Brief description not available

Brief description not available

This invention is a nanostraw device that is built upon microdevice technology for oral drug delivery. It is the first example of a microdevice for oral drug delivery, with the drug sealed in by a semi-permeable membrane for (1) in-solution drug loading, and tunable drug release, (2) increased bioadhesion for prolonged drug exposure, and (3) protection of drug from outside biomolecules.

This invention describes a first-of-a-kind methodology using micro- and nanofabrication techniques to create polymeric microscale devices that are asymmetrically coated with nanowires. The nanowire coating provides an inherent high-throughput, low-waste drug loading mechanism, enhanced cytoadhesion, and may potentially interact with epithelial tissue to enhance drug permeation.

This invention describes an orientation-independent device that can create bright and highly localized signal enhancement during magnetic resonance imaging.

This invention includes the design and use of protease imaging reporters which can be detected in deep tissue. These can be used to monitor the effects of protease inhibitors, proteases and protease mediated processes including apoptosis related to the treatment of disease states such as cancer.

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.

  Background: Polymeric delivery of chemotherapeutics has successfully improved cancer treatments over the past two decades. Polymers well-suited for drug delivery applications confer high solubility, long circulation half-life, biocompatibility, low toxicity, and high accumulation at tumor sites. Research into polymer parameters affecting these criteria has guided drug developers toward optimally sized polymers and the exploration of polymer architectures. Recently, increased polymer branching has been shown to increase drug circulation times and decrease elimination by the kidney. A novel branched polymer system and its simple synthesis comprise this drug delivery advancement.   Summary: UCSF researchers have discovered a PEGylated polymer system that is superior to known PEGylation technologies. This system consists of a polyester comb branched-PEG hybrid characterized by a highly branched polymer structure in which the branches detach hydrolytically. Biodistribution studies showed that, in comparison with linear polymers of the same molecular weight, comb branched polymers were able to escape kidney clearance, extending its blood circulation half life. High levels of tumor accumulation were found for comb branched polymers with molecular weights as low as 44kDa in mice bearing subcutaneous C26 colon carcinoma. The polymers degrade to lower molecular weights at both normal physiological pH and mildly acidic pH, enabling complete clearance by renal excretion and minimizing residual polymer buildup in kidneys and other organs.   Historically PEGylation has been associated with several manufacturing disadvantages, none of which handicap the comb branched polymer synthesis. PEGylated dendrimers are typically synthesized by coupling activated PEG chains to dendrimer cores, whose synthesis require multiple steps. To reduce the number of synthetic steps to reach a high molecular weight, expensive functionalized PEGs are required. Alternatively, synthesis of PEG dendrimers is also possible through radical polymerization using core initiators. While this yields polymers with high molecular weight and low polydispersity, these core intiators are difficult to synthesize or not biodegradable. In contrast, UCSF's comb branched polymers are easily synthesized using inexpensive and commercially available starting materials. The resulting polymer has a polymer distribution index of less than 1.15, indicating the synthesis is well-controlled. Its narrow polydispersity, together with consistent drug loading, leads to reproducible pharmacokinetic behavior. The synthetic advantages and improved pharmacokinetic properties of the comb branched polymer system make them ideal for the next generation of chemotherapeutics.  

UCSF cardiologists have developed a novel topical anesthetic composition that facilitates radial artery cannulation. This composition can be delivered either as a topical cream or through a transdermal patch and can be co-marketed with radial catheterization sheaths and cannulaes to increase product appeal to clinical users. In clinical trials, this novel composition causes local increase of the arterial diamter (by 25% or more for at least 30 minutes) and provides local anesthesia in the patient, without inducing undesirable systemic effects, thus enabling clinicians to insert radial arterial catheters with greater ease, reduce the risk of spasm, and reduce pain experienced by patients undergoing this procedure. 

BACKGROUND:   Liposomes have been used in many drug, nutritional, and cosmetic delivery applications due to their unique properties that mimic the phospholipid bilayer of cell membranes. In all of their applications, liposome stability is crucial for efficient delivery stable liposomes mimimize leakage and loss of the payload. Sterols such as cholesterol have been proven to to greatly improve liposome stabilization. Consequently, cholesterol is widely used in liposome formulations. Sterols, as phytosterols, are also used in a variety of nutritional products to reduce cholesterol levels in humans. UNMET NEED: When liposomes composed of free cholesterol and phospholipids are combined with biological fluids containing biological lipids and serum, cholesterol rapidly transfers out of the liposome into the biological lipids. This loss of cholesterol from the liposome results in decreased liposome stability and the subsequent leakage or loss of the encapsulated payload. Additionally, serum lipoproteins absorb free cholesterol, further increasing the rate of cholesterol loss from the liposome. Efforts to solve this problem have led to the development of water soluble sterol derivatives as well as hydrophobic sterols. However, neither have proven to be suitable for improving liposome stability. A new technology is needed that will allow liposomes with high amounts of sterols to remain stable when exposed to biological fluids.   SUMMARY: Scientists at UCSF have developed sterol derivatives that improve liposome stability both in vitro and in vivo. These derivatives can be incorporated into liposome formulations in the high amounts necessary to produce a stabilizing effect, and are resistant to transfer out of the liposome into biological fluid components. Cholesterol transfer out of a liposome in in a lipid laden environment typically occurs with a half-life of two hours, whereas the transfer of the UCSF sterol derivatives under the same conditions is undetectable after eight hours. Furthermore, liposomes containing UCSF sterol derivatives have demonstrated 80% less leakage in serum than liposomes containing free cholesterol.  As an example of an oncology application, UCSF sterol-containing liposomes encapsulating doxorubicin showed equivalent therapeutic effect when compared to DoxilTM in a mouse cancer model.  In an infectious disease application, UCSF sterol-containing liposomes encapsulating amphotericin B showed lower toxicity and improved activity against a panel of fungi compared to AmBisomeTM.