Extrinsic Fluorescent Dyes as Tools for Protein CharacterizationHawe, Andrea; Sutter, Marc; Jiskoot, Wim
doi: 10.1007/s11095-007-9516-9pmid: 18172579
Noncovalent, extrinsic fluorescent dyes are applied in various fields of protein analysis, e.g. to characterize folding intermediates, measure surface hydrophobicity, and detect aggregation or fibrillation. The main underlying mechanisms, which explain the fluorescence properties of many extrinsic dyes, are solvent relaxation processes and (twisted) intramolecular charge transfer reactions, which are affected by the environment and by interactions of the dyes with proteins. In recent time, the use of extrinsic fluorescent dyes such as ANS, Bis-ANS, Nile Red, Thioflavin T and others has increased, because of their versatility, sensitivity and suitability for high-throughput screening. The intention of this review is to give an overview of available extrinsic dyes, explain their spectral properties, and show illustrative examples of their various applications in protein characterization.
Intravesical Treatments of Bladder Cancer: ReviewShen, Zancong; Shen, Tong; Wientjes, M.; O’Donnell, Michael; Au, Jessie
doi: 10.1007/s11095-008-9566-7pmid: 18369709
For bladder cancer, intravesical chemo/immunotherapy is widely used as adjuvant therapies after surgical transurethal resection, while systemic therapy is typically reserved for higher stage, muscle-invading, or metastatic diseases. The goal of intravesical therapy is to eradicate existing or residual tumors through direct cytoablation or immunostimulation. The unique properties of the urinary bladder render it a fertile ground for evaluating additional novel experimental approaches to regional therapy, including iontophoresis/electrophoresis, local hyperthermia, co-administration of permeation enhancers, bioadhesive carriers, magnetic-targeted particles and gene therapy. Furthermore, due to its unique anatomical properties, the drug concentration-time profiles in various layers of bladder tissues during and after intravesical therapy can be described by mathematical models comprised of drug disposition and transport kinetic parameters. The drug delivery data, in turn, can be combined with the effective drug exposure to infer treatment efficacy and thereby assists the selection of optimal regimens. To our knowledge, intravesical therapy of bladder cancer represents the first example where computational pharmacological approach was used to design, and successfully predicted the outcome of, a randomized phase III trial (using mitomycin C). This review summarizes the pharmacological principles and the current status of intravesical therapy, and the application of computation to optimize the drug delivery to target sites and the treatment efficacy.
Dissolution Enhancement by Bio-Inspired Mesocrystals: The Study of Racemic (R,S)-(±)-Sodium Ibuprofen DihydrateLee, Tu; Zhang, Chyong Wen
doi: 10.1007/s11095-008-9554-ypmid: 18302008
PurposeThe aim of this paper is to enhance the dissolution rate of racemic (R,S)-(±)-sodium ibuprofen dihydrate via a bio-inspired method of growing mesocrystals.Materials and MethodsMesocrystals of racemic (R,S)-(±)-sodium ibuprofen dihydrate were successfully prepared from a supersaturated aqueous solution of racemic (R,S)-(±)-sodium ibuprofen dihydrate having the initial degree of supersaturation, S0, of 1.326 and the initial saturated concentration, C*, of 0.986 mol/l at 25°C with sodium dodecyl sulfate (SDS) at a concentration of 0.10 g/l. Dynamic light scattering, scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and optical microscopy with cross polarizers were employed to understand the formation mechanism and to characterize the superstructures of the SDS generated mesocrystals.ResultsThe SDS generated mesocrystals were the assembly of the oriented attachment of racemic (R,S)-(±)-sodium ibuprofen dihydrate nano-sized platelets under the mediation of the side-to-side interaction between SDS and racemic (R,S)-(±)-sodium ibuprofen dihydrate. The SDS generated mesocrystals contained a mixture of the racemic compounds in α- and β-forms and the resolved racemic conglomerate in γ-form with no detectable amount of SDS. The dissolution rate of the SDS generated mesocrystals was more rapid than the one of its counterpart made by conventional crystallization pathway.ConclusionsThe crystallization of racemic (R,S)-(±)-sodium ibuprofen dihydrate in the presence of SDS yielded well-faceted, well-separated, but almost perfectly three-dimensionally aligned nano-sized platelets. This kind of bio-inspired mesocrystal superstructure has definitely opened a new doorway for crystal engineering and pre-formulation design in pharmaceutical industry. The future work is to study the mesocrystal formation of some other active pharmaceutical ingredients in organic solvent systems and to develop an efficient method for screening the additives.