The Modification Of Non-Ionic Surfactant Brij78 And The Application Of Pa-Brij78

In this study the terminal hydroxyl group of a non-ionic surfactant Brij78 (polyoxyethylene (20) stearyl ether) was first modified to get three surfactants (Pa-Brij78, Dop-Brij78 and AA-Brij78). Pa-Brij78 was designed to target bone or HA-based bone graft substitute, Dop-Brij78 was designed to target titanium or titanium-based biomaterials and AA-Brij78 was designed for tumor targeting ligand. The structure of three surfactants was verified by 1H-NMR.Because Pa-Brij78 and hydroxyapatite (HA) has a strong affinity, it can be used as emulsifier to prepare drug-loaded nanoparticles which could combine hydroxyapatite. In this condition, using Pa-Brij78 as both a surfactant and an affinity ligand to HA, three different Pa surface functionalized nanoparticles were prepared, named as solid lipid nanoparticles (Pa-SNP), nanoemulsions (Pa-NEM) and PLGA nanoparticles (Pa-PNP). A model drug curcumin was successfully encapsulated in the three nanoparticles. The sizes of Pa-NEM and Pa-PNP were around 150 nm and the size of Pa-SNP was around 90 nm with polydispersity indexes (PDI) less than 0.20. Drug encapsulation efficiencies of the three nanoparticles were all greater than 85% and drug loading efficiencies of Pa-SNP and Pa-PNP were around 10% and that of Pa-NEM was around 30%, indicating the superior drug to carrier ratio of Pa-NEM. These three nanoparticles have good chemical and physical properties, with good drug loading capacity. The binding capacity of Pa-NPs and hydroxyapatite was studied by a series of in vitro experiments. The result showed the order of binding affinity of the nanoparticls to HA was Pa-PNP> Pa-NEM= Pa-SNP. After lyophilization, the sizes of the three nanoparticles were increased about 0.5-2.0 folds but their binding affinities to HA were almost the same as the fresh prepared nanoparticles. By optimizing the binding conditions of Pa-NPs and HA, HA/Pa-NPs complexes was successfully constructed. The drug loading and release capacity of Pa-NPs and HA/ Pa-NPs complex was test, using curcumin as a model drug. Although it suggests that Pa-NPs bind with HA by calcium on HA surface, the pre-formed HA/Pa-NPs composite can be stable in the presence of body fluid concentrations of calcium ions. The result showed HA/Pa-NPs composite have potential to be a stable drug-loaded bone graft substitute. And Pa-PNPs in the presence of body fluid concentrations of calcium ions can still maintain the ability to bind with hydroxyapatite, indicating Pa-PNPs have the potential for intravenous injection as a bone targeted drug delivery.In summary, this study designed and synthesized three surfactants (Pa-Brij78, Dop-Brij78 and AA-Brij78), studied the application of Pa-Brij78 on the nano synthesis, prepared a series of drug Pa-NPs, and constructed drug-loaded HA/ Pa-NPs composite. The composite can be used to prepare bone graft substitute. The Pa-PNPs could be a bone targeted drug delivery.