drug delivery

A recent review by a group in Switzerland covers current and future perspectives for the treatment of osteoarthritis, and the use of cutting-edge drug delivery systems to improve the effectiveness of treatments.

Osteoarthritis is the most common form of arthritis. It affects the joints in the knees, hips, fingers and lower spine region. Those who suffer from this degenerative condition know all too well the pain, stiffness and inflammation that comes along with joint deterioration.

Many different factors play into the likelihood of developing osteoarthritis. Some of these factors include age, gender, exercise, genetics, diet and previous injuries or trauma. The World Health Organization (WHO) estimates that about 18% of women over 60 years old have osteoarthritis, while almost 10% of men over 60 show symptoms of the disease.

Osteoarthritis is a difficult disease to treat effectively. Oral treatments, like taking pills, often do not provide the amount of drug that is necessary and they often do not treat the exact region that is affected. Because the symptoms of osteoarthritis are usually only present in one or two joints per patient, researchers have recently considered alternative options for drug delivery.

The method with the most potential of treating osteoarthritis effectively is called intraarterial administration (IA). This method involves a drug or other treatment being injected directly into the local joint area.

A recently published article in the journal Drug Delivery Today details the current state of affairs and future considerations in osteoarthritis treatment. The authors, from the School of Pharmaceutical Sciences at the University of Geneva, provide a detailed description of the disease hallmarks of osteoarthritis, the classification of current drugs, and the drug delivery systems that are being considered and tested to maximize the efficiency of IA. The following sections provide a summary of the most important points of the review.

Types of Osteoarthritis Drugs

The progression of osteoarthritis is not very well understood. This is one part of the problem in designing or finding drugs to treat the disease.

Joints are made up of many different kinds of tissues and cells, and there are likely many molecular pathways involved in osteoarthritis that researchers have not characterized. Because of this, much of the research into drug development has focused on finding molecules that could produce fast results for patients, targeting specific tissues based on our current knowledge. Broadly, osteoarthritis drugs can be classified into two groups:

  • Pain-relieving drugs: These don’t address any specific mechanism in the disease but help provide relief to patients.
  • Disease-modifying osteoarthritis drugs (DMOADs): These are designed to bind to targets that change some disease characteristics or the course of the disease.

Drug Delivery Systems for Intraarterial Injections

While research into new drugs for osteoarthritis is ongoing, an equally important area of study focuses on designing delivery systems to get the drugs where they need to go—and keep them there.

Free drugs injected into the joint space get rapidly cleared away by the body’s metabolism. This means that the bioavailability – the amount of drug actually present where it needs to be – is very low. In response to this, researchers have developed a series of innovations to efficiently deposit pharmaceutical agents for treatment and to promote the slow release of these drugs over time.

Hydrogels

Hydrogels are materials made of natural or synthetic polymers (long chains of molecules) that become swollen with water. Hydrogels can maintain a distinct 3D structure and can be loaded with a dose of drugs. Researchers have performed several clinical trials with hydrogels but they have shown only small improvements in keeping drugs in the joint areas.

Liposomes

Liposomes are synthetic preparations of molecules that can mimic some properties of cell membranes and carry a variety of drugs. Liposomes provide a slow and controlled release of the drug, which has been verified in clinical trials. However, they sometimes cannot maintain their structure within the high-pressure environment in and around the joints.

Nanoparticles

Nanoparticles are small, solid entities composed of biodegradable material that can be loaded up with drugs. Different sizes have shown differences in their penetration, retention and release properties. Nanoparticles are particularly effective for delivering drugs to a known and specific target in the joint space.

Microparticles

Microparticles are like nanoparticles, but microparticles are about 10 times bigger. Certain sizes of microparticles have shown the most favourable results for the slow release of drugs, displaying retention of up to six weeks. Even though they are larger in size, they cannot accommodate a high dose of a loaded drug. Because of this, microparticles must often be administered over multiple injections.

Intraarterial injections: A promising approach

Using intraarterial injections for treating osteoarthritis looks like a promising approach for treatment in the future. While only microparticles have demonstrated experimental effectiveness in retention and release of drugs in the joint space, the other drug delivery methods could prove useful for targeting specific tissues. Overall, there appears to be a variety of options for patients that may become clinically available in the near future.

Written by Adriano Vissa, PhD

Reference: Maudens P, Olivier J, Allemann E. Recent advances in intra-articular drug delivery systems for osteoarthritis therapy. Drug Discovery Today (2018). https://doi.org/10.1016/j.drudis.2018.05.023

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