论文部分内容阅读
Aim:To investigate the body distribution in mice of[~(14)C]-labeled polymethoxyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate(PEG-PHDCA)nanoparticles and in situ evading of phagocytic uptake by mouse peri-toneal macrophages.Methods:PEG-PHDCA copolymers were synthesized bycondensation of methoxypolyethylene glycol cyanoacetate with[~(14)C]-hexadecyl-cyanoacetate.[~(14)C]-nanoparticles were prepared using the nanoprecipitation/solvent diffusion method,while fluorescent nanoparticles were prepared by in-corporating rhodamine B.In situ phagocytic uptake was evaluated by flowcytometry.Body distribution in mice was evaluated by determining radioactivityin tissues using a scintillation method.Results:Phagocytic uptake by macroph-ages can be efficiently evaded by fluorescent PEG-PHDCA nanoparticles.After48 h,31% of the radioactivity of the stealth[~(14)C]-PEG-PHDCA nanoparticles afteriv injection was still found in blood,whereas non-stealth PHDCA nanoparticleswere cleaned up from the bloodstream in a short time.The distribution of stealthPEG-PHDCA nanoparticles and non-stealth PHDCA nanoparticals in mice waspoor in lung,kidney,and brain,and a little higher in hearts.Lymphatic accumula-tion was unusually high for both stealth and non-stealth nanoparticles,typical oflymphatic capture.The accumulation of stealth PEG-PHDCA nanoparticles in thespleen was 1.7 times as much as that of non-stealth PHDCA(P<0.01).But theaccumulation of stealth PEG-PHDCA nanoparticles in the liver was 0.8 times asmuch as that of non-stealth PHDCA(P<0.05).Conclusion:PEGylation leads tolong-circulation of nanoparticles in the bloodstream,and splenotropic accumula-tion opens up the potential for further development of spleen-targeted drug delivery.
Aim: To investigate the body distribution in mice of [~ (14) C] -labeled polymethoxyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate (PEG-PHDCA) nanoparticles and in situ evading of phagocytic uptake by mouse peri-toneal macrophages. Methods: PEG-PHDCA copolymers were synthesized by condensation of methoxypolyethylene glycol cyanoacetate with [~ (14) C] -hexadecyl-cyanoacetate. [~ (14) C] -nanoparticles were prepared using the nanoprecipitation / solvent diffusion method, while fluorescent nanoparticles were prepared by in -corporating rhodamine B. In situ phagocytic uptake was evaluated by flow cytometry. Body distribution in mice was evaluated by determining radioactivity in tissues using a scintillation method. Results: Phagocytic uptake by macroph-ages can be efficiently evaded by fluorescent PEG-PHDCA nanoparticles. After 48 h , 31% of the radioactivity of the stealth [~ (14) C] -PEG-PHDCA nanoparticles afteriv injection was still found in blood, as non-stealth PHDCA nanoparticleswere cleaned up from th e bloodstream in a short time. The distribution of stealth PEG-PHDCA nanoparticles and non-stealth PHDCA nanoparticals in mice waspoor in lung, kidney, and brain, and a little higher in hearts.Lymphhatic accumula tion was unusually high for both stealth and non -stealth nanoparticles, typical oflymphatic capture.The accumulation of stealth PEG-PHDCA nanoparticles in the complex was 1.7 times as much as that of non-stealth PHDCA (P <0.01) .But the accumulation of stealth PEG-PHDCA nanoparticles in the liver was 0.8 times asmuch as that of non-stealth PHDCA (P <0.05) .Conclusion: PEGylation leads tolong-on circulation nanoparticles in the bloodstream, and splenotropic accumula- tion opens up the potential for further development of spleen-targeted drug delivery.