Several crosslinking strategies exist to generate injectable materials. However, the vast majority of materials have very rapid gelation kinetics, which do not allow for complex injection routes via catheter where the material must remain at body temperature inside the catheter for a period of time. An example of such a delivery route is cardiac catheter delivery, where the material must remain liquid in the catheter to facilitate multiple injections to the damaged region of the heart. The delivery of injectable materials into the heart has been studied to encourage endogenous cell infiltration and repair as well as for the delivery of cells or other therapeutics. These studies have, however, largely been performed in small animals since the gelation kinetics of most injectable materials prevent cardiac catheter delivery. (more...)

A method of reducing, delaying, preventing, and/or inhibiting the progression of a Cryptococcus infection into the central nervous system and a method for delivery of therapeutic agents to the central nervous system. (more...)

Systemic chemotherapy has been associated with damage to healthy tissue and in some cases induction of secondary malignancies. Transarterial chemo-embolization (TACE) is a commonly used procedure in hepatic malignancies designed to reduce the systemic dose. TACE therapy involves administration of chemotherapy directly to the liver via a catheter which is inserted through the femoral artery to the hepatic artery that directly feeds the hepatic tumor. The blood supply to the tumor is then embolized following chemotherapy to further increase the dose to the tumor tissue. Nonetheless, even with TACE up to 50% of administered doxorubicin (Dox) passes directly through hepatic tumors into the systemic circulation. To further increase tumor dose while reducing systemic exposure, UCSF scientists have developed a novel catheter incorporating a chemotherapy filter that is positioned transiently during TACE so as to bind Dox that has passed through the tumor before it enters the systemic circulation. (more...)

Short interfering RNA (siRNA), possessing the unique capability to specifically knock down the undesired expression of genes, holds great promise as therapeutics for human diseases.  However, its clinical applications are constrained by the lack of a delivery vehicle that is safe, stable, and efficient.  To date, various delivery systems have been proposed, including cationic liposomes, cell-penetrating peptides (CPP), and cationic polymers.  Cationic liposomes and lipids are used widely for in-vitro studies with high effectiveness; however, their toxicity and low efficiency restrain in-vivo application.  For the CPP-based approach, siRNA-CPP complexed particles exhibit significantly improved delivery efficiency, but remain generally unstable, particularly, against serum nucleases.  For the cationic-polymer-based approach, siRNA is assembled with cationic polymers mainly through the electrostatic interactions, which improves intracellular delivery efficiency.  However, similar to the CPP-based approach, such assembled systems are unstable, which may readily dissociate and release their siRNA payload before reaching the cytoplasm of the target cells.  Therefore, in spite of such intensive efforts, the design and synthesis of an effective delivery vehicle for siRNA remains challenging. (more...)

There is an ever-increasing knowledge base concerning the molecular signatures of specific diseases and their potential in personalized medicine. Within this context, “theranostic” agents are of particular interest since they combine in vivo imaging for diagnostics and therapeutics within a single system. Current structural imaging techniques do not capitalize on the molecular basis of disease to add specificity. While structure imaging is oftentimes sufficient to answer general clinical questions, it has been inadequate in assessing molecular characteristics of diseased tissues (i.e., tumors). At times, structural imaging techniques are unable to discern benign from malignant tissue, such as lymph nodes or lung nodules. New methods and compositions are needed to fill the void and expand the reach of therapy by allowing the visualization, characterization, and measurement of biological processes at the molecular and cellular levels. (more...)

More than 1.5 billion people worldwide suffer from chronic pain.  Current therapies directed toward controlling pain, including potent narcotics and local nerve inactivation, are often inadequate treatments.  In addition, these therapies may lead to negative side effects, such as central nervous system depression, neurologic deficits, and risk of addiction.  The majority of pain is known to originate from the peripheral pain receptors and is due to their prolonged and persistent activation.  The ability to block or reduce the signaling from this point of origin has high potential for the development of novel pain management therapies.  (more...)

University of California researchers have developed a novel transparent zirconia cranial implant where laser light can more readily be delivered through the skull and thus maximizing laser light penetration to multiple affected areas within the brain.  The transparent zirconia implants, made of Yttria-Stablized Zirconia (YSZ), are placed underneath the scalp, either permanently or temporarily, and potentially instrumented with waveguides and optical fibers to deliver and/or acquire laser light to shallow or deep brain targets. Of all the synthetic materials that are commonly used for cranial implants (e.g. Ti, alumina, hydroxyapatite, and acrylic), only acrylic provides sufficient transparency. However, the intrinsic brittleness of this material predisposes it to catastrophic failure. YSZ implants represent an attractive alternative in this regard, due to its much higher toughness as well as its low thermal conductivity and proven biocompatibility in dental and orthopedic applications. By providing this “window” to the brain, in vivo optical diagnostics can monitor the imaging of the laser light-tissue interactions and post-operatory evolution of targeted brain tissue.    (more...)

A major goal for synthetic biology is to develop non-natural cellular systems. The substitution of efficient man-made reactions for key biochemical processes may offer a general route toward synthetic biological systems. One such biomimetic reaction is the generation of phospholipid membranes, useful not only in the study of synthetic biology, but having commercial applications for bulk synthesis in a variety to package a number of compounds including therapeutics, cosmetics, imaging agents, and genetic material. (more...)

The use of cell transplantation in the brain shows great promise for the treatment of human neurological diseases, such as Parkinson's disease or stroke. Indeed, pre-clinical studies in animal models have shown significantly improved neurological function following cell grafting. However, in human trials the results have been considerably more variable. This has, in part, been attributed to concerns with poor cell distribution within the target area. A further issue that has arisen with the challenge of scaling up from animal models to humans is the increase in the number of transcortical penetrations required to deliver therapeutic agents. For surgical cell transplantation approaches, cell sedimentation and impaired graft viability are also concerns that need to be addressed to optimize the use of this therapeutic avenue. (more...)

Liposomal carriers are hollow spherical structures that have been widely used to improve the delivery, extend the circulation time and decrease the toxicity of a number of drugs in development and approved for human use. However, many drug chemotypes are inefficiently loaded. One such chemotype includes drugs that cannot be readily dissolved in water. These 'hydrophobic' compounds require suspension in detergents for ultimate incorporation into the wall of the liposome, which greatly limits the loading capacity. In order to gain access to the vastly superior capacity of the hollow internal cavity of the liposome, UC researchers have developed a counter-intuitive and highly efficient method for encapsulating challenging drug chemotypes. (more...)

RNAi responses have great potential to treat human disease, especially cancer and viral infections.  However, siRNAs are macromolecules with no bioavailability to enter cells and require a delivery agent.  Here we developed RNAi-molecules delivered into cells by the TAT Peptide Transduction Domain (PTD) peptide.  Although we have only performed cell culture experiments, the technology holds promise for eventual development of RNAi therapeutics. (more...)

Fluorescence tomography (FT) is a sensitive but intrinsically low spatial resolution imaging modality due to strong photon scattering in biological tissue. Recently, a temperature-responsive fluorescence contrast agent has been reported using ICG loaded pluronic nanocapsules. The temperature dependence of these contrast agents provides a major opportunity to overcome the spatial resolution of regular FT by using temperature modulation/tagging.Researchers at the University of California, Irvine have developed a new molecular optical imaging modality termed “temperature-modulated fluorescence tomography (TM-FT)” that can provide high resolution images without sacrificing the exceptional sensitivity of fluorescence-based detection. TM-FT is based on the temperature modulation of fluorescence quantum efficiency in a highly scattering medium. The medium is irradiated by both excitation light and a high intensity focused ultrasound (HIFU) wave. The crucial benefit of HIFU is that the temperature of the medium is modulated with a very high spatial resolution (~1.5 mm) due to the absorption of acoustic power in the ultrasound focal zone. When the temperature sensitive fluorescence agent presents within HIFU focal zone, the local temperature increases and in turn, changes the fluorescence quantum efficiency inside the focal zone. As a result, the emitted fluorescence light intensity and lifetime have detectable change only when the agent is present within the focal zone. In other words, it allows fluorescence reconstruction with high spatial resolution by scanning focused ultrasound column over the medium while detecting the change in fluorescence signal. Using a proper reconstruction algorithm, this technique can also provide quantitatively accurate fluorescence images. Finally, the temperature sensitive agents can be modified to target molecular pathways and processes associated with many diseases and hence, TM-FT technique can provide a suitable platform for true molecular in vivo imaging. (more...)

Proteins have found utility for numerous commercial and clinical purposes, including use in biochemical and chemical processes, and as agents for the treatment and prevention of human and veterinary disease. A major challenge associated with the use of proteins is their inherent instability. Many proteins rapidly degrade in response to "environmental stresses," such as changes in temperature, pH, light, and desiccation, which has implications for their production, transport, use and storage. Attachment of poly(ethylene glycol) to therapeutic proteins, a process commonly referred to as PEGylation, has been used successfully to increase their stability in vivo by reducing both protease degradation and renal clearance. However, PEGylation does not necessarily increase protein stability in response to environmental stresses. The development of a technology that enhances the stability of proteins to such stresses would dramatically increase the number of proteins that could be used commercially, reduce costs associated with protein production, storage and transportation, and increase protein shelf-life. (more...)

Investment in biological research has yielded a wealth of knowledge on cellular protein function and interaction. The high level of specificity between protein interactions has drawn considerable attention to their potential as therapeutics for human diseases. However, the delivery of proteins as therapeutics is troublesome due to the degradative environment of the plasma and their inability to pass the cellular membrane. Thus, a method of directly delivering proteins to the cytosol of cells holds tremendous potential in therapeutic and diagnostic applications. (more...)

Although significant efforts have been devoted to bridging the gap between synthetic nanomaterials and viable biologics, development of a bio-mimetic delivery vehicle has remained elusive. Challenges include the limited ability to reproduce a cell’s complex membrane makeup on a nanoscale substrate and the fact that most bioconjugation techniques lead to protein denaturation. Efforts to extend nanoparticle residence time in vivo have inspired a variety of strategies to bypass macrophage uptake and systemic clearance. However, none of these have been able to recapitulate what nature has already evolved as its’ own long-circulating delivery vehicles—the red blood cell (RBC). (more...)

Mesoporous silica nanoparticles (MSNs) are non-toxic, endocytoseable nanomaterials that may be used to carry and mediate release of cargoes such as drugs to targeted tissues and cells. A vast array of methods from pH to light have been used to control the nanovalves on the particles that trap and release cargos within the pores. Magnetic nanocrystals (NCs) have previously been used in biomedical applications both for their usefulness in inducing hyperthermic effects when placed in a magnetic field and for their MRI imaging capabilities. Zinc-doped iron oxide NCs are particularly well-suited for these purposes. The combination of these two technologies yields a novel approach to drug delivery whereby zinc NCs are used to actuate MSN cargo distribution. (more...)

Chronic diseases often require long-term treatment strategies that rely on repeated injections.  These delivery mechanisms, characterized by decreased bioavailability and highly variable drug exposure, constitute significant inconvenience and cost to patients by requiring frequent office visits and increasing potential complications from frequent injections.  For example, treatment of advanced macular degeneration (AMD) requires injections of anti-VEGF proteins into the eye once every four weeks, potentially leading to complications such as retinal detachment and tearing.  These limitations have spurred efforts to create new platforms for longer-term, constant delivery of therapeutics in the body, such as osmotic pumps and microparticle delivery systems.  These systems currently offer sustained release of therapeutics on the order of several weeks.  However, while the current offerings are effective in the release of small-molecule therapeutics, their ability to sustain longer-term, controlled release of large protein-based biologics is severely limited. (more...)

The invention discloses a magnetic navigation system and navigable capsules that are useful for remote-controlled imaging, biopsy, and programmable drug release within the body of an animal. The system includes a capsule dimensioned and shaped to move within the body; an anisotropic magnetic component coupled to the capsule to orient it relative to an applied magnetic field; a detector to determine the location of the capsule within the body; and a magnetic field generating system external to the body that is responsive to the detected location of the capsule. The detector senses the position of the capsule and the feedback of the position information is utilized for controlling the magnetic field generating system to guide the capsule as it moves within the body. The capsule can carry devices for imaging, biopsy, and/or drug release. (more...)

Use of synthetic nucleic acids to manipulate gene function has become a powerful tool for both basic research and therapeutics.  Silencing disease targets by RNA interference is a promising approach to drug development, and various experimental RNA therapies are currently in clinical development by both small and large biotechnology companies.  miRNAs are also being developed for disease treatment and diagnosis.  However, lack of specifically targeted, efficient and safe vehicles for systemic delivery of small RNA payloads in vivo is a serious challenge.  Synthetic nucleic acids face a number of physiological barriers in the bloodstream, and their intracellular uptake is hampered by the fact that they are highly charged and have much larger molecular wieght than small-molecule drugs.  Current strategies to circumvent these problems includes local administration, chemical modifications of nucleic acids, viral delivery vectors, lipid-based delivery systems, polymer-based delivery systems and nanoparticle encapsulation.  These methods have serious flaws including toxicity, inummue effects, non-selectively and high cost of manufacturing.  Therefore, novel ways to deliver synthetic nucleic acids for use in humans and experimental animal models are sorely needed. (more...)

Midazolam has previously been administered via a variety of routes, including the intranasal route, for the management of acute seizures. UC Davis researchers have demonstrated in rodent chemoconvulsant models that inhaled intrapulmonary (nebulized) midazolam can protect against seizures more rapidly and more potently than when administered by other routes. The lung is highly vascularized and the thin alveolar epithelium represents a large absorptive surface. Blood exiting the lung is delivered directly to the brain so that the seizure protection conferred by intrapulmonary midazolam occurs with very short latency. Unexpectedly, midazolam delivered via the lung is more potent than when administered by other routes, including intravenously. (more...)

The rapid progress of nanotechnology in the past decade has fueled a growing interest in polymeric biomaterials that can be remotely disassembled in a controlled fashion upon an external stimulus but otherwise stable under physiological conditions. Various internal and external stimuli, such as pH are being explored.Tissue homeostasis of pH, enzymes, reactive oxygen species and transition metals are highly regulated processes that are altered in pathological states. Mildly acidic pH and mildly oxidative environments are common in metabolic disorders such as cancer. pH-activation has long been a useful tool for differentiating between healthy and disease-state tissue in the pharmaceutical industry. Active targeting exploits atypical extra and intra cellular microenvironments and other physiological characteristics to distinguish between targeted and untargeted tissue. (more...)

An extracellular matrix (ECM) that directs cell behavior and diminishes the chance of an immune response has been developed by researchers at the University of California, Davis.  The invention at issue is a controlled means of depositing a mesenchymal stem cell-secreted extracellular matrix on polymeric implants of any size and geometry.  The ECM is produced by cells on tissue culture plastic under controlled conditions and then decellularized.  The ECM produced on the tissue culture plastic can be reset on other substrates in a controlled manner.  This creates a powerful tool to coat any polymeric implant with an engineered ECM without requiring cells to deposit the ECM on the substrate by culturing for prolonged durations. (more...)

Recent efforts involving bactericides have been focused on ways to aid in the delivery of this material to sites that can benefit from its application. Incorporating antimicrobial materials into bandages for use in wound and burn treatment and into membranes for water purification are some of the attractive opportunities for these materials. (more...)

Researchers at the University of California, Irvine have developed a novel method to continuously pattern nanofibers on 2D and 3D substrates. A unique polymer ink formulation provides the right balance of viscosity and elasticity necessary to enable controlled, seamless near-field electrospinning of nanofibers at very low voltages. (more...)

In addition to their vast therapeutic potential in various neurological disorders, stem cells are also being developed for in vitro disease modeling and drug screening purposes. In vitro recapitulation of developmental differentiation processes permits the generation of specific neural cell types from pluripotent stem cell sources. For example, iPS cells from patients would allow the generation of patient-specific neural cell subtypes for disease modeling, target identification, drug screening and toxicity testing. Such approaches are anticipated to streamline drug development due to the use of more relevant human models instead of animal models.   While some cell types and sources have been identified as being potentially useful for these applications, their efficacy has not been proven and questions about their efficacy and safety still remain unanswered. Currently there is a need for advanced tools that would enable selection and generation of useful cell types for transplantation, and generation of cellular model systems for human diseases.   DESCRIPTION: UCSF investigators have discovered a highly efficient method of differentiating medial ganglionic eminence (MGE) cells from human iPS cells and embryonic stem cell sources. MGE cells are the precursors to forebrain inhibitory neurons that, when impaired, play a role in several diseases including epilepsy, Parkinson’s, Alzheimer’s, autism, schizophrenia, neuropathic pain and spasticity. The investigators’ prior work has shown that MGE cells possess several advantageous properties that would make them useful for treating neurological diseases, namely Parkinson’s disease and epilepsy, see references 1-8, below.   Recently, they have devised a robust method for generating MGE cells from iPS cell sources or embryonic stem cell sources, which consists of simple steps that do not require genetic engineering. The yield is close to 100% efficiency, which is a ten-fold improvement over currently available methods.   Ongoing work is focused on testing therapeutic efficacy of iPS-derived MGE cells in several animal disease models.  (more...)

A novel method for the production of emulsions and dispersions, directed to methods for the formation of colloidal suspensions. These suspensions are formed with or without mechanical action and without surfactants, polymers, or stabilizing agents. (more...)

Although combination therapies are routinely used to treat patients, the approach is challenged by the different therapeutic indices, cellular uptake mechanisms, and in-vivo clearance time of the combined drugs. In sum, the ability to maximize the efficacy of one drug is compromised by the use of many. A method to precisely control the delivery of defined ratios of multiple drugs may allow one to optimize combination therapeutic regimens. (more...)

Researchers at the University of California, Irvine have developed a novel microfluidic device that is capable of encapsulating cells at a very high efficiency. The device integrates impedance measurement with a novel on-demand droplet generation process to enable the selective generation of droplets that contain encapsulated cells only when a cell is present. This ensures that a high percentage of cells are encapsulated rather than droplets that do not contain cells. The device consists of two main components – the impedance sensor and the on-demand droplet generator. When the sensing electrodes of the impedance sensor detects a change in impedance caused by a cell, the cell is coupled with a droplet. (more...)

UC San Diego researchers have developed novel non-peptoid transport molecules that, when coupled to a "cargo" such as an antibiotic or a fluorophore, facilitate the crossing of the cargo across cell membranes into the cytoplasm. A key feature of these transport molecules is their unique three-dimensional structure, which is non-linear and contains peripheral guanidine moieties. Through specific linkers designed by UC San Diego scientists, it is possible to attach a variety of cargo molecules to the transporters via a cleavable covalent bond. Unlike peptide-based molecular transporters, these molecules are non-toxic, non-antigenic, resistant to degradation, and highly efficient in crossing cell membranes, with or without the cargo. They are also easy and inexpensive to synthesize, and can be uniquely adapted to specific types of cargo. (more...)

Researchers at the University of California Davis have developed and tested novel compounds useful for treating Osteoporosis, promoting bone fracture healing, and improving pro-engraftment of stem cells to bone.  (more...)

Nanoparticles capable of reversible changes in morphology in response to specific stimuli are expected to have broad utility in designing targeted drug-delivery, detection strategies, self-healing materials, and templates for hierarchical directed assembly. While there are several elegant examples of stimuli-responsive soft nanoparticles, programmable materials with the requisite shape-change properties remain elusive. (more...)

Integrin plays a key role in the angiogenesis and metastasis of human tumors. αvβ3 integrin binding ligands have value in cancer diagnostic imaging and targeted therapy. The RGD motif binds to several integins, including αvβ3, αIIbβ3, αvβ5, and α5β1. It is known that amino acids lateral to RGD affect RGD binding specificity to different integrins. Researchers at the University of California Davis have discovered a novel RGD-containing peptide useful in cancer imaging and as a targeted-therapy ligand. (more...)

High molecular weight biomolecules, such as certain proteins and nucleic acids, display therapeutic potential. However, their limited cellular uptake hampers utilization and has prompted the development of delivery technologies. Lysosomal storage disorders are the best studied examples of genetic diseases caused by missing intracellular enzymes. The most direct remedy involves the injection of recombinant enzymes, which are targeted to lysosomes by cell surface mannose-6-phosphate receptors. While this approach restores enzyme activity in many tissues, it is compromised by (i) inefficient delivery to diverse cell types, (ii) delivery only to the lysosomal compartment of cells, and (iii) the inability to cross the blood-brain-barrier to reach neural tissues. (more...)

The present invention relates to a system and method to provide item-level monitoring of environmental quantities including, but not limited to, temperature, humidity, air gas components, radiation. (more...)

p53 plays a pivotal role towards inhibition of tumor progression, survival, and metastasis. As such, p53 has been a central target in tumor therapy and in particular, gene therapy targeting cancer. Recent efforts in utilizing p53 as a gene therapy show varying efficacies. The primary cause for these inconsistencies appears to be the inherit obstacles which gene therapy must overcome. Current approaches in gene therapy are hampered by inefficient delivery, toxicity concerns, immunogenicity, proper gene function, and limited expression of the gene delivered. Due to its potent tumor suppressing capacity, however, gene therapy with p53 continues to be one of the more sought after tumor therapies. (more...)

Drug target identification (ID) is to search for a protein or to fingerprint a domain of a protein, with which a pharmaceutical drug specifically interacts; therefore this process provides critical information on the therapeutic mechanism of a drug and also potential side effects. Drug target identification is a rate-limiting step in drug discovery and drug development. Current methods are unsatisfactory because they either cannot use a drug in its native form, require a large quantity of a target protein, or rely on overt biological effects. Therefore, it is very desirable to develop a target identification method that overcomes these limitations and advances the rate-limiting step in both drug discovery and chemical genetics research. (more...)

Treatment for tuberculosis infection involves multiple drug therapy using combinations of rifampin, isoniazid, pyrazinamide, and ethambutol. However, rifampin is a highly toxic antibiotic that induces hepatitis, thrombocytopenia, bullous skin rashes and other injury. Drug toxicity is caused by free rifampin in the blood stream that failed to bind human serum albumin (HSA) to which it binds non-specifically . (more...)

Transferrin (Tf) is a critical iron transport protein found in the blood. Tf loaded with iron binds to the cell surface Tf receptor (TfR) and is taken into the cell. Once inside the cell, Tf releases its iron load and both Tf and TfR are then recycled back to the cell surface and Tf is released into the extracellular space. Due to the observation that TfR is overexpressed in a broad range of cancers, Tf is currently being investigated in clinical trials as a potential drug carrier to allow specific targeting to cancer cells. It has been shown previously that the duration of Tf cellular trafficking is correlated with effectiveness of drug delivery. Therefore, increasing the cellular association of Tf should result in more efficient drug delivery. (more...)

Polymeric vesicles are a new class of nanoscale self-assembled materials that show great promise in drug delivery applications. Compared to liposomes, polypeptide vesicles have increased stability and can respond to external stimuli. (more...)

The main obstacle facing the use of gene therapy as a successful therapeutic modality for humans is the inability to accurately target vectors to organs and cells. Adenoviral and adeno-associated vectors have been associated with mutagenesis and liver toxicity. Other vectors have suffered from ineffective entry and failure to provide stable long term expression. (more...)

UC San Diego researchers have developed an extensive platform of technologies based on porous silicon and/or polymeric nano-particles (“smart dust”). This platform encompasses multiple uses of nano-scale particles of porous silicon photonic crystals and takes advantage of the optical properties and other physical characteristics of this material. (more...)

Lipids and liposomes are widely used for nucleic acid, protein and drug delivery into cells and several kits are commercially available, especially for DNA and RNA transfer. However, this non-selective lipid mediated transfection technology can be greatly improved with the addition of protein particles obtained from a defined viral preparation. (more...)

A UCSD researcher has developed a new macromolecular carrier having hundreds of leashes for readily attaching imaging agents and substrates. The attached substrate directs the carrier to specific tissues so that the attached imaging agent can affect its function in a tissue specific manner. When suitably derivatized, the carrier can be used in a tissue-specific manner for magnetic resonance imaging, computer tomographic imaging or scintigraphic imaging. This technology has been shown to exhibit excellent tissue-specific delivery of payload as demonstrated in animals and humans, is inexpensive to manufacture, and is non-toxic to humans. It has also been shown in animal tests to be a CT blood pool contrast agent with long intra-vascular dwell time. The patent - US 6,409,990 - is available for licensing for use in certain tissue types and imaging methods. (more...)

Delivery of molecules across cellular membranes is difficult for many classes of molecules with therapeutic potential. (more...)

The control of materials in microscale quantities is of interest in a wide range of fields. A particular area of microscale material control that has drawn much attention is microfluidics. Heating techniques developed for use in microfluidic networks are problematic due to the requirement for efficiency in the localized heating of the individual droplets with minimal heat transfer to the surrounding area. (more...)

Many current nanoparticles used for drug delivery and sensing are solid. This technology describes the synthesis of hollow nanospheres and their uses for life science applications. (more...)

Researchers at the University of California, Irvine have developed novel polydimethylsiloxane shelled microbubbles that may be functionalized with a variety of ligands to selectively target treatment or diagnosis. These microbubbles may be used as a stand-alone application in biological applications such as medical imaging and drug delivery. (more...)

University researchers have invented an approach to develop compounds the use of which would lessen the need for surgical placement and replacement of intravitreal implants for treating chronic vitreoretinal diseases. Frequent injections of therapies can lead to retinal detachment and endophthalmitis, and are extremely inconvenient to the patient. By developing a compound that has the property of being intravitreally injectable and long-acting, University researchers have come up with a way to administer therapy to the eye that does not require surgery or frequent injections. Animal studies have confirmed that the half-life of a therapeutic may be extended to between 8 to 20 weeks, or more. (more...)

UC San Diego researchers have developed a new nanotechnology platform called "smart dust" with state-of-the art applications in almost every field of use, ranging from biological sensing and screening to communications technology. The invention utilizes micron-sized particles of silicon that have been etched and then chemically modified in such a way that each individual particle has its own addressable identity. This feature allows one to use thousands of particles together, each with its own tag, for high-sensitivity chemical or biological sensing, diagnostics, and low- and high-throughput screening of biomolecular compounds. The method does not require the use of fluorescent tags, but could be used in conjunction with them. (more...)

In the search for in vitro cell lines that can be continuously cultured, neurons have been amongst the most intractable. This was presaged by their behavior in situ; relative to other tissues, a limited number of cells are reported to divide. Excluding immortalized cell lines, there is a dearth of well-characterized, established cell lines from central nervous system (CNS) and neuronal tissues and those in existence are often limited in their ability to mimic the biology of the primary neurons from which they were originally established. Effective drug discovery screening programs require the use of primary cultures that: are phenotypically representative of the primary cells from which they were derived can be used to generate continuously proliferating cultures of specific neuronal cell lines Cell lines that meet these criteria will prove invaluable for neurobiological studies, CNS drug discovery efforts and may significantly change the landscape for therapeutics. (more...)

Target-selective drug delivery remains a challenge for various therapeutic applications and particularly for cancer. Current targeting strategies include formulation and encapsulation for preferential release in the acidic tumor environment as well as covalent conjugation via linkers sensitive to pH, to oxygen levels, or to disease-specific enzymes. These approaches have been limited by: Stringent requirements on linkable drugs and carriers.Inflexible rates of release.Insufficient target/tumor-specificity of relevant enzymes. (more...)

Multifunctional nanoparticles have the potential to deliver both therapeutics and diagnostics to tissues simultaneously using a single nanodevice. To date, several types of hybrid nanosystems have been developed and used in vitro for magnetic cell separation and targeting. However, the in vivo utility of these nanocomposites may be limited due to poor stability or short systemic circulation times. Furthermore, existing technologies do not adequately allow for co-delivery of a therapeutic and an agent enabling advanced diagnostic imaging. (more...)

UCSF investigators have developed a novel targeted pro-drug technology that can selectively deliver a chemotherapeutic payload to cells in areas of high concentrations of endogenous free ferrous iron. The pro-drug can be conjugated to a variety of existing and novel pharmacologically active compounds to increase their therapeutic window and lower systemic toxicity by increasing the selectivity of their delivery. Applications include therapies for cancer and malaria and as imaging agents.  (more...)

Stem cell therapy holds the promise of treating a variety of human conditions such as diabetes, cancer, and neurological diseases. It is thought that stem cells could be especially useful for neurological diseases and disorders as the brain has a limited capacity for self-repair and regeneration. Additionally, there are no effective long-term treatments or cures for certain brain disorders or neurodegenerative diseases such as Alzheimers, Parkinsons, and Huntingtons disease. Collectively, these conditions represent a significant unmet medical need. Regenerative approaches for the brain have the potential to address the cause of the disease, rather than simply addressing symptoms, by repairing or reversing the disease state. However, because the underlying causes of the brain diseases are diverse, several different approaches are required to adequately address the various causes. Some examples include cell replacement for dead or lost cells, modification and augmentation of faulty circuitry, and delivery of therapeutics to poorly functioning cells for protection from degeneration. While some cell types and sources have been identified (e.g. fetal porcine ganglionic eminence cells and dopaminergic neurons), their efficacy has not been proven. In addition, questions remain about whether such cells will form brain tumors in vivo, persist for long periods of time, or will work in aged brains, when people are most susceptible to neurological disease. There is a need in the field for the identification of cell types that can be applied in many disease contexts. DESCRIPTION: UCSF Researchers have discovered that a population of neural precursors, called medial ganglionic eminence (MGE cells), possess several advantageous properties that would make them useful for a number of neurological diseases. When injected into various regions of the brain, MGE cells disperse homogenously over long distances, form inhibitory interneurons (GABAergic neurons), integrate to form functional connections with endogenous circuits, and influence the activity of surrounding neurons. Interestingly, MGE cells behave this way in postnatal brains, suggesting they could work in aged brains. By virtue of these qualities, it is thought that MGE cells can be used to treat several brain diseases via cell replacement, modification of endogenous circuitry, or by delivery of therapeutics. To support this assertion, the researchers have performed proof-of-principle experiments in rodent models of epilepsy and Parkinsons disease. Implantation of MGE cells into the cortex of postnatal brains in rodent models of epilepsy was shown to significantly reduce seizure symptoms. MGE cells achieved this via both GABAergic modulation of electrical activity and cellular replacement of inhibitory neurons. Further, implantation of MGE cells into the striatum of 6-OHDA rodents was shown to ameliorate symptoms of Parkinsons disease via modulation of faulty circuitry resulting from degeneration of dopaminergic input. Based on these initial data, the researchers envision that MGE cells could be applied to additional brain disorders. Indeed, preliminary data suggest that MGE cells could be used to treat diseases caused by aberrations in the organization or activity of the brain, such as stroke, cerebral palsy, and Schizophrenia. MGE cells can regulate a process known as experience-dependent plasticity, which allows for changes to be made in the wiring or activity of neurons. Selective reactivation of this process in the adult brain could result in functional reorganization that could fix or compensate for any lack of function and alleviate the symptoms of disease. Preliminary data also suggest that MGE cells can be used to treat spasticity caused by spinal cord injury. It is thought that spasticity results hyperactivity spinal circuitry. MGE cells grafted into the spinal cord are expected to integrate and produce factors that inhibit local circuitry to reduce spasticity. Experimental testing in related animal disease models is underway. (more...)

Her2/neu is over-expressed in various types of tumor cells, including 20-30% of breast cancers, adenocarcinomas of the ovary, salivary gland, stomach and kidney, colon cancer, and non-small cell lung cancer. Passive immunotherapeutics like Herceptin control and prevent further tumor cell growth. Unlike active immunotherapeutics, Herceptin does not mediate the immunological cellular destruction. Active immunotherapeutics such as vaccines elicit T helper-1 (Th1) and Cytotoxic T lymphocytes (CTL) biased immune responses and are generally observed for proteins expressed in the intracellular compartment, and less prominently with extracellular or secreted proteins. Rapid degradation of a protein containing polyepitopes can contribute to establishing a bias in the immune response, facilitate antigen presentation and, perhaps assist in establishing specificity of the immune response. This type of immunological response should result in immunological cellular destruction. (more...)

Options for successful repair of peripheral nerves after traumatic injury remain suboptimal. Current strategies are limited to transfer of donor nerves from functional areas, with substantial donor-site morbidity and variable outcomes. The development of tissue-engineering strategies offers significant hope to patients facing functional impairment and cosmetic problems after such injuries. Tissue-engineered constructs used to bridge nerve gaps have the potential to improve options for the regeneration of peripheral nerves after transaction and the restoration of function. However these constructs must be rendered bioactive to be effective. One method of creating bioactive constructs involves the delivery of growth factors necessary for nerve repair and development. (more...)

BRCA2/RAD5 1 interaction is essential for DNA repair mechanisms and play significant role in tumor resistance to irradiation and chemotherapy treatments. Effective strategies to selectively interfere with BRCA2/RAD5 1 interaction in the context of treatment and chemoprevention of neoplastic diseases are described. (more...)

University of California researchers are investigating a protein scaffold system for molecular transport, namely, the E2 protein of Bacillus stearothermophilus in the pyruvate dehydrogenase complex. This model system has many features that make it attractive as a generalizable scaffold for drug delivery. Although it is a large complex, it self-assembles from smaller subunits that are easily heterologously expressed in E. coli. Since it is derived from a thermophilic organism, it is quite stable. In contrast to other self-assembling spherical complexes (such as icosahedral viral capsids) the core can accommodate large foreign peptides and proteins that are genetically engineered to the surface while retaining its self-assembling capabilities. This allows targeting regions to be easily incorporated into the system.UC researchers will engineer self-assembled protein complexes to encapsulate and transport drug molecules with varying chemical properties. To engineer this complex for solubilization and delivery of drug molecules, the characteristics of the protein will be investigated. Molecular modeling of the structure will aid the selection of amino acid targets. UC researchers will also test cell targeting and internalization by peptides and proteins. One important advantage of this system over other caged protein systems for drug delivery is the ability to genetically use foreign peptides and proteins without critically affecting the self-assembly behavior of the icosahedral core. UC researchers will also determine the molecular parameters in the self-assembly of the engineered protein scaffold. Understanding the reasons behind this protein self-assembly and stability is key to the development of an engineered complex based on human E2. This aim will investigate the important interactions which promote the self-assembly and themostability of the E2 protein. (more...)

Large scale confinement chambers have been created in the past using traditional glass-blowing techniques. However, conventional glass-blowing can only be used to create large components and requires the components to be made one at a time. Micro-glass spheres have previously been fabricated by letting glass particles fall through a temperature-controlled drop tower. While it is possible to create hollow spheres by introducing a blowing agent in the glass, these micro-spheres are not attached to a substrate and are therefore difficult to integrate with micro-machined components on a wafer. (more...)

The ability to deliver drugs locally to the site of need and over a prolonged period of time is important as a therapeutic method for many ailments and diseases. Many drugs are more effective if delivered at a specific site since they can be delivered in concentrated dosages at the point of interest, while maintaining an overall low dosage within the total body. Some drugs require delivery in places that are inconvenient for injection. For example, the highly invasive nature of the treatment and limitations in controlling an effective drug concentration in the eye for age related macular degeneration (AMD) over a prolonged period of time still leave these delivery methods far from ideal. Small, programmable drug delivery implants would be a highly valuable alternative. The current state of art does not provide a satisfactory way to construct a small device that can deliver a time dependent profile of drug dosing. A device that can be readily constructed to produce a desired time dosing profile would be desirable. (more...)

  Normal 0 0 1 117 672 UC Berkeley 5 1 825 11.1282 0 0 0 This invention consists of a bioengineering and surgical method for the treatment of cardiac injuries by mechanical stabilization of the injured region. The technique involves the injection or implantation of a material into the border zone of the injury or infarct. When implanted, the material will integrate into the host myocardium and share the mechanical loads during the cardiac cycle, reduce the fiber stresses in the infarct zone, and prevent progression to congestive heart failure. In addition the material can be used as a carrier for the addition of transplanted cells for improved rates of healing. The combined effect of matrix-associated reduction in fiber stress and enhanced transplanted cell survival has the potential to be a novel therapy to restore cardiac function and reduce heart failure. (more...)

Attempts to transplant organ tissues into genetically dissimilar hosts without immunosuppression are generally defeated by the immune system of the host. Protective barrier coatings to isolate the transplant tissues from the host immune system have been attempted but coating materials were incompatible with the host system or were unsuitable. This patent portfolio describes methods and techniques for coating biological materials such as tissues, cells and cell lines with a continuous, uniform, semi-permeable and bio-compatible coating. The novel coating is non-fibrogenic and does not cause immune reactions destructive to the transplant functionality. In addition, UC Davis researchers have developed an apparatus and method for coating these biological materials and other solid and semi-solid particles to form smooth and uniform size microcapsules. (more...)

Researchers at the University of California, Davis have developed transgenic mouse models that constitutively express B cell Activating Factor (BAFF) in the Tumor Necrosis Factor (TNF) family, and Green Fluorescent Protein (GFP) under the control of Glial Fibrillary Acidic Protein (GFAP) promoter in astrocytes. (more...)

In 2007, diabetes accounted for $174 billion in health-care costs, with 20.8 million Americans diagnosed with this disease. Type I diabetes comprises up to 10% of diabetes mellitus cases in North America. Intensive insulin therapy can help reduce the risks of developing complications like neuropathy, nephropathy and ketoacidosis, but it requires three or more insulin injections or use of an external insulin infusion pump. We currently have excellent insulin infusion pumps, and continuous glucose sensors are now sufficiently accurate to be used to regulate insulin delivery. What is missing is a program (algorithm) to regulate insulin delivery based on the signal from a continuous glucose sensor. In addition, the risk of nocturnal hypoglycemia is still high. (more...)

In the last few years a very large research effort has been devoted to developing new compounds that are carriers of DNA and other macromolecules into human cells. Compounds composed of DNA and cationic liposomes (CL-DNA complexes) are especially promising vectors for non-viral gene-therapy applications. These compounds have numerous advantages over viral methods, such as their lower toxicity, simpler preparation, lack of immune response from the body, and ability to carry large pieces of DNA. (more...)