Transmission electron microscope micrograph of calcium phosphate nanoparticles. Credit: ACerS
What may be a new and effective alternative to insulin injections is being reported in a paper (subscription required) to published in an online edition of ACerS’ International Journal of Applied Ceramic Technology. Researchers Willi Paul and Chandra Sharma, working in India, report favorable in vitro results from tests in which insulin was bound to nanoparticles of calcium phosphate.
Diabetes sufferers are always looking for an alternative to the standard multiple daily needle injections for delivery of their insulin. Some have sought relief from alternatives delivery–transport systems such as insulin pump systems and transdermal patches. An inhaled form was introduced in 2007 but pulled from the market by the maker after several problems were documented.
The holy grail for insulin therapy is is to find a satisfactory oral transport system. Among the benefits of the injection systems is that dosage and timing can be controlled, and the insulin isn’t altered by injection. Thus, any replacement system will have to meet these three minimum requirements.
One particularly difficult challenge for oral delivery methods to to have the insulin be attached to a carrier without fundamentally changing the insulin. Then, the system has to move the protein through the stomach intact so that it can later be absorbed in the gut. Several companies, including Oramed, are already working to bring one such product to market. The exact mechanisms these companies are using are uncertain and are closely held proprietary technologies, but it is assumed that these probably use some type of polymer system.
Now, however, it looks like Paul and Sharma may have devised a ceramic-based competitor (I recently wrote about another ceramic system that uses nanodiamonds to deliver insulin or genetic therapeutics). The method the duo uses is to first activate the phosphate group of the CaP. They then conjugate it with lauric acid and give it a chitosan spacer. Insulin is then loaded onto this substrate. Finally, the nanoparticles are given a coating of alginate that gives each particle a pH-dependent sustained release mechanism.
A battery of tests demonstrated that these ceramic particles had excellent biocompatibility with insulin:
Lauric acid conjugated CaP nanoparticles are highly compatible with insulin and the CaP–CH–LA system can deliver insulin in a sustained manner in the physiological pH of the intestine with no degradation or conformational changes of entrapped insulin. These nanoparticles are having a size distribution with majority of the particles <100 nm and have been demonstrated to be noncytotoxic. Because it is known that fatty acid complexation can improve uptake of particles across epithelium, the lauric acid conjugated CaP nanoparticles may be used as a carrier for delivering insulin orally.
While these results are exciting, much more work needs to be done, including in vivo tests. One issue that still needs to be documented is how quickly the CaP particles break down. Degradation within 24 hours would be ideal.
Paul and Sharma’s paper can be accessed via the ACT “Early View.”