Studies On Poly (D, L-lactide) Nanoparticles Modified With Surfactants And Marked With CdSe Quantum Dots

Poly (D, L-lactide) (PLA) nanoparticles (NPs) have been extensively explored in medical area due to their great biocompatibility, good controlablity and high stability. Surfactants can increase the stability of NPs. Surfactants can also affect the drug release and in vivo distribution of NPs. It is important to study the effects of surfactants on PLA-NPs. In this work PLA-NPs modified with different surfactants were prepared. The effects of different surfactants on drug release in vitro and distribution in vivo were investigated using 5-aminofluorecein (5-AF) as model drug. Novel CdSe quantum dots (CdSe-QDs) encapsulated within PLA-NPs (CdSe-QDs-PLA-NPs) were prepared by nanoprecipitation method and the cytotoxicity of CdSe-QDs-PLA-NPs with surface modification was also studied.(1) PLA nanoparticles modified with different surfactants were prepared with the modified spontaneous emulsification and solvent diffusion method (modified-SESD method). The size of nanoparticles with poloxamer 188 was increased with the increase of the concentrations of PLA. The size of nanoparticles was increased with the hydrophobic properties of surfactants. The stability of PLA-NPs was increased with the increase of the surface charges. It was concluded that the hydrophilicity and the charge of the surfactants were the main factors on the size and the stability of PLA-NPs.(2) The effects of different solvents, pH values, surfactant solution and PLA nanoparticles on the fluorescence spectrum of 5-AF were investigated and the quantum yields of 5-AF were measured. The results showed that different solvents and pH values had different effects on the fluorescence intensity and spectrum. The high quantum yields indicated that it could be used in fluorescence analysis. Comparing to free 5-AF, those encapsulated in PLA-NPs had greater emission and excitation wavelength and fluorescence intensity.(3) The effects of different surfactants on drug release in vitro were investigated using 5-AF as model drug. PLA-NPs with different surfactants had different size and surface charge. BSA had good hydrophilicity with the smallest size of NPs while CTAB had very low hydrophilicity with the biggest size. PLA-NPs had low drug loading and high entrapment efficiency. PLA-NPs modified with poloxamer 188,BSA and SDS had similar drug release in vitro. The burst release was observed that more than 78% of the accumulative amount of 5-AF was observed within 4 h. However, PLA-NPs modified with CTAB had different release profile which was followed by a constant release until to more than 65% of the accumulative amount of 5-AF within 24h.(4) The effects of different surfactants on distribution in vivo were investigated using model drug except for CTAB, which had great cytotoxicity in vivo. Comparing to free 5-AF, the blood circulation half-life of 5-AF was significantly extended in PLA-NPs modified with surfactants. PLA-NPs with BSA showed significantly long-circulation characterization. Drug had different biodistribution because of the different affinities between drug or drug delivery system and organs. Comparing to free 5-AF, PLA-NPs with different surfactants showed different targeting tendency. PLA-NPs with SDS and BSA showed significantly liver targeting. The accumulative amount in liver of 5-AF-PLA-NPs with BSA kept a level of 15%. Therefore, BSA could be used to modify the drugs for liver targeting and sustained-release.(5) Novel CdSe-QDs-PLA-NPs modified with poloxamer 188 were prepared by nanoprecipitation method. The modified CdSe-QDs-PLA-NPs had good stability with low size and most of them were spherical with good dispersing. The emission wavelength of the modified CdSe-QDs-PLA-NPs was red-shift to 565 nm comparing to CdSe-QDs. The fluorescence of the modified CdSe-QDs-PLA-NPs was stable in aqueous solution for more than 30 d. The study of the distribution in vivo showed that the modified CdSe-QDs-PLA-NPs were distributed inhomogeneous in different organs at different time-points. The results indicated that the modified CdSe-QDs-PLA-NPs have much potential for biologic fluorescence imaging.(6) The cytotoxicity of CdSe-QDs-PLA-NPs with different surfactants was evaluated in HepG2 cell with MTT viability assay. The results showed that CdSe-QDs-PLA-NPs with different surfactans had different size, size distribution and charge. CdSe-QDs-PLA-NPs with poloxamer 188 showed slight cytotoxicity. CdSe-QDs-PLA-NPs with SDS didn't show any cytotoxicity with concentration of 10~50μg·mL-1. CdSe-QDs-PLA-NPs with CTAB showed significant cytotoxicity. The results indicated that CdSe-QDs-PLA-NPs modified with poloxamer 188 and SDS have low cytotoxicity and good potential for biologic fluorescence imaging.