A nanoparticle that can stimulate growth of bone forming cells and deliver the drug used for osteoporosis straight to the affected area, has been developed.
About 9 million bone fractures occur each year due to osteoporosis, a progressive bone disease in which bone loses both its mass and density, thereby becoming weaker. Current treatment regimes involve restricting further bone damage, but not restoring previous strength. Zoledronic acid (ZOL) is the commonly used drug; it has successfully reduced risk of fracture in post-menopausal women. However, prolonged use of the drug can cause several adverse effects like unwanted bone changes.
A team of engineers and pharmacologists from IISc and Al-Ameen college of Pharmacy, Bangalore, has come up with a modified ZOL drug, which has proved to be effective in treatment of postmenopausal osteoporosis. What makes this novel mode of treatment even more special is the use of extremely small particles, called “nanoparticles”, for drug delivery.
The nanoparticles are made of synthetic hydroxyapatite (HA). HA is naturally present in our bodies: it makes up bone mineral and the matrix of teeth. It stimulates bone forming cells. The modified ZOL drug used in the study has a high affinity to bone, and prevents further bone loss.
“We have designed a new formulation, where the ZOL is first adsorbed on nanoparticles of hydroxyapatite and carried to osteoporotic bone by intravenous injection”, said lead author Deepak Kumar Khajuria. “We are able to demonstrate successfully that this formulation not only prevents further bone loss, but also stimulates bone growth”, he added.
The team used 12 week old female rats, whose ovaries were removed so that bone remodeling would not occur. Various doses of HA, ZOL and a combination of both were tested on the rats.
Three months after the treatment, the lumbar vertebra and femur (thigh bone) was tested for mechanical properties. Both showed better strength and structure after the combined treatment. A host of sensitive biochemical tests to predict whether new bone growth occurred were also carried out, all of which showed improvement with the combined treatment.
The binding of ZOL to synthetic HA maybe an effective way of delivering the two important minerals for bone structure – calcium and phosphate. While ZOL on one hand has been seen to kill the bone dissolving osteoclast cells, HA on the other has been shown to promote the bone forming osteoblast cells. The combination of both as shown in this study has taken best of the two properties and improved bone properties.
“The key aspect that was intriguing us during the early days of this study was that the carrier was also showing amplified benefit toward overall therapeutics when delivered along with the basic medicine like bisphosphonate”, said Prof. Rema Razdan.
“It took us several years to design a systematic scheme of investigation and method of correlation through various biochemical tests and mechanical testing of bone samples to establish the underlying complex process of nano-functionalized therapeutics and the efficacy of a single-dose”, said Prof Roy Mahapatra, who supervised the nanoparticle synthesis, characterization and biomechanical testing. This study shows a way forward for treatment or reversal of osteoporosis in humans, but further clinical trials are needed before reaching the medical shelf.
About the authors
Prof Roy Mahapatra is with the Department of Aerospace Engineering, Indian Institute of Science, Bangalore. The nanoparticles were formulated at IISc. Prof Rema Razdan is the Headof the Department of Pharmacology at the Al-Ameen College of Pharmacy, Bangalore. Deepak Kumar Khajuria is a joint student.
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The paper appeared in the European Journal of Pharmaceutical Scienceson 25th October 2014.