicated that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of the copolymer were efficiently screened by mPEG, and propofol-loaded mixed micelles were stable upon storage for at least 6 months. The content of free propofol in the aqueous phase for mixed micelles was lower by 74% than that for the commercial lipid emulsion. No significant differences in times to unconsciousness and recovery of righting reflex were observed between mixed micelles and commercial lipid formulation. The pharmacological effect may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs.

The purpose of this work was to explore the feasibility of ethosomes for improving the antiarthritic efficacy of tetrandrine by topical application. It was found that tetrandrine was a weak base (pK a = 7.06) with pH-dependent partition coefficient. The spherical-shaped ethosomes were prepared by pH gradient loading method. Ex vivo permeation and deposition behavior demonstrated that the drug flux across rat skin and deposition of the drug in rat skin for ethosomes was 2.1- and 1.7-fold higher than that of liposomes, respectively. Confocal laser scanning microscopy confirmed that ethosomes could enhance the topical delivery of the drug in terms of depth and quantity compared with liposomes. The ethosomes were shown to generate substantial enhancement of therapeutic efficacy of tetrandrine on Freund's complete adjuvant-induced arthritis with regard to liposomes. These results indicated that ethosomes would be a promising carrier for topical delivery of tetrandrine into and across the skin.

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The main objective of the present work was to prepare and assess dermal delivery of tacrolimus-loaded ethosomes versus classic liposomes. Both delivery systems were characterized for particle size, polydispersity index, and entrapment efficiency (EE), by dynamic laser diffraction and ultrafiltration or dialysis methods, respectively. The results indicated that presence of ethanol in the formulations affected the particle size. In addition, ultrafiltration method was selected to determine EE due to relatively short period as compared with dialysis method. Ethosomes exhibited a significant higher EE and amount of drug in dermis in contrast to classic liposomes suggesting that ethosomes with higher entrapment capacity prompted more amount of tacrolimus to permeate through stratum corneum and reach the target of atopic dermatitis (AD). Physical stability was very well for tacrolimus-loaded ethosomes under storage condition (4°C). Our results demonstrated that the ethosomal system might be a promising candidate for dermal delivery of tacrolimus for AD.

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