Porous Hydroxyapatite Nanoparticle As A Controlled Release Carrier Of Skeletal-related Drugs

Hydroxyapatite (HAP, Ca10(PO4)6(OH)2), a bioceramic material, has been paid great attentions in the biomedical application for skeletal drug carrier and bone substitute due to its similar composition to natural bone, powerful adsorption ability, excellent biocompatibility and osteoconductibity. As a drug carrier, the effect of various morphologies and surface properties of HAP on the load ability of different pharmaceutical molecules is of great interest recently. However, few HAP drug carriers have been used in clinic because of their large size, poor injectability and stability, unreasonable release rate of drug, etc. In this work, vitamin C (VC, ascorbic acid) was used as a modifier to control the morphology of formed HAP particles and a model drug to be entrapped into the HAP particles in order to form the stable carrier.There are four sections in the research of porous hydroxyapatite nanoparticle as a controlled release carrier of skeletal-related drugs, including the preparation of VC loaded HAP nanoparticles; test and analysis of the obtained drug carrier's morphology, chemical composition, crystal characterization and so on, from the perspective of materials science; investigation of the carrier's drug release kinetics and sustained & controlled release behavior from the perspective of pharmaceutics; evaluation the bioactivity of the nanoparticles in vitro from the perspective of biology.Porous hydroxyapatite nanoparticles (PHNs) were repeatedly fabricated by chemical co-precipitation method with the assistant of the ultrasonic treatment in the present of vitamin C (VC), different drug content was successfully encapsulated into HAP nanoparticles. The morphology, Particle size distribution, Pore diameter distribution, materials phase, surface functional group, characterized and investigated by TEM, FE-SEM, nitrogen adsorption, XRD, FT-IR and ultraviolet spectrophotometer respectively. The results showed that VC encapsulated porous HAP nanoparticles were obtained by chemical co-precipitation method with the assistant of the ultrasonic treatment; these nanoparticles materials had wide size distributions and the average pore diameter below 15nm.Furthermore, VC storage capacities were analyzed; their release rates for VC were evaluated using the simulated body fluid (SBF) as the release medium. Both sustained release rate and controlled release rate under ultrasound treatment were fully understood. The results showed that the porous nanospheres possessed a sustained release for VC, which could be constantly released from the porous HAP for 1~2 months. The speed of drug release could be accelerated by increasing the power of ultrasonic treatment.In addition, the biologicl activity of the obtained porous materials was evaluated. Short term cell culture showed the materials hold the ability to induce ALP activity when VC was released from 2VC-PHNs. The results indicated the VC loaded HAP possessed the potential of stimulating collagen synthesis, osteocalcin accumulation and bone regeneration.This work successfully prepared poor crystal HAP nanoparticles with the ability of sustained release for bone-related drugs in the perspective of materials science, pharmaceuticals and biology. The porous HAP nanosphere was a promising candidate for skeletal drug delivery system, bone repair, dentistry and tumor.?...