Characterization of Calcium Phosphosilicate (Hydrate) Nanoparticles: Novel Organic-Inorganic Composite Nanomaterial for Drug and Diagnostic Delivery

Abstract

Calcium phosphosilicate nanoparticles (CPSNPs) were developed to deliver drugs and imaging agent in the treatment of human cancer. The material is an amorphous calcium phosphate [nominal composition Ca1.67(PO4) (1-x) SiO3(x)], where 0<x<0.1. The CPSNPs are precipitated at 25 °C within a reverse micelle system that permits the formation of nanoparticles (~15 to 35nm diameter) intentionally composed of the amorphous calcium phosphate phase (Figure 1) [1]. One of the goals for the CPSNPs is to encapsulate small, and awkwardly shaped drugs including the chemotherapeutics, 5-fuoro-uracil and gemcitabine, and imaging agents such as indocyanine green and Rhodamine WT. Thus, the amorphous phase is preferred because this phase can accommodate the encapsulation of the drugs in the amorphous material matrix far better than the corresponding crystalline phases. During development, we discovered that small substitutions of meta-silicate ion (SiO3 2-) for the phosphate (PO4 3-) yield an amorphous calcium phosphate that is more stable than pure, amorphous calcium phosphate. During the development, obtaining TEM images to guide the process was found to be very difficult. The CPSNPs were difficult to obtain images with our standard analytical TEM approaches. Through much trial and error, it was established that electron beam damage was compromising the ability to obtain TEM images. Therefore, we moved from the materials side of our TEM facilities at Penn State over to the life sciences TEM facilities designed in part to image delicate biological samples.