Novel Meta-iodobenzylguanidine and Etoposide Complex: Physicochemical Characterization and Mathematical Modeling of Anticancer Activity.

It is hypothesized that meta-iodobenzylguanidine (MIBG) complexation with etoposide (VP-16) will improve drug solubility and specificity towards BE(2)C neuroblastoma (NB) cells, 90% of which are known to be MIBG avid. After MIBG and VP-16 interaction, the dry complex was analyzed for crystalline structure, surface morphology, solubility, and size distribution by X-ray powder diffraction (P-XRD), scanning electron microscopy (SEM), infrared (FTIR) and UV spectroscopy, and dynamic light scattering. After exposure to the complex, the cell viability and decay rates were assessed by the MTS assay and estimated using exponential decay models (EDM).

Physico-chemistry and Cytotoxicity of Tenofovir-Loaded Acid Phosphatase-Responsive Chitosan Nanoparticles.

This study assesses the in vitro release of tenofovir (TFV)-loaded triphosphate (TPP) cross-linked chitosan nanoparticles (NPs) catalyzed by human prostatic acid phosphatase (hPAP) for 24 h. The physico-chemical characterization of the NPs included particle mean diameter (PMD), zeta potential (ζ), percent drug encapsulation efficiency (% EE), Fourier transform infra-red (FTIR) spectroscopy, powder X-ray diffractometry analysis (PXRD), and drug release kinetics. The first-order rate constant (k) and activation energy (E) of the cross-link (TPP) are determined by the integrated rate law and Arrhenius's equations.

Rheological analysis of a novel phenylboronic acid-closomer gel.

This study aims to characterize the rheological behavior of a novel phenylboronic acid (PBA)-based closomer nanoconjugate (Closogel) with potential application in pharmaceutical formulation. PBA was used as a cross-linking agent and model (antiviral) drug. The PBA loaded Closogel chemical structure was analyzed by boron (B) NMR and Fourier transform infrared (FTIR) spectroscopy.

Fluorine (F) Nuclear Magnetic Resonance Spectroscopy For Real Time Maraviroc Analysis From Microparticulate Systems.

Real time analysis of pharmaceuticals in controlled release nano and microsystems remains a challenge. It is hypothesized that fluorine 19 nuclear magnetic resonance (F qNMR) can be used for real time quantification and in vitro release of maraviroc (MVC). The release of maraviroc was analyzed in simulated body fluids from spray dried sodium alginate microspheres (MS) using the F qNMR method.

Direct and Real-Time Quantification Of Bortezomib Release From Alginate Microparticles Using Boron (B) Nuclear Magnetic Resonance Spectroscopy.

This study developed and validated a solution-state quantitative boron nuclear magnetic resonance (B qNMR) method for the real-time quantification of boron containing bioactive agents with emerging therapeutic applications. Hence, this study may offer an alternative analytic method to estimate drug potency, purity, stability, or in vitro release kinetics of boron-containing pharmaceutical formulations/compounds, especially in cases where dialysis is typically required but limited. The B qNMR method was linear in the range tested, and the detection and quantification limits were 1.

Preclinical Safety Evaluation of HIV-1 gp120 Responsive Microbicide Delivery System in C57BL/6 Female Mice.

Many novel vaginal/rectal microbicide formulations failed clinically due to safety concerns, indicating the need for the early investigation of lead microbicide formulations. In this study, the preclinical safety of an HIV-1 gp120 and mannose responsive microbicide delivery system (MRP) is evaluated in C57BL/6 mice. MRP was engineered through the layer-by-layer coating of calcium carbonate (CaCO) with Canavalia ensiformis lectin (Con A) and glycogen.

Engineering fast dissolving sodium acetate mediated crystalline solid dispersion of docetaxel.

It is hypothesized that a novel crystalline solid dispersion (CSD) of docetaxel (C-DXT) can be engineered by dispersing native docetaxel (DXT, a BCS class II drug) in sodium acetate crystal (SA). DXT is dissolved in glacial acetic/SA solution and freeze-dried. The resulting C-DXT is characterized by differential scanning calorimetry (DSC), powder X-ray analysis (PXRD), LC-MS/MS, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Quartz crystal microbalance with dissipation monitoring (QCM-D) and dynamic light scattering (DLS).

Layer-by-Layer Engineered Microbicide Drug Delivery System Targeting HIV-1 gp120: Physicochemical and Biological Properties.

The purpose of this study was to engineer a model anti-HIV microbicide (tenofovir) drug delivery system targeting HIV-1 envelope glycoprotein gp120 (HIV-1 g120) for the prevention of HIV sexual transmission. HIV-1 g120 and mannose responsive particles (MRP) were prepared through the layer-by-layer coating of calcium carbonate (CaCO) with concanavalin A (Con A) and glycogen. MRP average particle size ranged from 881.

Real-Time Analysis of Tenofovir Release Kinetics Using Quantitative Phosphorus (P) Nuclear Magnetic Resonance Spectroscopy.

The dialysis method is classically used for drug separation before analysis, but does not provide direct and real-time drug quantification and has limitations affecting the dialysis rate. In this study, a phosphorus nuclear magnetic resonance (P-qNMR) method is developed for the real-time quantification of therapeutic molecules in vitro. The release kinetics of model drug, tenofovir (anti-HIV microbicide), was analyzed in vaginal fluid simulant (VFS), seminal fluid simulant (SFS), and human plasma (HP) from chitosan nanofibers (size ∼100-200 nm) using the NMR (direct) method and compared with dialysis/UV-Vis (indirect) method.

Spray-Dried Thiolated Chitosan-Coated Sodium Alginate Multilayer Microparticles for Vaginal HIV Microbicide Delivery.

It is hypothesized that novel thiolated chitosan-coated multilayer microparticles (MPs) with enhanced drug loading are more mucoadhesive than uncoated MPs and safe in vivo for vaginal delivery of topical anti-HIV microbicide. Formulation optimization is achieved through a custom experimental design and the alginate (AG) MPs cores are prepared using the spray drying method. The optimal MPs are then coated with the thiolated chitosan (TCS) using a layer-by-layer method.

Tenofovir Containing Thiolated Chitosan Core/Shell Nanofibers: In Vitro and in Vivo Evaluations.

It is hypothesized that thiolated chitosan (TCS) core/shell nanofibers (NFs) can enhance the drug loading of tenofovir, a model low molecular weight and highly water-soluble drug molecule, and improve its mucoadhesivity and in vivo safety. To test this hypothesis, poly(ethylene oxide) (PEO) core with TCS and polylactic acid (PLA) shell NFs are fabricated by a coaxial electrospinning technique. The morphology, drug loading, drug release profiles, cytotoxicity and mucoadhesion of the NFs are analyzed using scanning and transmission electron microscopies, liquid chromatography, cytotoxicity assays on VK2/E6E7 and End1/E6E7 cell lines and Lactobacilli crispatus, fluorescence imaging and periodic acid colorimetric method, respectively.

Stimuli-sensitive thiolated hyaluronic acid based nanofibers: synthesis, preclinical safety and in vitro anti-HIV activity.

Aim: To develop a seminal enzyme bioresponsive, mucoadhesive nanofibers (NFs) as safe and effective nanocarriers for the prevention of HIV vaginal transmission.

Methods: A novel thiolated hyaluronic acid (HA-SH) polymer was synthesized to fabricate tenofovir (TFV)-loaded electrospun NFs (HA-SH-NFs) and characterized in vitro/in vivo.

Results: A triggered drug release (87% w/w) from the engineered HA-SH-NFs (mean diameter ∼75 nm) occured within 1 h under the influence of seminal hyaluronidase enzyme.

Label-Free Ferrocene-Loaded Nanocarrier Engineering for In Vivo Cochlear Drug Delivery and Imaging.

It is hypothesized that ferrocene (FC)-loaded nanocarriers (FC-NCs) are safe label-free contrast agents for cochlear biodistribution study by transmission electron microscopy (TEM). To test this hypothesis, after engineering, the poly(epsilon-caprolactone)/polyglycolide NCs are tested for stability with various types and ratios of sugar cryoprotectants during freeze-drying. Their physicochemical properties are characterized by UV-visible spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM/EDS).

Sodium Acetate Coated Tenofovir-Loaded Chitosan Nanoparticles for Improved Physico-Chemical Properties.

Purpose: It is hypothesized that sodium acetate (SA) can be used for in situ coating of drug loaded chitosan NPs for improved physico-chemical properties.

Methods: Tenofovir (TFV) is used as a model drug. Uncoated chitosan NPs are prepared by ionic gelation.

Application of Design of Experiment and Simulation Methods to Liquid Chromatography Analysis of Topical HIV Microbicides Stampidine and HI443.

This study intended to determine if experimental design and Monte Carlo simulation methods can be utilized to optimize the liquid chromatography (LC) analysis of active molecules. The method was applied for the simultaneous analysis of two topical microbicides, stampidine (STP) and HI443 in bulk and nanoformulations. The Plackett-Burman design was used for screening; whereas, Box-Behnken design was used to evaluate the main and interaction effects of the selected factors on the responses, namely peak area of STP (Y), HI443 (Y), tailing of STP (Y), and HI443 (Y).

Optimal Concentration of 2,2,2-Trichloroacetic Acid for Protein Precipitation Based on Response Surface Methodology.

For low protein concentrations containing biological samples (in proteomics) and for non proteinaceous compound assays (in bioanalysis), there is a critical need for a simple, fast, and cost-effective protein enrichment or precipitation method. However, 2,2,2-trichloroacetic acid (TCA) is traditionally used for protein precipitation at ineffective concentrations for very low protein containing samples. It is hypothesized that response surface methodology, can be used to systematically identify the optimal TCA concentration for protein precipitation in a wider concentration range.

Evaluation of degradation kinetics and physicochemical stability of tenofovir.

Tenofovir (TFV) has been proven to prevent the transmission of the Human Immunodeficiency Virus (HIV) through the vagina. But, there is little information available about its stability under various storage and stress conditions. Hence, this study aimed to investigate the degradation behavior and physicochemical stability of TFV using liquid chromatography coupled mass spectrometry (LC-MS) and solid state X-ray diffraction (XRD) analyses.

Resveratrol-loaded nanocarriers: formulation, optimization, characterization and in vitro toxicity on cochlear cells.

The present work aimed to investigate the suitability of polymeric nanoparticles (NPs) loaded with resveratrol (RES) for drug delivery to cochlear cells. RES-loaded NPs were prepared by a solvent-diffusion method without surfactant. The Box-Behnken design was used to study the effect of the formulation variables on the particle mean diameter (PMD), polydispersity index (PDI), zeta-potential (ζ), percent drug encapsulation efficiency (EE%), and ratio between NP size before and after freeze-drying (Sf/Si).

Concanavalin A-polysaccharides binding affinity analysis using a quartz crystal microbalance.

There is no comparative data available on the binding constants of Concanavalin A (Con A) and glycogen and Con A-mannan using quartz crystal microbalance (QCM), cost and time efficient system for biosensor analysis. It is hypothesized that a QCM can be used in its flow injection mode to monitor the binding affinity of polysaccharides to an immobilized lectin, Con A. The biosensor is prepared by immobilizing Con A on a 5MHz gold crystal by carbodiimide crosslinking chemistry.

Direct and real-time quantification of tenofovir release from ph-sensitive microparticles into simulated biological fluids using (1)h nuclear magnetic resonance.

In vitro drug release evaluation is a very important step toward the quality control of nano- or micro-particular drug delivery systems. However, most quantitative techniques such as high-performance liquid chromatography requires a dialysis membrane to separate the released free drug from these delivery systems, thus are not capable of direct detection and real-time quantification of the drug release kinetics. This study describes, for the first time, a rapid, specific, and direct method for the real-time quantification of in vitro tenofovir (TNF) release from pH-sensitive microparticles using a Varian 400 MHz (1)H nuclear magnetic resonance ((1)H-NMR) spectrometer.

Influence of surface chemistry on cytotoxicity and cellular uptake of nanocapsules in breast cancer and phagocytic cells.

The present work tests the hypothesis that stabilizers have a critical role on nanocarrier stealthiness and anticancer drug efficacy. Two different types of docetaxel (Doc)-loaded nanocapsules (NCs) stabilized with polysorbate 80 (NC(T80)) and polyvinyl alcohol (NC(PVA)) were synthesized using the emulsion solvent diffusion method. These NCs were characterized for particle mean diameter (PMD), drug content, morphology, surface composition, and degree of crystallinity.

Uptake and cytotoxicity of docetaxel-loaded hyaluronic acid-grafted oily core nanocapsules in MDA-MB 231 cancer cells.

Purpose: It is hypothesized that docetaxel (Doc)-loaded hyaluronic acid (HA)-polyethylene glycol/poly(ε-caprolactone)-grafted oily core nanocapsules (NCs) can enhance the drug cytotoxicity and uptake in CD44 expressing breast cancer (BC) cells (MDA-MB 231).

Methods: NCs were prepared, optimized and characterized by dynamic light scattering, transmission electron microscopy (TEM), and powder X-ray diffraction (PXRD). In vitro cytotoxicity tests [MTS, level of reactive oxygen species (ROS) and level of reduced glutathione (GSH)] were performed in BC cells.

Comparative biophysical properties of tenofovir-loaded, thiolated and nonthiolated chitosan nanoparticles intended for HIV prevention.

Aim: This study is designed to test the hypothesis that tenofovir-loaded (an anti-HIV microbicide) chitosan-thioglycolic acid-conjugated (CS-TGA) nanoparticles (NPs) exhibit superior biophysical properties for mucoadhesion compared with those of native CS NPs.

Materials & Methods: The NPs are prepared by ionotropic gelation. The particle mean diameter, encapsulation efficiency and release profile are analyzed by dynamic light scattering and UV spectroscopy, respectively.