Abstract: Provided is a pharmaceutical composition for permeabilizing fetal membranes including an active ingredient having a log K in the range of 2 to 4, where K is the octanol/water partition coefficient. The active ingredient may be, for example, bupivacaine, sodium lauryl sulfate or oleic acid. Further provided is a system for transfetal membrane transport. The system includes a probe unit adapted for insertion into a female reproductive tract and releasing a substance onto fetal membranes that permeabilizes the membranes. The system is also configured to apply ultrasound radiation to the fetal membranes to further increase the membrane permeability.

Abstract: The invention provides a system and method for trans-fetal membranes transport. A source of ultrasound sonication is used to deliver ultrasound sonication to fetal membranes to enhance the permeability of the fetal membranes of a gestational sac. In one embodiment, a device is used to collect substances transported from the interior of the gestational sac to the exterior of the gestational sac, such as amniotic or coelomic fluid. In another embodiment a device is used to deliver one or more substances, such as a drug, to an external surface of the fetal membranes.

Abstract: The present invention provides methods for loading of agents and substances into per-formed liposomes, preferably a suspension of pre-formed liposomes as well as to methods for the controlled quantum (step-wise) release of agents and substances from liposomes. One of the principle features of the methods of the invention is to expose the liposomes to ultrasound irradiation having predefined parameters, resulting in an increase in permeability of the liposomes, thereby permitting, respectively, the loading and/or release of agents and substances into and/or from the liposomes.

Abstract: Transdermal analyte monitoring systems (TAMS) having increased longevity and improved analyte detection are described herein. Kits for use with the TAMS and methods of using the TAMS and kits are also described. In a preferred embodiment, the TAMS includes a protective, semi-permeable membrane covering the surface of the hydrogel. The protective, semi-permeable membrane contacts with the skin of a user and prevents contamination or fouling of the hydrogel. Optionally, the hydrogel comprises one or more humectants and/or an immobilized enzyme. In another preferred embodiment, the TAMS contains at least one channel or pocket for increasing the amount of oxygen provided to the hydrogel. In one embodiment, a method for improving analyte detection by the TAMS is provided. For example, after the skin porosity is increased by an appropriate pretreatment, a skin preparation wipe is applied to the treated skin area and then the TAMS is applied to the treated area.

Abstract: A system, method, and device for non-invasive body fluid sampling is provided. According to one embodiment of the present invention, the system includes a controller that controls the generation of ultrasound; an ultrasonic applicator that applies the ultrasound to an area of biological membrane; a receiver that contacts the area of biological membrane and receives body fluid through and out of the area of biological membrane; and a meter that interacts with the receiver and detects the presence of at least one analyte in the body fluid in the receiver. The receiver may include a membrane and a medium, such as a hydrogel, a fluid, or a liquid, that is contained in the membrane.

Abstract: The invention according to an exemplary embodiment relates to a method for transporting a substance across a biological membrane comprising the steps of applying a delipidation agent to a portion of the biological membrane, applying a hydration agent to the portion of the biological membrane, sonicating the portion of the biological membrane, and transporting the substance across the biological membrane. The step of applying the delipidation agent may be carried out prior to or simultaneously with the step of applying the hydration agent. The hydration agent may be applied before, during, or after the sonication step. The methods according to exemplary embodiments of the invention can provide improved transdermal transport in applications such as continuous analyte extraction and analysis and transdermal delivery of drugs and vaccines.

Abstract: The invention provides a convenient and non-invasive means to prepare cells, tissues, and organs for electrical transmission and reception. In an embodiment of the invention, a control method comprises the use of at least one skin electrode, as a reference electrode, and an electrical sensor to measure periodically or continuously the skin's electrical conductance at the site of preparation. The dynamic change in the conductance through the skin is measured while the ultrasound is applied. Signal processing is performed on the measurement and the level of skin impedance change is controlled by performing a mathematical analysis and using the results of such analysis to control the application of ultrasonic energy. A desired level of skin impedance can be set at a predetermined value or based on a chosen level of skin integrity, subject's sensation of discomfort, or duration of the ultrasound application.

Abstract: The invention provides a convenient and non-invasive means to prepare cells, tissues, and organs for electrical transmission and reception. In an embodiment of the invention, a control method comprises the use of at least one skin electrode, as a reference electrode, and an electrical sensor to measure periodically or continuously the skin's electrical conductance at the site of preparation. The dynamic change in the conductance through the skin is measured while the ultrasound is applied. Signal processing is performed on the measurement and the level of skin impedance change is controlled by performing a mathematical analysis and using the results of such analysis to control the application of ultrasonic energy. A desired level of skin impedance can be set at a predetermined value or based on a chosen level of skin integrity, subject's sensation of discomfort, or duration of the ultrasound application.

Abstract: According to the present invention, a method for enhancing transdermal transport is disclosed. The method includes the steps of increasing a permeability of an area of a membrane with a permeabilizing device. The membrane may be, inter alia, biologic skin or synthetic skin. The permeabilizing device may be an ultrasound-producing device. A substance is transported into and through the area of the membrane. The substance may be a drug, a vaccine, or a component of interstitial fluid.

Abstract: Transdermal transport of molecules during sonophoresis (delivery or extraction) can be further enhanced by application of an electric field, for example, electroporation or iontophoresis. In a preferred embodiment the ultrasound is low frequency ultrasound which induces cavitation of the lipid layers of the stratum corneum (SC). This method provides higher drug transdermal fluxes, allows rapid control of transdermal fluxes, and allows drug delivery or analyte extraction at lower ultrasound intensities than when ultrasound is applied in the absence of an electric field.

Abstract: According to the present invention, a method for enhancing transdermal transport is disclosed. The method includes the steps of increasing a permeability of an area of a membrane with a permeabilizing device. The membrane may be, inter alia, biologic skin or synthetic skin. The permeabilizing device may be an ultrasound-producing device. A substance is transported into and through the area of the membrane. The substance may be a drug, a vaccine, or a component of interstitial fluid.

Abstract: The present invention is directed to apparatus and methods for producing homogenous cavitation. An ultrasound souce comprising an ultrasound transmitting element having an axis and a cross-section along the axis is disclosed The ultrasound transmitting element also has a first axial end and a second axial end operable to produce ultrasonic waves. The cross-section has an area having a maximum value at the first axial end and a minimum value at the second axial end. A method for producing homogenous cavitation at an area of skin comprises creating a volume of fluid having a uniformly dispersed concentration of cavitation nuclei adjacent the area of skin. Ultrasound is then applied to the volume of fluid and causes cavitation at the cavitation nuclei.

Abstract: The invention provides a convenient and non-invasive means to prepare cells, tissues, and organs for electrical transmission and reception. In an embodiment of the invention, a control method comprises the use of at least one skin electrode, as a reference electrode, and an electrical sensor to measure periodically or continuously the skin's electrical conductance at the site of preparation. The dynamic change in the conductance through the skin is measured while the ultrasound is applied. Signal processing is performed on the measurement and the level of skin impedance change is controlled by performing a mathematical analysis and using the results of such analysis to control the application of ultrasonic energy. A desired level of skin impedance can be set at a predetermined value or based on a chosen level of skin integrity, subject's sensation of discomfort, or duration of the ultrasound application.

Abstract: The present invention is directed to apparatus and methods for producing homogenous cavitation. An ultrasound souce comprising an ultrasound transmitting element having an axis and a cross-section along the axis is disclosed The ultrasound transmitting element also has a first axial end and a second axial end operable to produce ultrasonic waves. The cross-section has an area having a maximum value at the first axial end and a minimum value at the second axial end. A method for producing homogenous cavitation at an area of skin comprises creating a volume of fluid having a uniformly dispersed concentration of cavitation nuclei adjacent the area of skin. Ultrasound is then applied to the volume of fluid and causes cavitation at the cavitation nuclei.

Abstract: A system, method, and device for non-invasive body fluid sampling is provided. According to one embodiment of the present invention, the system includes a controller that controls the generation of ultrasound; an ultrasonic applicator that applies the ultrasound to an area of biological membrane; a receiver that contacts the area of biological membrane and receives body fluid through and out of the area of biological membrane; and a meter that interacts with the receiver and detects the presence of at least one analyte in the body fluid in the receiver. The receiver may include a membrane and a medium, such as a hydrogel, a fluid, or a liquid, that is contained in the membrane.

Abstract: Methods and devices for application of ultrasound to a small area of skin for enhancing transdermal transport. An ultrasound beam having a first focal diameter is channelled into a beam having a second, smaller diameter without substantial loss of energy. Higher energy ultrasound can be used while causing less pain. Alternatively, ultrasound energy is applied through a vibrating element positioned just contacting, above or extending into the skin. Use of the element facilitates extraction of analyte and may enhance drug delivery. A two step noninvasive method involves application of ultrasound to increase skin permeability and removal of ultrasound followed by transdermal transport that can be further enhanced using a physical enhancer.

Abstract: Methods and devices for application of ultrasound to a small area of skin for enhancing transdermal transport. An ultrasound beam having a first focal diameter is channelled into a beam having a second, smaller diameter without substantial loss of energy. Higher energy ultrasound can be used while causing less pain. Alternatively, ultrasound energy is applied through a vibrating element positioned just contacting, above or extending into the skin. Use of the element facilitates extraction of analyte and may enhance drug delivery. A two step noninvasive method involves application of ultrasound to increase skin permeability and removal of ultrasound followed by transdermal transport that can be further enhanced using a physical enhancer.

Abstract: Transdermal transport of molecules during sonophoresis (delivery or extraction) can be further enhanced by application of an electric field, for example, electroporation or iontophoresis. In a preferred embodiment the ultrasound is low frequency ultrasound which induces cavitation of the lipid layers of the stratum corneum (SC). This method provides higher drug transdermal fluxes, allows rapid control of transdermal fluxes, and allows drug delivery or analyte extraction at lower ultrasound intensities than when ultrasound is applied in the absence of an electric field.

Abstract: Methods and devices for application of ultrasound to a small area of skin for enhancing transdermal transport. An ultrasound beam having a first focal diameter is channelled into a beam having a second, smaller diameter without substantial loss of energy. Higher energy ultrasound can be used while causing less pain. Alternatively, ultrasound energy is applied through a vibrating element positioned just contacting, above or extending into the skin. Use of the element facilitates extraction of analyte and may enhance drug delivery. A two step noninvasive method involves application of ultrasound to increase skin permeability and removal of ultrasound followed by transdermal transport that can be further enhanced using a physical enhancer.

Abstract: The invention discloses a composition having a mixture of a pharmaceutically, medically or veterinarily acceptable polymer, preferable a poly (lactic-co-glycolic acid) copolymer (PLGA) containing between about 10 and 100 wt. % lactic acid (LA) units, preferably between about 50 and 90 wt. % LA units, and &agr;-(tetrahydrofuranyl)-&ohgr;-hydroxypoly(oxy-1,2-ethandiyl) (glycofurol). Methods of forming solid implants in situ in an animal body, said implants optionally comprising a drug or other biologically active agent, as well as the use of the compositions of the invention in the treatment of animal bodies, are also disclosed.