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Engineering Protein Nanoparticles for Enhanced Vaccine Delivery

A revolutionary vaccine platform enabling the co-delivery of multiple toll-like receptor agonists and an antigen for potent immune responses.

Polyphenol Infusions to Improve Gastro-Intestinal Stability of Probiotics

Researchers at the University of California, Davis have developed a method for improving probiotic resistance to conditions in the gastrointestinal tract by simultaneously delivering probiotics and extracts of fruit and vegetables rich in polyphenols which fight inflammation and improves health in the GI tract.

Polymeric Vectors For mRNA Delivery

A novel dendronized polypeptide architecture for efficient and safe mRNA delivery, suitable for anti-tumor immunotherapy.

Wearable Bioelectronics for Programmable Delivery of Therapy

Precise control of wound healing depends on physician’s evaluation, experience. Physicians provide conditions and time for body to either heal itself, or to accept and heal around direct transplantations, and their practice relies a lot on passive recovery. Slow healing of recalcitrant wounds is a known persistent problem, with incomplete healing, scarring, and abnormal tissue regeneration. 23% of military blast and burn wounds do not close, affecting a patient’s bone, skin, nerves. 64% of military trauma have abnormal bone growth into soft tissue. While newer static approaches have demonstrated enhanced growth of non-regenerative tissue, they do not adapt to the changing state of wound, thus resulting in limited efficacy.

Bioelectronic Smart Bandage For Controlling Wound pH through Proton Delivery

Precise control of wound healing depends on physician’s evaluation, experience. Physicians provide conditions and time for body to either heal itself, or to accept and heal around direct transplantations, and their practice relies a lot on passive recovery. Slow healing of recalcitrant wounds is a known persistent problem, with incomplete healing, scarring, and abnormal tissue regeneration. 23% of military blast and burn wounds do not close, affecting a patient’s bone, skin, nerves. 64% of military trauma have abnormal bone growth into soft tissue. While newer static approaches have demonstrated enhanced growth of non-regenerative tissue, they do not adapt to the changing state of wound, thus resulting in limited efficacy.

Inverse Design and Fabrication of Controlled Release Structures

Researchers at the University of California, Davis have developed an algorithm for designing and identifying complex structures having custom release profiles for controlled drug delivery.

Site Directed DNA Editing with Adenosine Deaminases that Act on RNA (ADAR) Enzymes

Researchers at the University of California, Davis have developed a method and composition for modifying genetic sequences using Adenosine deaminases that act on RNA (ADARs).

Injectable Hydrogel Used for Sustained Delivery of Vaccine

This technology introduces a novel vaccine delivery system using thermosensitive hydrogels for sustained antigen release, aiming to improve immune response durability and breadth.

Enhanced Nucleic Acid Delivery To Cells

mRNA-based cancer therapies include vaccination via mRNA delivery of tumor neoantigens, delivery of mRNA encoding for immune checkpoint and other protein therapeutics, and induced expression of anticancer surface proteins such as CAR expression in T cells. Success requires transfection of a critical number of immune cells together with appropriate immune-stimulation to effectively drive anti-tumor responses. UC Berkeley researchers have developed an adjuvant-assisted mRNA LNP delivery method that uses mRNA LNP and adjuvant to enhance delivery of nucleic acids to immune cells in vivo and stimulate immune cells. They demonstrated the use of this system to reduce mRNA reporter protein expression in the liver and enhance protein expression in the spleen in mice and also demonstrated this system can be used to genetically engineer T cells by delivering a Cre-recombinase mRNA construct- transfection and editing of approximately 4% of T cells is achieved in vivo. The immune response is superior in our system compared to current, commercial lipid nanoparticle delivery technologies.

Affinity Peptides for Diagnosis and Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 and Zika Virus Infections

Researchers at the University of California, Davis have developed a technology to expedite COVID-19 diagnosis and treatment using viral spike protein (S-protein) targeted peptides Zika virus envelop protein.

Electricity enhanced delivery of drugs into the ureter, renal pelvis, and renal parenchyma

The invention entails a unique catheter device utilizing electromotive drug administration (EMDA) to enhance drug penetrance into tissues of the ureter, renal pelvis, and calyces. By incorporating a conductive wire and fluid delivery system, the catheter enables targeted drug delivery, potentially revolutionizing the treatment of kidney stones, urothelial carcinoma, infections, and inflammation without systemic side effects.

Implantable Prosthetic Valves

The invention pertains to a prosthetic valve featuring a saddle-shaped annulus that synchronously transforms between concave and convex configurations, facilitating seamless opening and closure synchronized with cardiac cycles. Comprising leaflets and support elements, the valve mimics natural heart valve function, enabling effective blood flow regulation and offering versatile deployment options for cardiac and vascular applications.

Growth-accommodating heart valve system

This technology describes a prosthetic heart valve system designed to accommodate the growth of children.

Design Of Functional Protein Materials Based on Beta-Rippled Sheet Architectures

The rippled sheet was proposed by Pauling and Corey as a structural class in 1953. Following approximately a half century of only minimal activity in the field, the experimental foundation began to emerge, with some of the key papers published over the course of the last decade. Researchers at UC Santa Cruz have explored the structure of and have discovered ways to form new beta rippled sheets. 

Novel Solid Lipid Nanoparticle To Improve Heart Cardio Protection

A primary reason behind the lack of progress in heart therapeutics is the inability to use phenotypic human tissue-level approaches to discover novel therapies. In recent years, there have been significant advances in the development microphysiological systems (MPS), which recapitulate organ-level and even organism-level functions.   MPS are quickly becoming representative of the future of disease modeling and drug screening, therefore paving the way for complex in vitro models to dominate the preclinical drug discovery landscape. However, there has yet to be an effective LNP formulation for therapeutic mRNA delivery to the heart. Therefore, despite progress in this area, one of the remaining challenges is to develop a LNP formulation capable of diffusing within human cardiac muscle, transfecting cardiomyocytes, and escaping the endo-lysosome before degradation more efficiently than current strategies. UC Berkeley researchers and others have developed compositions and methods using lipid nanoparticles for delivery of a payload (e.g., messenger RNA (mRNA)) to the heart, for delivery of mRNA for transfection of cells and methods of treatment.

Mitochondria Targeting Photosensitizer for Photodynamic Therapy

Researchers at the University of California, Davis have developed a self-assembling, fibrous photosensitizer that targets mitochondria in tumor cells for destruction via photodynamic therapy with enhanced localization and potency.

(SD2021-154) A new platform for the controlled entrapment and release of molecular cargo

Researchers from UC San Diego have invented a new form of materials, polymer-integrated crystals (PIX), which combine the structural order of protein crystals with the dynamic, stimuli-responsive properties of synthetic polymers. The inventors have shown that the crystallinity, flexibility, and chemical tunability of PIX can be exploited to encapsulate guest proteins with high loading efficiencies. And, the electrostatic host-guest interactions enable reversible, pH-controlled uptake/release of guest proteins as well as the mutual stabilization of the host and the guest, thus creating a uniquely synergistic platform toward the development of functional biomaterials and the controlled delivery of biological macromolecules.

Novel Cell Penetrating Peptide for Drug Delivery

Professor Min Xue and his lab at the University of California, Riverside have developed a novel hydrophilic endocytosis-promoting peptide (EPP6) rich in hydroxyl groups with no positive charge that may be used for drug delivery purposes. This peptide is non-toxic and has been shown to transport a wide array of small-molecule cargos into a diverse panel of cells. It enables oral administration and absorption through the intestinal lining, and crosses the BBB in vivo. UCR EPP6 is advantageous over existing technologies since it is nontoxic, efficiently enables oral absorption and transport across the BBB.  Fig 1: A) Structure of the UCR EPP. B) Confocal images showing that EPP6 was able to transport different cargo molecules into the cells. C) Orally administered EPP6 is absorbed by the intestines, entering the blood circulation and reaching the brain.  

Human Central Nervous System (CNS) Targeting AAV Variants

Researchers at UCSF and UC Berkeley have developed a recombinant adeno-associated virus (rAAV) with an altered capsid protein, where the rAAV exhibits greater ability to infect a central nervous system cell compared to wild-type AAVs. The central nervous system (CNS) comprises a multitude of cell types with diverse functionality and specialization. Dysregulation of neuronal or glial (including microglial) populations has been implicated in multiple disorders, including Alzheimer’s, Parkinson’s, Multiple Sclerosis and Huntington’s disease. AAVs hold tremendous promise as a gene delivery vector to treat such conditions given their reasonable starting efficiency and safety profile. However, challenges in efficient and targeted delivery to specific cell populations make strategies employing these vectors in the CNS particularly challenging. Stage of Research The inventors have developed a recombinant AAV with an altered capsid protein, where the rAAV exhibits greater ability to infect a CNS cell compared to wild-type AAV.

Sildenafil Enables Efficient, Single-Day Hematopoietic Stem Cell Mobilization

Although hematopoietic stem cells (HSCs) are useful in a variety of treatments, HSC donation is a difficult procedure. The original transplantation is commonly extracted from the bone marrow manually, a long and potentially painful procedure. Other techniques for mobilizing HSC to the bloodstream involve a 5-day regimen of G-CSF treatment, that has significant side effects of fatigue, nausea, and bone pain. UC Santa Cruz researchers developed a treatment that allows collection of HSC from blood in a 2-hour treatment using already FDA-approved drugs. This makes both the cost and overall comfort of patient donating HSC’s significantly easier.

(SD2021-089) Unbiased approach for identification of regulators of materials and molecular uptake into cells

A major bottleneck in nanocarrier and macromolecule development for therapeutic delivery is our limited understanding of the processes involved in their uptake into target cells. This includes their active interactions with membrane transporters that co-ordinate cellular uptake and processing. Current strategies to elucidate the mechanism of uptake, such as painstaking manipulation of individual effectors with pharmacological inhibitors or specific genetic knockdowns, are limited in scope and biased towards previously studied pathways or the intuition of the investigators. Furthermore, each of these approaches present significant off-target effects, clouding the outcomes. Methods for intracellular transport of nucleic acids are much sought after in the context of both in vitro delivery reagents and in vivo therapeutics. Recently, we found that micellar assemblies of hundreds of amphiphiles consisting of single-stranded DNA which has been covalently linked to a hydrophobic polymer, referred to as DNA-polymer amphiphile nanoparticles or DPANPs, can readily access the cytosol of cells where they modulate mRNA expression of target genomes without transfection or other helper reagents, making them potential therapeutic nucleic acid carriers. However, despite their effective uptake properties and efficacy in the cytosol, it was unknown how these polyanionic structures can enter cells. Indeed, generally, bottlenecks in understanding and achieving delivery and uptake remain a forefront issue in translatability of macromolecular and nanomaterials-based therapeutics generally, including with respect to nucleic acid therapies. The nature of pooled screening requires amplifying a single ~200nt region per cell, leading to screens that require amplification from tens-to hundreds of micrograms of genomic DNA. Inhibitory effects of high DNA concentration per PCR have led to a variety of solutions, ranging from simply pooling hundreds of PCR reactions to utilizing restriction enzyme sites present in the lentiviral backbone constant regions flanking the sgRNA to perform DNA gel electrophoresis and size selection to remove undesired gDNA. However, these approaches can be both expensive and have significant handling challenges when scaled to large screens.

Sequential Targeting and Crosslinking Nanoparticles for Tackling the Multiple Barriers to Treat Brain Tumors

Researchers at the University of California, Davis have developed an approach to improve drug delivery to tumors and metastases in the brain. Their multi-barrier tackling delivery strategy has worked to efficiently impact brain tumor management while also achieving increased survival times in anti-cancer efficacy.

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