Friday, 20 Sep 2019

You are here

Dendrimer Nanocarrier Delivers IGF-1 to Degenerative Cartilage

Researchers from MIT have developed a novel treatment for osteoarthritis (OA) by using dendrimer-based nanocarriers to deliver insulin-like growth factor 1 (IGF-1) to chondrocytes within joint cartilage and in animal models have shown when these nanocarriers injected into rat knees in models of OA, they reduced cartilage degeneration.

Dendrimers are repetitively branched molecules containing highly symmetric, spherical compounds. In these experiments the nanocarriers allow the dendrimer–IGF-1 to penetrate and be retained by full-thickness bovine cartilage ex vivo. 

One of the challenges of delivering therapies (e.g., anabolic growth factors) to cartilage is that the tissue is that the chondrocytes reside deep within dense, anionic cartilage tissue. To overcome this biological barrier, they conjugated a IGF-1 (growth factor) to a cationic nanocarrier for targeted delivery to chondrocytes and retention within joint cartilage after direct intra-articular injection.

Amine terminal polyamidoamine (PAMAM) dendrimers were integrated with variable molar ratios of poly(ethylene glycol) (PEG) to control surface charge. Using variably PEGylated dendrimers, an optimal formulation showing 70% uptake into cartilage tissue and 100% cell viability was selected.

When conjugated to insulin-like growth factor 1 (IGF-1), the dendrimer penetrated bovine cartilage of human thickness within 2 days and enhanced therapeutic IGF-1 joint residence time in rat knees by 10-fold for up to 30 days.

Using a rat model of knee OA, a single injection of dendrimer–IGF-1 rescued cartilage and bone more effectively than free IGF-1. Dendrimer–IGF-1 reduced width of cartilage degeneration by 60% and volumetric osteophyte burden by 80% relative to untreated rats at 4 weeks after surgery.

These results suggest improve pharmacokinetics and efficacy of disease-modifying osteoarthritis drugs in the clinic.

This study shows that using that PEGylated PAMAM dendrimer nanocarriers with disease-modifying agents to target chondrocytes may be therapeutic in knee OA.

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

Add new comment

More Like This

Need for Pre-operative Hyperglycemia Testing Prior to Total Joint Replacement

JAMA reports on a large Medicare cohort study showing that amongst patients undergoing total joint replacement (TJR), preoperative HbA1c testing was performed in 26% to 43% of patients with diabetes and in only 5% of those without diabetes. Importantly research has shown that an elevated HbA1c level is associated with postoperative complications.

Weight Loss Cuts Hospital Stays for Obese TKA Patients

Morbidly obese patients who lost 20 lbs before total knee arthroplasty (TKA) cut their hospital stays by about 1 day, and were 76% less likely to have an extended hospital stay, research showed. 

High-Dose Vitamin D: No Help for Bone Health

Vitamin D might not be much help for strengthening bones among healthy adults without osteoporosis, Canadian researchers reported, even at doses far higher than recommended daily allowances. In a clinical trial assessing three levels of daily vitamin D supplementation -- 400 IU, 4,000 IU, and 10,000 IU -- radial volumetric bone mineral density was significantly lower among those (ages 55-70) taking higher doses for 3 years, according to Steven Boyd, PhD, of the University of Calgary in Canada, and colleagues.

Osteoporosis Tx: Good for Bones, but Not for Cutting Death Risk

Osteoporosis treatments were not linked with reduced overall mortality, according to a meta-analysis of placebo-controlled trial data.

Looking at data from 38 clinical trials, there was no significant association found between all drug-based osteoporosis treatments and overall mortality rate (risk ratio 0.98, 95% CI 0.91-1.05), reported Steven Cummings, MD, of the San Francisco Coordinating Center, and colleagues.

Bisphosphonate Use Associated with Reduced Mortality

The Journal of Bone and Mineral Research (JBMR) has published a report showing that a reduction in the rate of bone loss by nitrogen bisphosphonates was associated with a 40% lower mortality risk.

Accelerated bone loss has been shown to be an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown.