Molybdenum-Iodine Cluster Loaded Polymeric Nanoparticles Allowing a Coupled Therapeutic Action with Low Side Toxicity for Treatment of Ovarian Cancer.

The ability of cancer cells to develop resistance to anti-cancer drugs, known as multidrug resistance, remains a major cause of tumor recurrence and cancer metastasis. This work explores the double mechanism of toxicity of (D, L-lactide-co-glycolide) acid (PLGA) nanoparticles encapsulating a molybdenum cluster compound, namely Cs[{MoI}(OOCCF)] (CMIF). Hemocompatibility and biocompatibility assays show the safe potential of CMIF loaded nanoparticles (CNPs) as delivery systems intended for tumor targeting for PDT of ovarian cancer with a slight hemolytic activity and a lack of toxicity up to 50 µM CMIF concentration.

From molecules to nanovectors: Current state of the art and applications of photosensitizers in photodynamic therapy.

Photodynamic therapy (PDT) is a concept based on a selective activation by light of drugs called photosensitizers (PS) leading to reactive oxygen species production responsible for cell destruction. Mechanisms of photodynamic reaction and cell photo-destruction following direct or indirect mechanisms will be presented as well as PS classification, from first generation molecules developed in the 1960 s to third generation vectorized PS with improved affinity for tumor cells. Many clinical applications in dermatology, ophthalmology, urology, gastroenterology, gynecology, neurosurgery and pneumology reported encouraging results in human tumor management.

Molybdenum cluster loaded PLGA nanoparticles as efficient tools against epithelial ovarian cancer.

In this study, poly (lactic-co-glycolic) acid nanoparticles loading inorganic molybdenum octahedral cluster were used for photodynamic therapy (PDT) of ovarian cancer. Three cluster compounds, ((CH)N)[{MoBr}Br], Cs[{MoBr}Br] and Cs[{MoI}(OOCF)] denoted TMB, CMB and CMIF were studied following their incorporation in nanoparticles by a nanoprecipitation method. All resulting nanoparticles exhibited physico-chemical characteristics such as size and zeta potential compatible with cellular uptake.

PLGA nanoparticles embedding molybdenum cluster salts: Influence of chemical composition on physico-chemical properties, encapsulation efficiencies, colloidal stabilities and in vitro release.

We present a screening of poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles embedding a series of inorganic molybdenum octahedral clusters intended for photodynamic therapy (PDT) of cancer. Three cluster compounds from 2 cluster units, [{MoBr}Br] and [{MoI}(OOCF)] were studied. [{MoBr}Br]cluster units are found in the soluble ternary salt Cs[{MoBr}Br] (CMB) prepared by solid state chemistry at high temperature.

Molybdenum cluster loaded PLGA nanoparticles: An innovative theranostic approach for the treatment of ovarian cancer.

We evaluate poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles embedding inorganic molybdenum octahedral cluster for photodynamic therapy of cancer (PDT). Tetrabutyl ammonium salt of MoBr cluster unit, (TBA)MoBr, presents promising photosensitization activity in the destruction of targeted cancer cells. Stable cluster loaded nanoparticles (CNPs) were prepared by solvent displacement method showing spherical shapes, zeta potential values around -30 mV, polydispersity index lower than 0.

Decline of multidrug-resistant Gram negative infections with the routine use of a multiple decontamination regimen in ICU.

Objectives: We have shown that the routine use of a multiple decontamination regimen with oropharyngeal and digestive polymyxin/tobramycin/amphotericin B plus mupirocin/chlorhexidine in intubated patients reduced all-cause acquired infections (AIs) in the intensive care unit (ICU). We now assessed the long-term impact of this strategy on AIs involving multidrug-resistant aerobic Gram negative bacilli (AGNB) and acquired episodes of extended-spectrum betalactamase (ESBL)-producing Enterobacteriaceae rectal carriage.

Methods: This was an observational single center study of all patients admitted to an ICU over 5 years (study population).

Population Pharmacokinetics of Amitriptyline After Intrathecal, Epidural, and Intravenous Administration in Sheep.

Background: Amitriptyline (AMI) is a lipophilic, tricyclic antidepressant with analgesic properties that could potentially be used for epidural (EPI) analgesia. However, no pharmacokinetic data are available for AMI in spinal spaces. The objective of this study was to evaluate the spinal disposition and intrathecal (IT) bioavailability of AMI after IT and EPI administration.

Formulation and stability study of a pediatric 2% phenylephrine hydrochloride eye drop solution.

Introduction: We present formulation and stability evaluation of a 2% (w/v) phenylephrine hydrochloride biocompatible eye drop solution, routinely prepared in hospital pharmacy under aseptic conditions, for retinal examination of neonates and premature infants.

Materials And Methods: Eye drop solution was formulated by dissolution of phenylephrine hydrochloride and disodium hydrogen phosphate as buffering agent in sterile water for injection and sodium chloride for injection as isotonic agent. The previous solution was sterile filtered through under aseptic conditions, in an iso class 5 air quality clean room under horizontal laminar airflow hood.

Preparation and characterization of spironolactone-loaded nano-emulsions for extemporaneous applications.

In neonates as well as in adults having swallowing difficulty, oral medication is given through a nasogastric tube making liquid formulations preferable. In this study, we present the high potential of nanometric emulsions formulated by spontaneous surfactant diffusion, as extemporaneous formulations of hydrophobic drug. Spironolactone used as hydrophobic drug model, was incorporated in oil before formulation at a concentration of 13.

Ex vivo and in vivo diffusion of ropivacaine through spinal meninges: influence of absorption enhancers.

Following epidural administration, cerebrospinal fluid bioavailability of local anesthetics is low, one major limiting factor being diffusion across the arachnoid mater barrier. The aim of this study was to evaluate the influence of absorption enhancers on the meningeal permeability of epidurally administered ropivacaine. Five enhancers known for their ability to increase drug permeability via transcellular and/or paracellular pathways, i.

Epidural, intrathecal and plasma pharmacokinetic study of epidural ropivacaine in PLGA-microspheres in sheep model.

Background: Microparticulate local anesthetics-loaded delivery systems are known to provide a controlled release of drug and to reduce systemic toxicity resulting from transient high plasma concentrations. The aim of this study was to evaluate epidural, intrathecal and plasma pharmacokinetics of ropivacaine following epidural administrations of repeated boluses or infusions and to compare them with the epidural administration of polylactide-co-glycolide ropivacaine-loaded microspheres.

Methods: In the first step, the epidural and intrathecal pharmacokinetics was evaluated in 3 Lacaunes ewes, receiving epidural continuous infusion of ropivacaine with increasing doses (20, 50 and 100mg/h).

Effect of epinephrine on epidural, intrathecal, and plasma pharmacokinetics of ropivacaine and bupivacaine in sheep.

Background: Local vasoconstriction induced by epinephrine added to epidural local anaesthetics has been shown to improve their quality and duration of action in several clinical reports. There are several assumptions on the mechanisms. This study was designed to evaluate the influence of epinephrine on transmeningeal uptake of epidurally administered ropivacaine and bupivacaine by measuring local anaesthetic concentrations in the epidural and intrathecal spaces and in plasma.

Alkalinization of intracuff lidocaine: efficacy and safety.

When alkalinized lidocaine instead of air is used to fill the endotracheal tube (ETT) cuff, coughing, and bucking are decreased during extubation when ventilation is controlled with N2O. However, sodium bicarbonate (NaHCO3) used to transform lidocaine hydrochloride (L-HCl) to lidocaine base induces a pH increase that could be irritating for mucosa in the case of cuff rupture. Therefore, we determined, in a randomized controlled study with controlled patient ventilation without N2O, whether the smallest concentrations of NaHCO3 (1.

Spinal disposition and meningeal permeability of local anesthetics.

Purpose: To investigate the spinal disposition, the cerebrospinal fluid (CSF) bioavailability, and the ex vivo meningeal permeability of six homologous pipecoloxylidide local anesthetics and to search for correlations with lipophilicity.

Methods: The ex vivo meningeal permeability was studied on fresh specimen of meninges (dura mater and arachnoid mater) removed from lumbar and cervical level of rabbit spine following laminectomy. Spinal disposition and CSF bioavailability were investigated using microdialysis sampling after simultaneous injection of an equimolar dose of the six homologs in the epidural or in the intrathecal spaces.

Bupivacaine containing dry emulsion can prolong epidural anesthetic effects in rabbits.

To assess the prolongation of epidural bupivacaine by a novel lipid formulation, a physically stabilized bupivacaine containing dry emulsion was prepared by spray-drying. Bupivacaine release from the oil-in-water emulsion was studied using an in vitro two-phase stirred model, then the pharmacodynamic effects and the pharmacokinetics of bupivacaine from the spray-dried emulsion were evaluated and compared to a bupivacaine hydrochloride solution, following a two-period cross-over epidural administration in rabbits. The in vitro release characteristics suggested an extended release of bupivacaine from the emulsion compared to the solution.

Prolongation of epidural bupivacaine effects with hyaluronic acid in rabbits.

To assess the prolongation of epidural bupivacaine by hyaluronic acid viscous formulations we designed a cross-over study in rabbits. Different doses of bupivacaine (3 or 6 mg) either as a solution (bupivacaine hydrochloride), or as viscous formulations with hyaluronic acid (bupivacaine base and bupivacaine hydrochloride) were administered in a rabbit model of epidural anesthesia. In the first part of the study, in vitro release characteristics were determined.

Alkalinization of intra-cuff lidocaine and use of gel lubrication protect against tracheal tube-induced emergence phenomena.

Background: We sought to determine the benefits of using alkalinized lidocaine 40 mg to fill the cuff of a tracheal tube (ETT) in combination with water-soluble gel lubrication to prevent post-intubation sore throat.

Methods: The work included an in vitro study of the diffusion of alkalinized lidocaine solution through the low-pressure, high-volume cuff of an ETT. We also performed a randomized controlled study (n=20 patients in each group) that included a group who received an alkalinized lidocaine-filled ETT cuff with lubrication of the tube using water-soluble gel (Group G), and two control groups who received an alkalinized lidocaine-filled cuff with ETT lubrication with water (Group W) or an air-filled cuff with ETT lubrication with water (Group C).

Spray-dried redispersible oil-in-water emulsion to improve oral bioavailability of poorly soluble drugs.

A physically stabilized dry emulsion dosage form reforming the original emulsion after rehydration was developed by spray-drying a liquid oil-in-water emulsion containing maltodextrin as carrier and sodium caseinate as emulsifying agent. Several oil:water as well as maltodextrin:water ratios were tested, the homogenization and spray-drying processes and the reconstitution properties were investigated and an optimum formulation was selected for poorly soluble drug incorporation, having an identical oil:water and carrier:water ratio of 10% (w/w) and a load of solid material of 20% (w/w). Lipophilic 5-phenyl-1,2-dithiole-3-thione (5-PDTT) was selected as a model drug.

Alkalinization of intracuff lidocaine improves endotracheal tube-induced emergence phenomena.

Unlabelled: We sought to evaluate the effect of filling an endotracheal tube cuff with 40 mg lidocaine alone (Group L) or alkalinized lidocaine (Group LB) in comparison to an Air Control group (Group C) on adverse emergence phenomena in a randomized controlled study (n = 25 in each group). The incidence of sore throat was decreased for Group LB in comparison to Group L during the 24 postextubation hours. The difference between Group L and Group C remained significant in the two postextubation hours only.

Endotracheal tube cuffs filled with lidocaine as a drug delivery system: in vitro and in vivo investigations.

The purpose of this study was to examine if lidocaine diffusion across an endotracheal tube cuff could improve post-operative tolerance, especially sore throat. The in vitro release of lidocaine from tube cuffs filled with different lidocaine formulations (base form, hydrochloride form or alkalinized lidocaine hydrochloride) was investigated. A preliminary pilot clinical study in anaesthesia for spine surgery in smoker patients was carried out to examine the pharmacokinetic (i.

[Biopharmaceutics of local anesthetic-cyclodextrin complexes following loco-regional administration].

In the research of new dosage forms improving the therapeutic index of local anesthetics, we studied cyclodextrins, cyclic oligosaccharides forming soluble inclusion complexes with various lipophilic drugs. Complexes between bupivacaine and hydroxypropyl-B-cyclodextrin, bupivacaine and sulfobutyl ether-7-B-cyclodextrin were studied in vivo, using an epidural and a perineural (sciatic) model, respectively. Biopharmaceutics and pharmacodynamics of bupivacaine were evaluated in the rabbit.

Spinal biopharmaceutics of bupivacaine and lidocaine by microdialysis after their simultaneous administration in rabbits.

The aim of the present study was to determine the intrathecal bioavailability of a mixture of lidocaine and bupivacaine in a rabbit model of spinal anesthesia by using the microdialysis technique. Catheter and microdialysis probe were inserted under control of the view either in the epidural or in the intrathecal space. First, the epidural disposition of the mixture of bupivacaine and lidocaine was studied after epidural administration.

Biopharmaceutics and pharmacokinetics of 5-phenyl-1, 2-dithiole-3-thione complexed with sulfobutyl ether-7-beta-cyclodextrin in rabbits.

The biopharmaceutics and pharmacokinetics of 5-phenyl-1, 2-dithiole-3-thione (5PDTT) were investigated in rabbits, after administration as a complex with sulfobutyl-ether-7-beta-cyclodextrin (SBE7-beta-CD) by intravenous and oral routes and as a micronized powder by oral route. 5PDTT had a rapid and large red blood cell partitioning that was not dependent on drug concentration either in vitro or ex vivo. The blood clearance was very high (354 +/- 131 mL/min) suggesting extrahepatic metabolism and/or nonrenal elimination and a significant volume of distribution (67 +/- 76 L).