Effective elimination of cancer stem cells by magnetic hyperthermia.

Cancer stem cells (CSCs) are a subpopulation of cancer cells that have stem cell-like properties and are thought to be responsible for tumor drug resistance and relapse. Therapies that can effectively eliminate CSCs will, therefore, likely inhibit tumor recurrence. The objective of our study was to determine the susceptibility of CSCs to magnetic hyperthermia, a treatment that utilizes superparamagnetic iron oxide nanoparticles placed in an alternating magnetic field to generate localized heat and achieve selective tumor cell kill.

Distribution of aerosols in murine obliterative bronchiolitis lungs by fluorescent imaging.

Unlabelled: ABSTRACT Background: Obliterative bronchiolitis (OB) is a major obstacle to the success of lung transplantation and is also a serious complication of hematopoietic stem cell transplant. It has few therapeutic options and respiratory delivery of potential therapeutic drugs is hindered by the narrowed and occluded airways.

Methods: OB was induced in mice using an established protocol and lung function was assessed by plethysmograph.

Distribution of aerosols in mouse lobes by fluorescent imaging.

Better methods are needed to quantify the distribution of drug among the airways of the lungs of small animals to facilitate the development of agents that can target specific airways. Mice were exposed to aerosols of aluminum phthalocyanine tetrasulfonic acid (AlPCS) that ranged in concentration and size (0.2-2.

Deposition of aerosol particles in a model vitreous chamber.

The purpose of this study was to assess quantitatively the aerosol deposition in a model eye chamber to identify the mechanism(s) of deposition and delivery efficiency for application in retinal disease treated with vitrectomy. Dry aerosol particles were produced with mixtures of fluorescein and a variable concentration of cesium chloride, which ranged in aerodynamic size from 0.6 to 1.

Physicochemical properties and antifungal activity of amphotericin B incorporated in cholesteryl carbonate esters.

The antifungal activity of amphotericin B (AmB) incorporated in three cholesteryl carbonate esters (CCEs), sodium cholesteryl carbonate, cholesteryl palmityl carbonate, and dicholesteryl carbonate, was examined to assess their potential for use in a dry powder aerosol. Formulations containing dissolved AmB were stable for 6 months. The particle size varied inversely with liquid crystalline content with observed mass median aerodynamic diameters ranging from 4 to 8 μ m.

In vitro and in vivo lung deposition of coated magnetic aerosol particles.

The magnetic induced deposition of polydispersed aerosols composed of agglomerated superparamagnetic particles was measured with an in vitro model system and in the mouse trachea and deep lung for the purpose of investigating the potential of site specific respiratory drug delivery. Oleic acid coated superparamagnetic particles were prepared and characterized by TEM, induced magnetic moment, and iron content. The particles were dispersed in cyclohexane, aerosolized with an ultrasonic atomizer and dried by sequential reflux and charcoal columns.

Magnetic activated release of umbelliferone from lipid matrices.

Lipid matrices containing dispersed superparamagnetic iron oxide (SPIO) particles were investigated as a magnetic field-responsive drug delivery system. Lipid matrices were prepared by combining myristyl alcohol, fatty acid coated SPIO particles, and umbelliferone (UMB). With placement of the matrices into the release medium, initial UMB release was fast but fell to zero indicating a burst effect.

Measurement of the distribution of aerosols among mouse lobes by fluorescent imaging.

Lung samples were prepared to investigate the perturbing effects of light absorption for quantifying the fluorescence signal of aluminum phthalocyanine tetrasulfonic acid (AlPCS). Standard solutions of known concentration and depth were imaged with different exposure times and analyzed. The intensity was found to be a linear function of concentration, depth, exposure time, and area.

Magnetic deposition of aerosols composed of aggregated superparamagnetic nanoparticles.

Purpose: The deposition of magnetic particles was examined for the possibility of further enhancing the selectivity of inhalation drug administration for the treatment of lung cancer.

Methods: Superparamagnetic magnetite nanoparticles were prepared and ultrasonically atomized, dried, and passed through glass tubes in the presence and absence of a wedge-shaped permanent magnet. The change in the outlet aerosol size distribution due to magnetic deposition under various well-defined aerodynamic conditions and a measured magnetic field was determined by an aerodynamic particle sizer.

Inhalation adjuvant therapy for lung cancer.

Background: Lung cancer is the leading cause of new cancer cases and also is the number one cause of cancer death in both male and females in the United States and the world. Lung cancer is histologically separated into either small-cell (SCLC) or nonsmall-cell lung cancer (NSCLC). NSCLC is much more common, and can occur in the periphery (adenocarcinomas) or central airways (squamous cell carcinomas).

Concentration dependent aggregation properties of chlorhexidine salts.

Purpose: Chlorhexidine (CHX), a chemical antiseptic, is known to bind to dentin and has been shown to be effective in treating bacterial infections caused by microbes. The solubility and aggregation properties of CHX salts were determined to guide the development of a sustained release formulation for long-term disinfection.

Methods: The amount of CHX in solution was determined as a function of counterion concentration (chloride, acetate (Ac) or gluconate (G)) by UV spectrophotometry at 255nm.

Solubility properties of chlorhexidine salts.

Chlorhexidine (CHX) is effective in treating oral bacterial infections. The solubility was shown to be highly dependent on the salt present in solution. Gluconate enhances the amount of CHX diacetate in solution possibly through mixed micelles formation, because the solubility product is such that the concentration of CHX will exceed the critical micelle concentration.

Collisional solute release from thermally activated lipid particles.

Solid lipid particles were evaluated for their potential as a thermo-activated drug delivery system. Submicron-sized diphenylhexatriene (DPH)/myristyl alcohol particles were produced by an atomization/drying process and the release rate of DPH into sodium dodecyl sulfate (SDS) micellar solutions was measured. The results showed that the presence of micelles and thermal activation was necessary and sufficient for the release of DPH.

High-frequency ultrasonic atomization for drug delivery to rodent animal models - optimal particle size for lung inhalation of difluoromethyl ornithine.

A high-(8-MHz) and a low-(1.7-MHz) frequency ultrasonic transducer were compared for delivering aerosols to mouse lung. The aerosol concentration (mass of dry particles/volume of air) rose nonlinearly with solution concentration of difluoromethyl ornithine for both transducers.

Performance of the vibrating membrane aerosol generation device: Aeroneb Micropump Nebulizer.

The output and particle size distribution of several series of aqueous solutions were measured to define quantitatively the practical limits of the solution properties acceptable for aerosol production by the aeroneb micropump nebulizer. Aerosol output measurements were made gravimetrically and the particle size distributions were obtained by laser diffractometry. Solution properties were obtained from the literature by interpolation of the best-fit curve of the property plotted as a function of composition.

Evaluation of the compaction of sulfathiazole polymorphs.

The aim of this study was to relate the tableting performance assessed by an instrumented tableting machine to the mechanical properties measured by nanoindentation. Three different polymorphic forms of sulfathiazole were prepared by recrystallization, and the density and X-ray powder diffraction patterns were measured and compared with theoretical density and simulated powder patterns, respectively. Tablets were prepared using a series of applied pressures, and the results were subjected to energy analysis, three dimensional (3D) modeling, and the traditional Heckel analysis.

Measurement of process-dependent material properties of pharmaceutical solids by nanoindentation.

The purpose of this work was to evaluate nanoindentation as a means to characterize the material properties of pharmaceutical solids. X-ray diffraction of potassium chloride and acetaminophen showed that samples prepared by cooling a melt to a crystalline sample as opposed to slow recrystallization had the same crystal structure. With analysis of the force-displacement curves, the KCl quenched samples had a hardness that was 10 times higher than the recrystallized KCl, while acetaminophen quenched samples were 25% harder than the recrystallized samples.

Reflux drying of aerosols.

The goal of our efforts has been to generate high aerosolized drug concentrations, so that the entire inhaled dose may be delivered to the animal in a relatively short time interval, typically one minute or less. In this report, we have examined the use of a reflux condenser coupled with an external heat source as a means to dry aerosol particles. The specific interest was to examine the parameters influencing the drying process and identify practical experimental conditions that would allow drying of aerosol particles.

Characterization of pharmaceutical solids by scanning probe microscopy.

The force-displacement profiles of four well-characterized materials that represent both soft/hard and plastic/brittle materials have been obtained using a novel nanoindentation technique. Flat surfaces of acetaminophen, potassium chloride, sucrose, and sodium stearate were prepared by melting or recrystallization, and the melting points were measured. Topographic and the corresponding first derivative images were obtained both before and after indentation.

Interaction of bile salts with gastrointestinal mucins.

The properties of three mucins were examined to identify the structural features responsible for their functional difterences. Bovine submaxillary mucin (BSM), porcine gastric mucin (PGM), and rat intestinal mucin (RIM) were each characterized, and high carbohydrate contents were found for RIM and PGM. The amino acid compositions were typical of mucin glycoproteins, with over half comprising small, neutral amino acids.

Excluded volume effect of rat intestinal mucin on taurocholate/phosphatidylcholine mixed micelles.

The interaction of bile salt/phospholipid mixed micelles with an intestinal mucin has been investigated to provide the foundation for the transport of ingested fat and poorly water-soluble drugs through the intestinal mucous layer. Egg phosphatidylcholine (PC) was equilibrated with sodium taurocholate (TC) to generate several series of solutions, which had different intermicellar concentrations of TC. Within each series, each solution had the same IMC and thereby micelle sizes, but varied with respect to micelle concentration.

Solubilization of drugs by physiological mixtures of bile salts.

Purpose: The solubilization of a number of steroids was determined in bile salt simple micelles and a bile salt/phospholipid micellar system to provide a better basis to predict the extent of drug solubilization in vivo.

Methods: Excess solid drug was dispersed in taurodeoxycholate or mixed micelle solutions prepared with fixed mole ratios of taurocholate, taurodeoxycholate, taurochenodeoxycholate, glycodeoxycholate, glycocholate, and glycochenodeoxycholate with egg phosphatidylcholine. Drug concentrations were determined from the absorbance following centrifugation.

Examination of the solubilization of drugs by bile salt micelles.

The purpose of this review is to provide a critical examination of the reported solubilization of drugs by bile salt micelles. The underlying premise is that with better information regarding the inherent biological complexity, efforts to predict the oral bioavailability of drug will be enhanced. The common means of comparing the reported values was chosen to be the solubilization ratio.