Abstract: Particles are provided which are suitable for delivery from a particle-mediated delivery device. The particles are obtained by precipitating a nucleic acid on inert metal carrier particles in the presence of a nucleic acid condensing agent and a metal ion chelating agent. Also described are processes for preparing the particles, and therapeutic methods using the particles including methods of nucleic acid immunization and gene therapy.

Abstract: A kit of parts for use in the manufacture of a particle cassette for a needleless syringe device. The kit may include a first cassette part having a first rupturable membrane sealed thereto and a second cassette part having a second rupturable membrane sealed thereto. The first and second cassette parts may be arranged to be attachable together so as to create a chamber for the confinement of particles between the first and second membranes. The first and second cassette parts may be substantially annular and the first cassette part defines a receptacle for receiving particles. The second cassette part may be attachable concentrically around or inside the first cassette part.

Abstract: A needleless syringe having a membrane (28) which is ruptured by gas pressure to generate a supersonic gas flow in which particles containing a therapeutic agent are injected.

Abstract: The invention provides a silencer and silencing method which ensures adequate silencing with no deleterious increase in back pressure (which creates a lift-off force) or decrease in device performance. Pressurized gas is supplied to a driver chamber by a bleed-hole having an effective bleed-hole area and, during use of the device for particle delivery, gas is vented to the atmosphere via a silencer having an effective venting area. The bleed-hole area and venting area are chosen to ensure that the mass flow rate of gas through the effective venting area is substantially equal to or greater than the mass flow rate of gas through the effective bleed-hole area. This ensures that there is no build up of gas in the silencer device which tends to increase back pressure and hence lift-off force. Preferred embodiments of the device comprise a silencer having a large volume and a small particle exit opening. Further, there is disclosed an embodiment using one or more transfer ducts to assist particle mixing.

Abstract: There is disclosed an apparatus and method which is capable of dispensing very small (typically less than 5 mg) quantities of particles to a high accuracy in a repeatable way and without undue wastage. Also, the need for advanced particle formulation is reduced. The apparatus comprises a closed loop control system which uses an electro-mechanical actuator to deliver impact energy to a supply of particles initially held on a sieve in a hopper. The impact energy causes a small number of particles to fall through the sieve and onto a weight measuring balance. The weight obtained is scrutinised by a processor to see if further actuations are required. In preferred embodiments, the energy of actuation is varied in accordance with the rate of dispensation calculated by the processor. Also, a correction amount can be obtained to take account of the fact that the balance can take a considerable amount of time to settle to its final value.

Abstract: A needleless syringe having a membrane (28) which is ruptured by gas pressure to generate a supersonic gas flow in which particles containing a therapeutic agent are injected.

Abstract: A method of distributing particles in a flow of gas and a needleless syringe for use in the needleless injection of particles into the skin or mucosa of a vertebrate subject are disclosed. The syringe includes a convergence which reduces pressure of the gas flowing in the gas flow path due to the Venturi effect such that particles initially located outside of the gas flow path are drawn into the gas flow path under the action of the reduced pressure and become entrained in the gas. An exit nozzle accelerates the particles so entrained. In another aspect of the invention, there is provided a method of creating a gas flow in a needleless syringe which comprises flowing gas through a first convergence into a chamber to form a transsonic gas jet in the chamber and passing the gas jet from the chamber into a second convergence and along the nozzle.

Abstract: There is disclosed an apparatus and method which is capable of dispensing very small (typically less than 5 mg) quantities of particles to a high accuracy in a repeatable way and without undue wastage. Also, the need for advanced particle formulation is reduced. The apparatus comprises a closed loop control system which uses an electromechanical actuator to deliver impact energy to a supply of particles initially held on a sieve in a hopper. The impact energy causes a small number of particles to fall through the sieve and onto a weight measuring balance. The weight obtained is scrutinised by a processor to see if further actuations are required. In preferred embodiments, the energy of actuation is varied in accordance with the rate of dispensation calculated by the processor. Also, a correction amount can be obtained to take account of the fact that the balance can take a considerable amount of time to settle to its final value.

Abstract: A process for producing a powder comprises spray freeze-drying an aqueous solution or suspension comprising a pharmaceutical agent, said solution or suspension having a solids content of 20% by weight or more. The spray freeze-dried powder may be administered to a subject via a needleless syringe.

Abstract: A needleless syringe particle delivery system is provided. The needleless syringe has an elongate nozzle that is connected at its upstream end to a sealed chamber. The sealed chamber contains gas at super-atmospheric pressure and particles of a therapeutic agent. Upon release of the gas from the sealed chamber, a flow is formed which entrains the particles and allows the particles to pass through the nozzle at supersonic speed for subsequent delivery to a target surface.

Abstract: A syringe, for use in the delivery of a dose of a therapeutic agent entrained within a pressurized fluid flow, includes an upstream portion, an intermediate portion, a downstream portion, and an actuator mechanism for initiating a flow of the fluid through the syringe. The upstream portion is interfaced with a source of fluid under pressure. The intermediate portion, which is interposed between the upstream and downstream portions, includes first and second members that are coupled together to provide a closed pocket for containing the dose. One of the first and second members is moveable relative to the other within the syringe to provide an open configuration in which the pocket is opened to expose the dose for entrainment by the fluid as it flows through the intermediate portion and to and through the nozzle. Also provided is a capsule formed from the first and second members.

Abstract: There is disclosed an apparatus and method which is capable of dispensing very small (typically less than 5 mg) quantities of particles to a high accuracy in a repeatable way and without undue wastage. Also, the need for advanced particle formulation is reduced. The apparatus comprises a closed loop control system which uses an electro-mechanical actuator to deliver impact energy to a supply of particles initially held on a sieve in a hopper. The impact energy causes a small number of particles to fall through the sieve and onto a weight measuring balance. The weight obtained is scrutinized by a processor to see if further actuations are required. In preferred embodiments, the energy of actuation is varied in accordance with the rate of dispensation calculated by the processor. Also, a correction amount can be obtained to take account of the fact that the balance can take a considerable amount of time to settle to its final value.

Abstract: A method is provided for in vivo or ex vivo delivery of a preparation of powdered nucleic acid molecules into vertebrate tissue for transformation of cells in the tissue using needleless injection techniques. The method can be used to deliver therapeutically relevant nucleotide sequences to cells in mammalian tissue to provide gene therapy, elicit immunity or to provide antisense or ribozyme functions. A method for providing densified processed pharmaceutical compositions is also described. The method is used to convert non-dense pharmaceutical powders or particulate formulations into densified particles optimally suited for transdermal delivery using a needleless syringe. The method is also used to optimize the density and particle size of powders and particulate formulations for subsequent transdermal delivery thereof. Densified pharmaceutical compositions formed by the present methods are also provided.

Abstract: A needleless syringe having a membrane (28) which is ruptured by gas pressure to generate a supersonic gas flow in which particles containing a therapeutic agent are injected.

Abstract: Replaceable components for use with a needleless syringe delivery device are provided. One replaceable component is a cartridge having a source of particles and a source of compressed gas. Another replaceable component is a nozzle assembly having a particle acceleration nozzle and a coaxial filter element. Reusable needleless syringe devices which include these replaceable components are also provided.

Abstract: Polynucleotides encoding at least one immunizing antigen whose expression is controlled by a promoter derived from a gene encoding a co-stimulatory molecule are provided. The polynucleotides may also encode adjuvants. Compositions comprising at least one immunizing agent and at least one cytokine that enhance dendritic cell stimulation and/or survival are also provided. Methods for eliciting an immune response against the immunizing agent are also provided. The method includes the steps of administering the polynucleotides and, optionally, co-administering an adjuvant.

Abstract: A needleless syringe capable of accelerating particles comprising a therapeutic agent across skin or mucosal tissue of a vertebrate subject is provided. The syringe comprises a body having a lumen with a diaphragm located adjacent to a terminus thereof. Particles comprising a therapeutic agent are delivered from an external surface of the diaphragm by means of the motive force provided by the impact of a gaseous shock upon the internal surface of the diaphragm. A method for transdermally delivering particles comprising a therapeutic agent from the needleless syringe is also provided.

Abstract: Spray-coated pharmaceutical powder compositions for transdermal administration using a needleless syringe comprise seed particles coated with a pharmaceutical composition, the said coated seed particles having an average size of about 10 to 100 &mgr;m and having an envelope density ranging from about 0.1 to about 25 g/cm3.

Abstract: A needleless syringe comprising a body containing a lumen, an upstream end of which is, or is arranged to be, connected to a source of gaseous pressure which can suddenly be released into the lumen; the downstream end of the lumen terminating behind a bistable diaphragm which is movable between an inverted position in which it presents outwardly of the body a concavity for containing particles of a therapeutic agent, and an everted, outwardly convex, position; the arrangement being such that, in use, when gas under pressure is released into the lumen, the diaphragm will snap over from its inverted to its everted position and catapult the particles outwardly.