PEGylated calcium phosphate nano-carriers.
Han, Jamie YuLing.
Date of Issue2011
School of Materials Science and Engineering
Calcium phosphate (CaP) nanoparticles (NPs) grafted with methoxy poly(ethylene) glycol (mPEG) were studied as carriers in this thesis. The objectives of this thesis are to (1) develop a superior technique in synthesizing CaP NPs to study and compare the effect of protein amount and type on loading efficiency with conventional co-precipitation (co-ppt) method and (2) develop two procedures to chemically graft mPEG onto CaP NPs and determine which is the better technique. Also, the effect of mPEG chain length, in the prevention of protein adsorption was studied to establish the optimal chain length. It was shown that protein-loaded CaP synthesized by the IM technique is more homogenous in morphology and more importantly, has considerably higher loading efficiency as compared to co-ppt. In addition, protein were found to be released continuously for IM samples while for co-ppt samples, a burst release with little or no subsequent release was observed, thus concluding that IM was a superior technique in loading proteins to CaP NPs. Subsequently, CaP NPs were PEGylated via Direct and Linker techniques. The former was found to be better in terms of higher surface density and has relatively lower cumulative percentage mass of protein adsorbed to it in the protein binding tests. It was also found that surface density of mPEG of chain length 2000 grafted onto CaP is 67 % higher as compared to mPEG of chain length 5000, which resulted in lower adsorption of specific and non-specific protein. Cellular uptake studies with mouse leukemic monocyte macrophage cell line RAW 264.7 showed that CaP-isc-mPEG2000 was able to delay protein from adsorbing for up to 12 h while CaP-isc-mPEG5000 was able to do so for only up to 3 h.