Breaking News
November 19, 2018 - New report calls for greater awareness and emphasis on scale and impact of atrial fibrillation
November 19, 2018 - In throes of turkey salmonella outbreak, don’t invite illness to your table
November 19, 2018 - UK health policies should be redesigned to become more accessible for men
November 19, 2018 - Short Interpregnancy Intervals Tied to Adverse Outcome Risk
November 19, 2018 - New mothers’ breastfeeding pain can affect infant health
November 19, 2018 - Stanford Medicine magazine reports on ways digital technology is transforming health care | News Center
November 19, 2018 - Human drugs alter cricket personality
November 19, 2018 - Insilico Medicine to introduce ‘Cure a disease in a year’ program at Biodata World Congress 2018
November 19, 2018 - Experts debate over whether gut or brain is more important in regulating appetite
November 19, 2018 - Playing on fear and fun, hospitals follow pharma in direct-to-consumer advertising
November 19, 2018 - Low-Carb Diets May Work By Boosting Calorie Burn
November 19, 2018 - Key molecule responsible for learning and memory discovered
November 19, 2018 - New blood test developed for early diagnosis of ovarian cancer
November 19, 2018 - Researchers identify molecule to fight myotubular myopathy
November 19, 2018 - New solution to stop spread of brain cancer
November 19, 2018 - Immune cells trigger OCD-like behaviour in multiple sclerosis, study finds
November 19, 2018 - Scientists equip new virus that kills carcinoma cells with protein
November 19, 2018 - Novel approach could provide painless, efficient alternative for treating eye diseases
November 19, 2018 - Protein in cell membranes of sperm plays key role in finding their way to eggs
November 19, 2018 - Parents who decline flu vaccination for their child may be exposed to limited information
November 19, 2018 - Mirati Presents Data From Ongoing Phase 2 Clinical Trial Of Mocetinostat In Combination With Durvalumab At The SITC 33rd Annual Meeting
November 19, 2018 - FDA warns of common diabetes meds’ link to dangerous genital infection
November 19, 2018 - New methods for preserving shoulder function, quality of life in breast cancer patients
November 19, 2018 - Surprising discovery about BH4 may rekindle interest in once-promising pathway
November 19, 2018 - Nabriva Therapeutics Completes Submission of New Drug Application to U.S. Food and Drug Administration for Intravenous Contepo to Treat Complicated Urinary Tract Infections
November 19, 2018 - Beating breast cancer only to die of opioid use – a sad Appalachian story
November 19, 2018 - Workplace bullying or violence linked to higher risk of cardiovascular problems
November 19, 2018 - Changes in Risk Indicators of MetS Severity Tied to T2DM Risk
November 19, 2018 - ‘Game-changing’ skin sensor could improve life for a million hydrocephalus patients
November 19, 2018 - Alcohol ads on social media sites with pro-drinking comments increase desire to drink
November 19, 2018 - Neural networks could replace marker genes in RNA sequencing
November 19, 2018 - Obese adolescents feel less food enjoyment than those with normal weight, study reveals
November 18, 2018 - Goodbye ‘Gluten-Free’? Celiac Disease Vaccine May Make It Possible
November 18, 2018 - Skin ages when the main cells in the dermis lose their identity and function
November 18, 2018 - Rainforest vine compound makes pancreatic cancer cells susceptible to nutrient starvation
November 18, 2018 - A new mechanism in the control of inflammation
November 18, 2018 - Age-related decline in abstract reasoning ability predicts depressive symptoms over time
November 18, 2018 - Scientists succeed in increasing stability, biocompatibility of light-transducing nanoparticles
November 18, 2018 - Sugar, a ‘sweet’ tool to understand brain injuries
November 18, 2018 - Pharmacist-Led Effort Cuts Inappropriate Rx in Older Adults
November 18, 2018 - Novel discovery could lead to new cancer, autoimmune disease therapy
November 18, 2018 - AHA and ADA launch new initiative to help people with type 2 diabetes reduce heart disease risk
November 18, 2018 - Balanced production of pro and anti-inflammatory cytokines at two years of age protects against malaria
November 18, 2018 - New pharmacological agent shows promise for prevention of heart rhythm disorders
November 18, 2018 - All That Social Media May Boost Loneliness, Not Banish It
November 18, 2018 - Scientists shine new light on link between obesity and cancer
November 18, 2018 - Risk factors for cardiovascular disease closely track with changes in diet patterns
November 18, 2018 - Biogen Scoops Sixth Prix Galien Award with UK Win for Life-Changing Rare Disease Medicine
November 18, 2018 - Detectable HIV-1 in treated human liver cells found to be inert
November 18, 2018 - Using light to control crucial step in embryonic development
November 18, 2018 - Unusual case of father-to-son HIV transmission reported
November 18, 2018 - FDA Approves Aemcolo (rifamycin) to Treat Travelers’ Diarrhea
November 18, 2018 - Poverty blamed on widening north-south gap in young adult deaths in England
November 18, 2018 - Progress in meningitis lags far behind other vaccine-preventable diseases, analysis shows
November 18, 2018 - Consensus Statement Issued on Management of Foot, Ankle Gout
November 18, 2018 - Fine particle air pollution is a public health emergency hiding in plain sight
November 18, 2018 - In-hospital mortality higher among patients with drug-resistant infections
November 17, 2018 - Research shines new, explanatory light on link between obesity and cancer
November 17, 2018 - FIND explores new diagnostic assays for confirmatory HCV diagnosis in community settings
November 17, 2018 - Tracking Preemies’ Head Size May Yield IQ Clues
November 17, 2018 - Scientists call for unified standards in 3-D genome and epigenetic data
November 17, 2018 - Lab Innovations 2018 has beaten all records by attracting 3,113 attendees
November 17, 2018 - New strategy to hinder emergence of antimicrobial-resistant pathogens
November 17, 2018 - Sexuality education before age 18 may reduce risk of sexual assault in college
November 17, 2018 - Reducing cellular proliferation could help deplete HIV reservoir and lead to a functional cure
November 17, 2018 - New model of FSHD could be useful to study effectiveness of experimental therapeutics
November 17, 2018 - FDA approves antibacterial drug to treat travelers’ diarrhea
November 17, 2018 - Lab Innovations 2018 confirmed as a major hit with visitors, exhibitors and speakers
November 17, 2018 - Largest parasitic worm genetic study hatches novel treatment possibilities
November 17, 2018 - UCLA biologists uncover how head injuries can lead to serious brain disorders
November 17, 2018 - Static and dynamic physical activities offer varying protection against heart disease
November 17, 2018 - Obesity significantly increases risk of Type 2 diabetes and coronary artery disease
November 17, 2018 - New method to analyze cell membrane complexes could revolutionize the way we study diseases
November 17, 2018 - Researchers show how proteins interact in hypoxic conditions to facilitate mitochondrial fission
November 17, 2018 - People with rare cancers can benefit from genomic profiling, shows research
November 17, 2018 - NIH awards over $1.8 million to husband-and-wife doctors to test new breast cancer approach
November 17, 2018 - Four-in-one antibody used to fight flu shows promise in mice
November 17, 2018 - New approach allows pathogens to be starved by blocking important enzymes
November 17, 2018 - Higher body mass index could cause depression even without health problems
November 17, 2018 - Protein which plays role in sensing cell damage serves as new target to treat pulmonary hypertension
Flare-responsive hydrogel developed to treat arthritis

Flare-responsive hydrogel developed to treat arthritis

image_pdfDownload PDFimage_print
Flare-responsive hydrogel developed to treat arthritis
A flare responsive drug delivery system titrates drug levels in response to the level of inflammation. Credit: Kai Slaughter

Arthritis flares – the unpredictable and often sudden worsening of arthritis symptoms—can be debilitating. These episodes can make the management of inflammatory arthritis, which includes rheumatoid arthritis and psoriatic arthritis, challenging for patients and physicians. But investigators at Brigham and Women’s Hospital have found that flares may also represent an important opportunity for improving treatment options for patients. In experiments carried out in the lab, BWH bioengineers have developed a hydrogel—a soft, flexible material that can be loaded with arthritis drugs and injected locally into an inflamed joint. Instead of delivering the drug continuously at a steady rate, the hydrogel is designed to respond to increased disease activity during flares, releasing the drug when symptoms worsen. The team’s laboratory-based findings are published this week in Nature Communications and investigators are working on next steps to bring their technology closer to the clinic.

“Arthritis represents a huge unmet clinical need,” said co-senior author Jeff Karp, PhD, a bioengineer and principal investigator at BWH. “Although new therapeutics have been developed, many have had systemic, toxic effects. We wanted to design a delivery system that could be efficient, deliver drugs locally and release drugs in response to inflammation.”

The newly created flare-responsive hydrogel is made from triglycerol monostearate (TG-18), a compound from the Food and Drug Administration’s list of “generally recognized as safe” compounds. TG-18 is a molecule capable of self-assembling, meaning that it can form a gel-like structure comprising fibers. This structure can be easily injected as a suspension In this study, the TG-18 hydrogel was loaded with triamcinolone acetonide (TA) used here as a model drug, but could potentially be loaded with many other kinds of anti-inflammatory compounds.

“The hydrogel is designed so that drug release is triggered by the activity of specific, arthritis-related enzymes that are increased during flares. To test the TG-18 hydrogel, we exposed the gel to several different kinds of environments mimicking conditions in arthritic joints,” said Nitin Joshi, co-first author on the work an Instructor of Medicine at BWH.

When the gel was incubated in synovial fluid from a healthy human joint, drug release was minimal, but when incubated in synovial fluid from a patient with rheumatoid arthritis, the drug was readily released from the hydrogel. Importantly, the drug supply was not exhausted in one spike of synovial fluid—instead, it could be released in response to multiple spikes over time. The team also tested hydrogel’s effects on cells from cartilage and joints, finding that it appeared to be safe.

The team further tested the clinical efficacy of the TG-18 hydrogel in a mouse model of inflammatory arthritis. They choose a model, the K/BxN serum transfer model, in which disease severity can be precisely controlled, which allowed them to test the hydrogel in animals with different degrees of arthritis severity. They found that when arthritis was more severe, the locally injected hydrogel degraded more rapidly corresponding to increased drug release. Swelling and severity of arthritis diminished in response to the drug-loaded hydrogel.

One of the advantages of the hydrogel is that it offers the promise of treating arthritis specifically in the joints where the disease is flaring, rather than delivering a drug throughout the body.

“Local therapy could be a viable treatment option for patients with only one or a few inflamed joints, said co-corresponding author Joerg Ermann, MD, a rheumatologist in the BWH Division of Rheumatology, Immunology and Allergy. “Moreover, if a patient is already on a systemic drug but is experiencing a flare in a limited number of joints, we could specifically treat these joints rather than switching systemic therapy or adding another systemic drug. Having this option would substantially increase our ability to successfully manage arthritis flares in the clinic.”

The team will continue testing the hydrogel in preclinical models to further validate it, and continue to advance toward human clinical trials. The technology has been licensed by Alivio Therapeutics, which is developing therapies to treat inflammatory disorders via targeted disease immunomodulation.


Explore further:
Gene expression study may help guide Arthritis care

More information:
Joshi N. et al. “Towards an Arthritis Flare-Responsive Drug Delivery System.” Nature Communications, DOI: 10.1038/s41467-018-03691-1

Journal reference:
Nature Communications

Provided by:
Brigham and Women’s Hospital

Tagged with:

About author

Related Articles