Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature

Many ads for SSRI antidepressants claim that the drugs boost brain serotonin levels. Lacasse and Leo argue there is little scientific evidence to support this claim

Substained release of insulin from insoluble inhaled particles

Conventional slow-acting insulin preparations for subcutaneous injection, e.g., suspensions of the complex with protamine and/or zinc, were reformulated as dry powders for inhalation and the insoluble aerosol tested for providing sustained insulin plasma levels. Large porous particles made of lactose, albumin, and dipalmitoylphosphatidylcholine, and incorporating insulin, protamine, and/or zinc chloride were prepared using spray-drying. Integrity of insulin after spray-drying and insulin insolubilization in spraydried particles was verified in vitro. The pharmacokinetic profile of the formulation delivered by inhalation and subcutaneous injection was assessed in vivo in the rat. The formulation process of insulin as dry powders did not alter insulin integrity and did not impede, in most cases, insulin insolubilization by protamine and/or zinc. Large porous insulin particles presented 7 μm mass mean geometric particle diameters, 0.1 g/ cm3 bulk powder tap densities and theoretical aerodynamic diameters suitable for deep lung deposition (in the range of 2.2-2.5 μm). The dry powders exhibited 40% respirable fractions in the Andersen cascade impactor and 58-75% in the Aero-Breather. Insoluble inhaled insulin provided sustained insulin plasma levels for half a day, similar to injected insulin, and exhibited a bioavailability of 80.5% relative to subcutaneous injection of the same formulation

Preparation of novel particles for inhalation

Particles incorporating a surfactant and/or a hydrophilic or hydrophobic complex of a positively or negatively charged therapeutic agent and a charged molecule of opposite charge for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the particles are made of a biodegradable material and have a tap density less than 0.4 g/cmand a mass mean diameter between 5 mum and 30 mum, which together yield an aerodynamic diameter of the particles of between approximately one and three microns. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of poly(lactic acid) or poly(glycolic acid) or copolymers thereof. Alternatively, the particles may be formed solely of a therapeutic or diagnostic agent and a surfactant. Surfactants can be incorporated on the particle surface for example by coating the particle after particle formation, or by incorporating the surfactant in the material forming the particle prior to formation of the particle. Exemplary surfactants include phosphoglycerides such as dipalmitoyl phosphatidylcholine (DPPC). The particles can be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide a variety of therapeutic agents. Formation of complexes of positively or negatively charged therapeutic agents with molecules of opposite charge can allow control of the release rate of the agents into the blood stream following administration

Particles for Inhalation Having Sustained Release Properties

The invention generally relates to a method for pulmonary delivery of therapeutic, prophylactic and diagnostic agents to a patient wherein the agent is released in a sustained fashion, and to particles suitable for use in the method. In particular, the invention relates to a method for the pulmonary delivery of a therapeutic, prophylactic or diagnostic agent comprising administering to the respiratory tract of a patient in need of treatment, prophylaxis or diagnosis an effective amount of particles comprising a therapeutic, prophylactic or diagnostic agent or any combination thereof in association with a charged lipid, wherein the charged lipid has an overall net charge which is opposite to that of the agent upon association with the agent. Release of the agent from the administered particles occurs in a sustained fashion

Preparation of particles for inhalation

Particles incorporating a surfactant and/or a hydrophilic or hydrophobic complex of a positively or negatively charged therapeutic agent and a charged molecule of opposite charge for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the particles are made of a biodegradable material and have a tap density less than 0.4 g/cm3 and a mass mean diameter between 5 mu m and 30 mu m, which together yield an aerodynamic diameter of the particles of between approximately one and three microns. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of poly(lactic acid) or poly(glycolic acid) or copolymers thereof. Alternatively, the particles may be formed solely of a therapeutic or diagnostic agent and a surfactant. Surfactants can be incorporated on the particle surface for example by coating the particle after particle formation, or by incorporating the surfactant in the material forming the particle prior to formation of the particle. Exemplary surfactants include phosphoglycerides such as dipalmitoyl phosphatidylcholine (DPPC). The particles can be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide a variety of therapeutic agents. Formation of complexes of positively or negatively charged therapeutic agents with molecules of opposite charge can allow control of the release rate of the agents into the blood stream following administration

Particles for inhalation having sustained release properties

The invention generally relates to a method for pulmonary delivery of therapeutic, prophylactic and diagnostic agents to a patient wherein the agent is released in a sustained fashion, and to particles suitable for use in the method. In particular, the invention relates to a method for the pulmonary delivery of a therapeutic, prophylactic or diagnostic agent comprising administering to the respiratory tract of a patient in need of treatment, prophylaxis or diagnosis an effective amount of particles comprising a therapeutic, prophylactic or diagnostic agent or any combination thereof in association with a charged lipid, wherein the charged lipid has an overall net charge which is opposite to that of the agent upon association with the agent. Release of the agent from the administered particles occurs in a sustained fashion

Formulation and physical characterization of large porous particles for inhalation

Purpose. Relatively large (>5 mu m) and porous (mass density < 0.4 g/cm(3)) particles present advantages for the delivery of drugs to the lungs, e.g., excellent aerosolization properties. The aim of this study was, first, to formulate such particles with excipients that are either FDA-approved for inhalation or endogenous to the lungs; and second, to compare the aerodynamic size and performance of the particles with theoretical estimates based on bulk powder measurements. Methods. Dry powders were made of water-soluble excipients (e.g., lactose, albumin) combined with water-insoluble material (e.g., lung surfactant), using a standard single-step spray-drying process. Aerosolization properties were assessed with a Spinbaler(TM) device in vitro in both an Andersen cascade impactor and an Aerosizer(TM). Results. By properly choosing excipient concentration and varying the spray drying parameters, a high degree of control was achieved over the physical properties of the dry powders. Mean geometric diameters ranged between 3 and 15 mu m, and tap densities between 0.04 and 0.6 g/cm(3). Theoretical estimates of mass mean aerodynamic diameter (MMAD) were rationalized and calculated in terms of geometric particle diameters and bulk tap densities. Experimental values of MMAD obtained from the Aerosizer(TM) most closely approximated the theoretical estimates, as compared to those obtained from the Andersen cascade impactor. Particles possessing high porosity and large size, with theoretical estimates of MMAD between 1-3 mu m, exhibited emitted doses as high as 96% and respirable fractions ranging up to 49% or 92%, depending on measurement technique

Preparation of particles for inhalation

Particles incorporating a surfactant and/or a hydrophilic or hydrophobic complex of a positively or negatively charged therapeutic agent and a charged molecule of opposite charge for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the particles are made of a biodegradable material and have a tap density less than 0.4 g/cm and a mass mean diameter between 5 mu m and 30 mu m, which together yield an aerodynamic diameter of the particles of between approximately one and three microns. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of poly(lactic acid) or poly(glycolic acid) or copolymers thereof. Alternatively, the particles may be formed solely of a therapeutic or diagnostic agent and a surfactant. Surfactants can be incorporated on the particule surface for example by coating the particle after particle formation, or by incorporating the surfactant in the material forming the particle prior to formation of the particle. Exemplary surfactants include phosphoglycerides such as dipalmitoyl phosphatidylcholine (DPPC). The particles can be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide a variety of therapeutic agents. Formation of complexes of positively or negatively charged therapeutic agents with molecules of opposite charge can allow control of the release rate of the agents into the blood stream following administration

Preparation de particules pour inhalation

Cette invention se rapporte à des particules, dans lesquelles sont incorporés un tensioactif et/ou un complexe hydrophyle ou hydrophobe constitué par un agent thérapeutique chargé positivement ou négativement et par une molécule chargée de charge opposée pour l'administration de médicaments dans le système pulmonaire, ainsi qu'à des procédés pour la synthèse et l'administration de ces particules. Dans un mode de réalisation préféré, les particules sont constituées d'un matériau biodégradable et possèdent une densité après tassement inférieure à 0,4 g/cm et un diamètre médian massique compris entre 5 mu m et 30 mu m, qui produisent ensemble un diamètre aérodynamique des particules compris approximateivement entre 1 et 3 microns. Ces particules peuvent être formées de matériaux biodégradables, tels que des polymères biodégradables. Ces particules peuvent par exemple être formées d'acide polylacétique ou d'acide polyglycolique ou de copolymères de ceux-ci. Dans une variante, ces particules peuvent être formées uniquement d'un agent thérapeutique ou diagnostique et d'un tensioactif. Les tensioactifs peuvent être incorporés sur la surface des particules, par exemple par enrobage de la particule après sa formation, ou par incorporation du tensioactif dans le matériau formant la particule avant sa formation. Ces tensioactifs sont par exemple des phosphoglycérides, tels que la dipalmitoyl-phosphatidylcholine (DPPC). Ces particules peuvent être efficacement atomisées pour être administrées à l'appareil respiratoire, afin de permettre l'apport systémique ou local d'une grande variété d'agents thérapeutiques. La formation de complexes d'agents thérapeutiques chargés positivement ou négativement avec des molécules de charge opposée peut permettre de régler le taux de libération de ces agents dans le sang après leur administration