rifampin and dimethyldioctadecylammonium

It is well accepted in contemporary biology that an ∼30 Å thick lipid bilayer film around living cells is a matter of life and death as the film typically delimits the environments that serve as a crucial margin. The dynamic organization of lipid molecules both across the lipid bilayer and in the lateral dimension are known to be crucial for cellular transport and molecular recognition by important biological macromolecules. Here, we study dilute (20 mM) Dioctadecyldimethylammonium bromide (DODAB) vesicles at different temperatures in aqueous dispersion with well-defined phases namely liquid crystalline, gel and subgel. The spectroscopic studies on two fluorescent probes 8-anilino-1-naphthalene sulfonic acid ammonium salt (ANS) and Coumarin 500 (C500), former in the head group region of the lipid-water interface and later located deeper in the lipid bilayer follow dynamics (solvation and fluidity) of their local environments in the vesicles. Binding of an anti-tuberculosis drug rifampicin has also been studied employing Förster resonance energy transfer (FRET) technique. The molecular insight concerning the effect of dynamical organization of the lipid molecules on the local dynamics of aqueous environments in different phases leading to molecular recognition becomes evident in our study.

Topics: Anilino Naphthalenesulfonates; Antitubercular Agents; Aquatic Organisms; Coumarins; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; Lipid Bilayers; Phase Transition; Quaternary Ammonium Compounds; Rifampin; Solvents; Temperature

Surface properties and aggregation behavior of cationic-cationic and cationic-non-ionic mixed surfactant systems viz. Dodecylethyldimethylammonium bromide (DDAB) with a series of double chain cationic surfactants (DiDDAB, DMDTAB, and DODAB) and non-ionic surfactants (Brij 96, Tyloxapol and Tween 80) were analysed using surface tension and transmission electron microscopy (TEM). The effect of chain length of cationic surfactant and hydrophilic-lypophilic balance (HLB) prominently observed in critical aggregation (cac) value. The aqueous solubility of anti-tuberculosis drug: rifampicin (RIF) was comparatively studied by UV-vis spectroscopy in presence of formulated micelles and vesicles. RIF was significantly solubilised in aqueous medium using all the formulated aggregates. RIF is very unstable in basic medium (above pH-7) and in oxidizing media. Therefore, stability at pH-13 as well as in strong oxidising environment was monitored using UV-vis spectroscopy. To trace the locus of the drug encapsulation in the micelles/vesicles, fluorescence spectroscopy and TEM studies were carried out. Both the techniques stemmed in complimentary results and confirmed that, RIF is majorly populated at polar medium in cationic-cationic vesicles and favour to reside at hydrophobic medium of the nonionic-cationic micelles.

Topics: Antitubercular Agents; Cations; Drug Carriers; Drug Liberation; Hydrophobic and Hydrophilic Interactions; Micelles; Nanoparticles; Plant Oils; Polyethylene Glycols; Polysorbates; Quaternary Ammonium Compounds; Rifampin; Solubility; Surface Properties; Surface Tension; Surface-Active Agents; Thermodynamics; Water

Cationic bilayers based on the inexpensive synthetic lipid dioctadecyldimethylammonium bromide (DODAB) have been useful as carriers for drug delivery, immunoadjuvants for vaccines and active antimicrobial agents.. Rifampicin (RIF) or isoniazid (ISO) interacted with DODAB bilayer fragments (BF) or large vesicles (LV). Dispersions were evaluated by dynamic light-scattering for zeta-average diameter (Dz) and zeta-potential (ζ) analysis; dialysis for determination of drug entrapment efficiency; plating and CFU counting for determination of cell viability of Mycobacterium smegmatis or tuberculosis, minimal bactericidal concentration (MBC) and synergism index for DODAB/drug combinations.. DODAB alone killed micobacteria over a range of micromolar concentrations. RIF aggregates in water solution were solubilised by DODAB BF. RIF was incorporated in DODAB bilayers at high percentiles in contrast to the leaky behavior of ISO. Combination DODAB/RIF yielded MBCs of 2/2 and 4/0.007 μg/mL against Mycobacterium smegmatis or Mycobacterium tuberculosis, respectively. Synergism indexes equal to 0.5 or 1.0, indicated synergism against the former and independent action, against the latter species.. In vitro, DODAB acted effectively both as micobactericidal agent and carrier for rifampicin. The novel assemblies at reduced doses may become valuable against tuberculosis.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Drug Carriers; Drug Compounding; Drug Synergism; Lipid Bilayers; Microbial Sensitivity Tests; Microbial Viability; Molecular Structure; Mycobacterium smegmatis; Mycobacterium tuberculosis; Quaternary Ammonium Compounds; Rifampin; Technology, Pharmaceutical