Technologies
Abstract
Hydrogels are the
three-dimensional network of hydrophilic polymers, which have the ability to
imbibe large amount of water inside them. Their soft porous structure makes
them resemble the human tissue and serves as prefect candidate for drug
delivery and tissue engineering applications. Many studies showed the
development of fluorescence based hydrogels for various applications including
sensing and tracking therapeutics in vitro and in vivo. To obtain hydrogels
with fluorescent properties, it is possible to chemically or physically immobilize fluorophores inside the hydrogel matrix. However, these techniques
have several drawbacks; the synthetic routes are complex and tedious, the
fluorophores addition can affect the sought after hydrogel features, such as
biocompatibility and biodegradability, and the resulting hydrogels suffer from
potential leakage and photobleaching of fluorophores.FIU inventors have developed fluorescent hydrogels nanoparticles and microparticles that comprises
cross-linked gels of chitosan, hydroxyethyl cellulose, linseed oil polyol and a
crosslinking agent, such as glutaraldehyde. These particles exhibit
multi-channel fluorescence properties, which makes them a unique imaging agent
having a wide detection limit that is accessible for a variety of
instruments. These particles are useful
for diagnostics and therapeutics purposes including drug delivery, imaging of
drug migration, and selectivity by the tagging or binding of the hydrogel
nanoparticles and microparticles with appropriate antibodies or antigens. They
also can include magnetic nanoparticles, allowing a drug delivery formulation
to possess target specificity combined with in vivo drug monitoring.Benefit
Possess excellent biocompatibility, cell uptake and surface functionalityDo not require any additional fluorescent labelsCan be used with various instrumentsMarket Application
Targeted drug delivery and image-guided therapyBio-sensingIn vivo drug monitoring and diagnosisPublications
Arti Vashist et al. Development of Multifunctional Biopolymeric Auto-Fluorescent Micro-and Nanogels as a Platform for Biomedical Applications. Frontiers in Bioengineering and Biotechnology, 8, p.315. PMID:32426338
Abstract
HIV infection in human cells is either active or a latent.
In most human cells, the HIV infection is active; however, in rare human cells,
latent infection can occur at very early stage. These very small numbers of
latently infected cells called HIV reservoirs are located mainly in brain,
peripheral blood, and lymphoid tissue. In the reservoir cell sites antiviral
drugs penetration is often low. Moreover, even under antiretroviral therapy
(ART), about 30 to 50% of AIDS patients eventually develop HIV-associated
neurological disorders (HAND), which are cognitive, motor and/or behavioral
impairments caused by HIV infection in human brain. The ultimate cure for
HIV/AIDS would be the removal or disruption of integrated HIV provirus in
latently infected cells or the complete elimination of these latent cells.
However, gene therapy for HIV/AIDS has progressed very slowly.FIU inventors have developed composition
comprising a CRISPR-Cas protein or a CRISPR-Cas plasmid encoding a Cas9
protein, and one or more gRNAs that are effective for removing or disrupting an
HIV provirus genome integrated into the genome of a cell. These compositions
can be encapsulated in carriers, for example, liposomes, wherein the liposomes
carry on their surface one or more binding agents that bind specifically
molecules present on the surface of the target cells. The binding agents
present on the surface of liposomes can be an aptamer, an antibody or an
antigen binding fragment thereof, a ligand, etc., magnetic nanoparticles, and
liposomes. The compositions can also comprise magnetic nanoparticles for brain
targeting and blood brain barrier transmigration.Benefit
Can be specifically delivered to target cells without affecting the non-targeted cellsRepresents a new advanced therapeutic strategy to eliminate HIV provirus from HIV latent cellsMarket Application
Treatment, suppression, and eradication of latent HIV infection
Abstract
Despite significant advancements made in the development of
anti-retroviral (ARV) therapeutics, infections caused by HIV remain a serious
threat to human health. At the early stage of infection, HIV penetrates the
blood-brain-barrier (BBB) to enter the central nervous system (CNS), causing
neuroAIDS as well as the development of latent HIV reservoirs in the CNS.
Progression of HIV infection can gradually cause neuro-inflammation,
neurodegeneration, and other related diseases such as, for example,
HIV-encephalitis (HIVE). Additionally, neurological disorders associated with
HIV infection can become more severe with patients who consume substances of
abuse such as, for example, cocaine. Currently, enzyme-linked immunosorbent immunoassay (ELISA),
real time/quantitative polymerase chain reaction (RT/Q-PCR), and western blot
are the most commonly used analytical tools for monitoring HIV infection by
estimating p24 antigen, LTR level, and/or protein expression. Optical
assays-based surface plasmon resonance (SPR) system has also shown utility in
quantifying CD4+ cells for detecting the progression of HIV infections.
Unfortunately, these methods are expensive, time consuming (turnaround
detection time of 6-8 hours), and require technical expertise in
implementation.FIU inventors have developed an electrochemical method-based
on electrochemical impedance spectroscopy (EIS) for the rapid assessment of
HIV-infection on using substance of abuse and specific targeted therapeutic
drugs. The detection of HIV infection is accomplished by measuring the
electrochemical impedance of cells found in the CNS and/or the peripheral
nervous system (PNS), and determining changes in the electrophysiology of the
cells by comparing the measured electrochemical response of the cells with
pre-determined control measurements. Results confirmed that HIV-infection,
cocaine exposure, and therapeutic mechanism of drug affected electro-physiology
of cells which is detected as a function of charge transfer resistance (Rct).Benefit
Enables rapid assessment of HIV infection (e.g., less than 20 minutes)Suitable for point-of-care (POC) disease monitoring and treatment Allows timely treatment adjustmentMarket Application
Diagnosis and management of progression of HIV infections in the presence of a substance of abuse and/or therapeutic agent(s)
Abstract
Human immunodeficiency virus type
1 (HIV-1) remains one of the leading causes of death worldwide, principally in
developing countries. Although therapeutic agents exist for the treatment of
HIV-AIDS, drug-induced toxicities and pharmacokinetic limitations commonly
result in poor compliance and disease related complications such as, for
example, HIV-associated neurocognitive disorders (HAND). HAND is one of the
most common manifestations of HIV-1 pathogenesis that causes cognitive
impairment and other CNS-related disorders. For treating disorders such as
HAND, delivery of therapeutic agents to the CNS remains a major challenge,
primarily due to the ineffective transmigration of drugs through the
blood-brain barrier (BBB). In recent years, the advent of nanomedicine has
stimulated the development of innovative systems for drug delivery. However,
clinical success has been limited due to problems associated with
biocompatibility, sustainability, and cytotoxicity of the drugs.FIU inventors have developed
pharmaceutical compositions and methods for the delivery of Efavirenz to HIV
reservoir organs. The compositions comprise nanodiamond particles that are
small enough (less than 10 nm in diameter) to penetrate the tight junctions of
the BBB and subsequently migrate to selected treatment areas. The surface of
the ND particles can be electrostatically charged, facilitating the adsorption
of various therapeutic and/or diagnostic agents having positive or negative
charges. Optionally, the surface of the ND particles can be chemically modified
with functionalities such as, for example, carboxylic acid, lactone, ketone,
ether, hydroxyl, and/or amine. Furthermore, biological molecules such as, for
example, amino acids, proteins, cells, hormones, vitamins, DNAs, siRNAs,
antibodies, and RNAs, can be adsorbed or covalently attached to the ND
particles’ surfaces without altering their biological activities. Finally, the
increased drug-loading capacity attributed to ND particles’ large surface area
can lead to more sustained drug release profile and improve drug dosing
regimens.Benefit
Biocompatible and nontoxic to cells Can cross the blood-brain barrier Can adsorb large quantity of drug allowing sustained release of drug over long period of timeMarket Application
Targeted nanodrug delivery of anti-HIV drug to the HIV reservoir organs like the brain, lymphoid tissue, bone marrow, genital tract, and gut-associated lymphoid tissue Sustained release of drug Image guided drug deliveryPublications
Roy, U., Drozd, V., Durygin, A. et al. Characterization of
Nanodiamond-based anti-HIV drug Delivery to the Brain. Sci Rep 8, 1603 (2018).
https://doi.org/10.1038/s41598-017-16703-9
Abstract
Near infrared ray (NIR) based
technology is emerging as an important tool for studying different aspects of
biological systems as it offers several advantages over the ultraviolet and
visible spectral range, such as minimum absorption and scattering, and deeper
in vivo penetration. Further, when applied in conjunction with nanoparticles,
NIR irradiation can be employed for treating in vivo models of cancer or other
diseases. Unfortunately, due to the difficulty in minimizing or avoiding
damaging thermal effects on the brain cells, this combined technique has
largely been restricted to models of peripheral cancer therapy. In addition,
several instruments are required for simultaneously applying a photonic
irradiation source and optically evaluating its thermal effects on brain cells
and/or other tissues.FIU inventors have developed a
NIR exposure system for conducting photonic and optical treatments on
biological samples with additional functions including temperature monitoring
and real-time microscopic imaging. The system can also be combined with
nanoparticles (NPs) treatment to accomplish non-invasive, on-demand drug
targeting, brain cell specific gene delivery, and magnetized
photo-biomodulation for treating various CNS or peripheral disorder models.Benefit
Offers a single platform for simultaneous NIR phototargeting, and temperature and cell morphology measurements Provides a non-invasive tool for biological studies combining NPs and NIRMarket Application
Photonic and optical treatments of in-vitro brain cell cultures, in-vivo CNS and peripheral nervous system (PNS) tissue samples, as well as other body tissues Non-invasive, on-demand drug targeting, brain cell specific gene delivery, and magnetized photo-biomodulation for treating various CNS disorder models
Medical Devices
Abstract
Plant derived
compounds are known to exhibit a range of pharmaceutical and biological
activities. There are currently more than two dozen antiretroviral drugs used
for the treatment of HIV, and these drugs are divided into one of six classes
depending on how they attack the virus. The anti-retroviral drugs are usually
combined into three-drug cocktails called highly active antiretroviral therapy
or HAART. While the above-mentioned drugs can dramatically slow the disease's
progress if the patients strictly adhere to the treatment, they still cannot
effectively treat AIDS.FIU inventors
have developed methods to inhibit HIV-1 p24 antigen and therefore treat HIV/AIDS
with a composition comprising extract of Rubia cordifolia. The composition consists
of a hydro-ethanolic extract of Rubia cordifolia. The hydro-ethanolic extract is
obtained from the roots of a Rubia cordifolia plant and has demonstrated
anti-HIV activity. Benefit
· Significantly suppresses p24 antigen production indicating inhibition of HIV-1 · Significantly suppresses HIV-TLR gene expression in a dose dependent manner · Shows low toxicity to human cellsMarket Application
Inhibition of HIV-1 p24 antigen Treatment of HIV/AIDS
Abstract
HIV-1 still remains one of the
leading life-threatening diseases in the world. The introduction of Highly
Active Antiretroviral Therapy (HAART) has significantly reduced
HIV-infection-related morbidity and mortality. However, most antiretroviral
drugs have a short half-life and need to be in circulation constantly to
control the virus replication. As a result, it is believed that missing a
medication dose even once can provide an opportunity for viruses to replicate
such that a medication resistant HIV strain may develop. Being the largest
lymphoid organ, the gastrointestinal tract plays a key role in not only early
HIV infection in establishing viral reservoirs in gut-associated lymphoid
tissue (GALT) but also disease pathology. Many different treatment options have
been proposed to eradicate the virus from GALT; however, due to the complex
physiology involved, it is difficult to design drugs that are targeted toward
GALT.FIU inventors have developed
nanodrugs comprising an active agent, a poloxamer, and an antibody to
glycoprotein-2 (GP2) or antibody fragment to GP2 that targets microfold cells
(M-cells) and facilitates the uptake of the nanodrug by M-cells. M-cells are
specialized epithelial cells that are predominantly present in the GALT. Once
attached to the M-cells, the nanodrugs are transferred from intestine to GALT
via transcytosis mechanisms.Benefit
Survives stomach digestionReduce therapeutic dosage and associated side effectsDirectly act on the HIV-1 in GALTMarket Application
Targeted nanodrug delivery to the GALTTreatment of HIV-1 infectionPublications
Roy U, Ding H, Pilakka-Kanthikeel
S, et al. Preparation and characterization of anti-HIV nanodrug targeted to
microfold cell of gut-associated lymphoid tissue. Int J Nanomedicine.
2015;10:5819-5835. Published 2015 Sep 18. doi:10.2147/IJN.S68348
Abstract
With proper medications human
immunodeficiency virus (HIV) patients now live almost full lifespans; however, HAND
continues and its prevalence is increasing. This may be, in part, because HIV
infection remains in the brain. Anti-retroviral therapies (ARV)
have been shown to improve cognition and reduce the prevalence of
HIV-associated dementia; however, continued HIV infection and aging process
exacerbate the incidence of HAND. Since the beginning of the epidemic, drug
abuse and HIV infection have been inextricably linked, and neurocognitive
dysfunction is enhanced in HIV patients that are ingesting cocaine and other
drugs of abuse. Cocaine causes neuronal impairments as well as increases the incidence
and severity of HAND. Despite significant therapeutic advances made in the management
of HIV, effective treatments against HIV infection in the brain and the pathogenesis
of HAND remains a tremendous task.FIU inventors have developed compositions
and methods based on bifunctional plant molecule, Withaferine-A (WA), which can
eradicate HIV and remove neuronal amyloid beta (Aβ) protein. The formulations
comprise magnetic nanoparticles (MENPs) encapsulated with liposomes, and conjugated
to or mixed with therapeutic cargos comprising an HIV inhibitor (WA), an
inhibitor of beta-secretase 1 (BACE-1) activity or expression, and a cocaine
antagonist. Because of the high magnetic moments of the MENPs, the formulations
can deliver therapeutic cargos to desired body areas including across the blood
brain barrier (BBB) via the application of noninvasive external magnetic forces.
The components of the therapeutic cargos are then sequentially released from
liposomes via biodegradation or diffusion, and alternating current (a.c.)
trigger stimulation.Benefit
Allows for non-invasive delivery of therapeutic cargo to desired body areas including across the blood brain barrier Permits the sequential release of several therapeutic components from one single biocompatible nanoformulationMarket Application
Treatment or prevention of amyloid plaque mediated neuronal dysfunction in HIV infected patientsPublications
Tiwari S, Atluri VSR, Yndart Arias A, et al. Withaferin A
Suppresses Beta Amyloid in APP Expressing Cells: Studies for Tat and Cocaine
Associated Neurological Dysfunctions. Front Aging Neurosci. 2018;10:291.
Published 2018 Sep 27. doi:10.3389/fnagi.2018.00291
Abstract
Chronic
obstructive pulmonary disease (COPD) encompasses a spectrum of diseases
including chronic bronchitis (CB), reduced lung function, and emphysema and its
severity is linked to chronic mucus hypersecretion (CMH). CMH is a global
healthcare problem that is highly prevalent among people affected with allergic
asthma, including over 24.6 million in the USA with conservative estimates of
annual healthcare costs exceeding 81.9 billion dollars. Respiratory epithelial
cells of the conducting airways are a pivotal first line of defense against
airborne pathogens and allergens that orchestrate inflammatory responses and
mucociliary clearance. Unfortunately, the molecular mechanisms responsible for
epithelial hyperreactivity associated with allergic asthma, including the
regulation and function of lncRNAs in airway epithelium, are not completely
understood.FIU inventors
have identified a novel molecular species referred to as long noncoding RNAs (lncRNAs)
that are early innate sensors of cellular stress and are involved in the
regulation of airway inflammation and hyperreactive mucous response. AC011511.2
lncRNA comprises 3 exons and overlaps with intracellular adhesion molecule 1
(ICAM-1) on the antisense strand and regulates ICAM-1 expression and is
therefore, hereon referred to as LASI (LncRNA on Antisense
Strand to ICAM-1). Our researchers have designed and tested several
inhibitors that target the exon regions of LASI. One small interfering RNA targeting LASI successfully downregulated
its expression by more than 5-fold.Benefit
Decreases expression of an immunomodulatory lncRNA associated with hyperreactive response of airway epithelial cells Offers novel diagnosis and treatment options for airway diseasesMarket Application
Prevention, diagnosis, and treatment of pulmonary airway inflammation, asthma, chronic obstructive pulmonary diseases (COPD) and chronic mucus hypersecretion (CMH) pathogenesis and the target specificity of the genetic formulation will be helpful in possible combinatorial approaches with current pharmacotherapiesPublications
Devadoss, D., Daly, G., Manevski, M. et
al. A long noncoding RNA antisense to ICAM-1 is involved in allergic
asthma associated hyperreactive response of airway epithelial cells. Mucosal
Immunol (2020)
Abstract
Nanomedicine, which is based on administration of nanomaterials to prevent, diagnose, and/or treat diseases, has attracted attention for a few decades. Recent progress in nanotechnology facilitated biomedical applications of nanomaterials such as, drug carriers.Currently-available nanocarriers are capable of releasing therapeutic agents when subjected to external stimulation following targeted delivery to a treatment area of interest. However, many of these existing nanocarriers, in addition to requiring complexed formulation, are not applicable to a number of regions that are particularly sensitive to external stimuli such as, for example, heat. Furthermore, regions such as the brain possess cellular tight junctions that could limit the transmigration of nanocarriers to the targeted treatment area. As a result, there remains a need for nanocarriers that can be delivered in a targeted manner while accommodating various drug release mechanisms.FIU inventors have synthesized nanocarriers possessing novel features without
complexed formulations due to their magnetic and plasmonic properties. Their
features include enhanced targeting efficiency of therapeutic agents by
magnetic targeting, monitoring of the nanocarrier using multiple imaging
systems including magnetic resonance imaging (MRI), magnetic particle imaging
(MPI), X-ray computed tomography (CT), photoacoustic imaging, and raman
microscopy, and on demand release of therapeutic agents using various external
stimuli such as pH, temperature, alternating magnetic field, and near
infrared (NIR) light.Benefit
Enhanced targeting efficiency of therapeutic agents by magnetic targetingVisualization of therapeutic agent distributionControlled release of therapeutic agents by external stimuliMarket Application
Image-guided drug delivery with on demand-controlled release at desired time and site in the body.Personalized treatment of various diseasesPublications
Tomitaka A, Arami H, Raymond A, et al. Development of
magneto-plasmonic nanoparticles for multimodal image-guided therapy to the
brain. Nanoscale. 2017;9(2):764-773. doi:10.1039/c6nr07520g
Abstract
Zika virus, a mosquito-borne
pathogen, has been linked to occurrences of microcephaly when the virus is
passed from a pregnant woman to her fetus. Currently, enzyme-linked
immunosorbent assay (ELISA) and real time-polymerase chain reaction (RT-PCR)
are two major laboratory methods available for detecting Zika virus (ZIKV).
These methods can be used to detect the virus, for example, within 3-10 days following
the onset of symptoms. However, the ELISA test adopted for detecting Zika virus
has limitations due to cross reactivity of the antibodies with other species of
the Flavivirus genus such as, for example, dengue virus. In addition, ELISA is
cumbersome for healthcare workers to carry and utilize. Because these methods
are typically carried out in laboratories only, the turn-around time for
confirmed laboratory diagnostics results can take up to days, causing
significant delays in diagnosis and treatment. Furthermore, these test methods
are unable to detect Zika virus at low detection limits, which can result in
misidentification of the viral infection at an early stage.FIU inventors have developed
methods for the detection of zika virus at low level with micro-electrochemical
ZIKV immunosensors functionalized with Zika virus binding ligands such as
monoclonal Zika virus antibodies and Zika non-structural proteins. These
methods include contacting the immunosensing substrate with a biological
sample, applying a frequency to the sensing device, monitoring changes in
resistance response of the sensing device as Zika virus or Zika virus-infected
cells bind with their binding ligands; and finally, quantifying the amount of
ZIKV by comparing the measured resistance response with a pre-determined
calibration curve. These methods allow for a rapid (operation time around 40
minutes) and selective detection of ZIKV in wide concentration range with a low
detection limit (10 pM).Benefit
Suitable for use in clinical and field settings Enable early diagnosis of zika virus infection Allow for a sensitive, and selective detection of zika virus within 40 minutes Determine treatment effectivenessMarket Application
Diagnostic screening for zika virus infection at early stage Assessment of diseases progression and therapy efficacy