Friday, 18 Oct 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

High Dose Statins Increase Odds of Osteoporosis

It is unknown if inhibiting cholesterol synthesis (with statins) might influence sex-hormone production and therefore, the risk of osteoporosis. A new study shows that, in statin-treated individuals, the development of osteoporosis is statin dose-dependent.

Sprifermin Benefits Cartilage Loss but not Symptoms in Knee Osteoarthritis

Intra-articular sprifermin given to patients with symptomatic and radiographic knee osteoarthritis has been shown to significantly improve total femorotibial joint cartilage thickness after 2 years, but without significant clinical benefits. Which begs the question, why is there a disconnect between radiographic disease modification (cartilage thickness) and symptomatic improvement?

Bisphosphonates and the Risk of Osteonecrosis of the Jaw

Even though oral bisphosphonates are widely used, there is an inordinate concern over the risk of osteonecrosis of the jaw (ONJ). A new UK study suggests that the risk of ONJ is elevated six fold by the use of biphosphonates.

ASBMR Recommendations on Secondary Fracture Prevention

The American Society for Bone and Mineral Research has developed multistakeholder consensus clinical recommendations for the prevention of secondary fractures for those aged 65 years and older after an initial hip or vertebral fracture.

Overall they have promoted 13 recommendations (7 primary and 6 secondary) strongly supported medical evidence.

Highlights include recommendations for:

Similar Outcomes for Hip Arthroplasty or Hemiarthroplasty in Hip Fracture

The NEJM reports on a randomized comparison of hemiarthroplasty and total hip arthroplasty in displaced femoral neck fractures and shows no difference in function and quality of life over 24 months.