Application of calcium phosphate as a controlled-release device

Abstract

Calcium phosphate (CaP)-based compounds are biocompatible and have been accepted as promising candidates for novel drug-releasing devices. CaP is biodegradable and can be utilized as a durable drug release reservoir. We developed an injectable self-setting apatite cement. When a plasmid DNA complex containing CaP was injected into tumor-bearing mice, it solidified in the body and slowly released the DNA complex, inducing durable gene expression and high therapeutic effect on solid tumors. Encapsulation of a drug by CaP acts as a protective capsule for the unstable contents and improves biocompatibility. CaP nanocapsules encapsulating a plasmid DNA complex or drug-involved micelle were prepared, and they showed high stability against enzyme and protein degradation. CaP also showed high potential as a durable acid pH buffer. Aqueous alginate solution was found to form a soft gel in the body and was investigated as a drug-releasing device. However, degradation of the alginate gel is sometimes too rapid in an acidic environment such as the area around osteoporotic bones. We found that amorphous CaP powder added to the alginate gel could control the dissociation rate, buffering the pH inside the gel. Alginate gel including CaP powder and a drug for osteoporosis allowed sustained release of the drug under acidic conditions, and a good therapeutic effect was achieved in osteoporosis model rats. CaP could thus be a valuable material for drug-delivery systems as a slow-releasing drug reservoir, a protective coating, or a pH buffer.