A method for localizing delivery of an agent to a target site in a subject is provided. The method allows accumulation and/or release of the agent at the target site in the subject through the use of an energy source.

The invention pertains to a lipid-based microbubble stably binding a plurality of nucleic acids, and a method of delivering the microbubble and nucleic acids to a specific target site using ultrasound. The delivered nucleic acids create transgenic cells (i.e., for example, a transgenic tumor cell), wherein the transgenic cell expresses the proteins encoded by the delivered nucleic acids. This technology provides a significant improvement for microbubble-drug delivery platforms as known microbubble do not efficiently bind nucleic acids. The improvements described herein include but are not limited to identifying proper lipid proportionality ratios and/or cationic surfactant layers that provide an optimum mechanical index compatible with ultrasonics. Microbubble perfusion and/or nucleic acid delivery may be performed by a combination of imaging and ultrasound/microbubble targeted delivery to simultaneously perform low power two-dimensional imaging and high power microbubble destruction. Such systems are useful in therapeutics and/or diagnostics. For example, the data disclosed herein shows proof of principle in conjunction with the delivery of therapeutic siRNA molecules to slow tumor growth.

Low-viscosity nucleic acid compositions that can be administered by oral or multiple parenteral routes may allow for less frequent dosing than nucleic acid products currently on the market. In particular, low-viscosity defibrotide formulations for subcutaneous, intramuscular, intradermal, and intraperitoneal administration are more convenient to the patient and/or are administered outside of the hospital setting. Formulations of the invention may be used for the treatment of numerous conditions including for example, treatment of peripheral arteriopathies, treatment of acute renal insufficiency, treatment of acute myocardial ischemia, and treatment and prevention of sinusoidal obstruction syndrome or VOD.

Devices and methods are provided for administering a drug to a biological tissue in a patient, such as by intracellular and/or dermal delivery. The device includes a piezoelectric pulse generator; and an array of microneedle electrodes electrically coupled to the piezoelectric pulse generator, wherein the device, following insertion of the microneedle electrodes into the biological tissue, is configured to generate and deliver one or more electrical pulses through the microneedle electrodes effective to electroporate cells in the biological tissue and enable delivery of a drug into the electroporated cells.

The present invention provides a wirelessly driven contact lens including a strain sensor capable of detecting an increase in intraocular pressure in real time and a drug reservoir capable of lowering the intraocular pressure by releasing a drug based on the increase in intraocular pressure. In the present invention, there may be provided a personal therapy system that measures intraocular pressure in real time and properly releases a therapeutic drug according to the intraocular pressure that is measured through the strain sensor and the drug reservoir for releasing a drug based on an intraocular pressure state of a glaucoma patient.

The present disclosure relates to compositions and methods for the regeneration and/or restoration of hair cells utilizing a composition or an agent that decreases expression of a gene in a tissue of the inner ear and a second agent.

Transfer of genetic and other materials to cells is conducted in a hands-free, automated and continuous process that includes flowing the cells between electroporation electrodes to facilitate delivery of a payload into the cells, while acoustophoretically focusing the cells. Also described is a control method for the acoustophoretic focusing of cells that includes detecting locations of cells flowing through a channel, such as with an image analytics system, and modulating a drive signal to an acoustic transducer to change the locations of the cells flowing in the channel. Finally, an electroporation driver module is described that uses a digital to analog converter for generating an electroporation waveform and an amplifier for amplifying the electroporation waveform for application to electroporation electrodes.

Compositions and methods for treating various cardiovascular disorders include targeted delivery of glutamate for impairing a targeted portion of the autonomic nervous system (ANS). Targeted delivery may be via direct injection into the targeted portion of the ANS or via vascular injection of magnetically-targetable nanoparticles.

Systems, devices and methods for modulation of sirtuins by neurostimulation. In particular, sirtuins may be modulated by stimulation of the vagus nerve. Further described herein generally are methods, systems and devices, for specifically modulating sirtuins, including sub-sets (types or localized regions) of sirtuins by vagus nerve stimulation (VNS).

The present invention relates to compositions containing nanoparticies and uses of said composition for transferring therapeutically active substances into cells by means of specifically coated nanoparticles. The chemical design of the particles is such that a large amount thereof is absorbed into the cells. No direct bond between nanoparticle and the therapeutically active substance is required for the transfer into the cells. Thanks to said transfer, an increased efficacy of the substance and simultaneously reduced systemic toxicity is achieved, i.e. an increase in the efficacy while the side effects are reduced.