Identification of a series of substituted 2-piperazinyl-5-pyrimidylhydroxamic acids as potent histone deacetylase inhibitors.

Pursuing our efforts in designing 5-pyrimidylhydroxamic acid anti-cancer agents, we have identified a new series of potent histone deacetylase (HDAC) inhibitors. These compounds exhibit enzymatic HDAC inhibiting properties with IC(50) values in the nanomolar range and inhibit tumor cell proliferation at similar levels. Good solubility, moderate bioavailability, and promising in vivo activity in xenograft model made this series of compounds interesting starting points to design new potent HDAC inhibitors.

Effect of the unstirred water layer on permeability enhancement by hydrophilic cyclodextrins.

Saturated solutions of three test compounds, carbamazepine, griseofulvin and hydrocortisone, were prepared in aqueous buffer (pH 7.4) containing 0, 1, 5 and 10% HPbetaCD. The permeability and flux of the drugs though a PAMPA membrane at different unstirred water layer (UWL) thicknesses was determined.

Self-assembling PEG-p(CL-co-TMC) copolymers for oral delivery of poorly water-soluble drugs: a case study with risperidone.

Diblock PEG-p(CL-co-TMC) [methoxypoly(ethylene glycol)-poly(caprolactone/trimethylene carbonate)] copolymers form micelles spontaneously and significantly increase the solubility of poorly water-soluble drugs. The aim of this work was to assess these diblock copolymers as oral drug delivery systems in both in vitro and in vivo experiments using risperidone as a model drug. The permeation of risperidone through Caco-2 cell monolayers showed that the apparent permeation coefficient (Papp) was slightly reduced when risperidone was formulated with the copolymer.

Incorporation of drugs in an amorphous state into electrospun nanofibers composed of a water-insoluble, nonbiodegradable polymer.

Electrostatic spinning was applied to the preparation of drug-laden nonbiodegradable nanofiber for potential use in topical drug administration and wound healing. The specific aim of these studies was to assess whether these systems might be of interest as delivery systems for poorly water-soluble drugs. Itraconazole and ketanserin were selected as model compounds while a segmented polyurethane (PU) was selected as the nonbiodegradable polymer.