Body distribution and in situ evading of phagocytic uptake by macrophages of long-circulating poly (ethylene glycol) cyanoacrylate-co-n-hexadecyl cyanoacrylate nanoparticles.
OBJECTIVE
To investigate the body distribution in mice of [14C]-labeled poly methoxyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate (PEG-PHDCA) nanoparticles and in situ evading of phagocytic uptake by mouse peritoneal macrophages.


METHODS
PEG-PHDCA copolymers were synthesized by condensation of methoxypolyethylene glycol cyanoacetate with [14C]-hexadecyl-cyanoacetate. [14C]-nanoparticles were prepared using the nanoprecipitation/solvent diffusion method, while fluorescent nanoparticles were prepared by incorporating 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 macrophages can be efficiently evaded by fluorescent PEG-PHDCA nanoparticles. After 48 h, 31% of the radioactivity of the stealth [14C]-PEG-PHDCA nanoparticles after iv injection was still found in blood, whereas non-stealth PHDCA nanoparticles were cleaned up from the bloodstream in a short time. The distribution of stealth PEG-PHDCA nanoparticles and non-stealth PHDCA nanoparticals in mice was poor in lung, kidney, and brain, and a little higher in hearts. Lymphatic accumulation was unusually high for both stealth and non-stealth nanoparticles, typical of lymphatic capture. The accumulation of stealth PEG-PHDCA nanoparticles in the spleen 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 as much as that of non-stealth PHDCA (P< 0.05).


CONCLUSIONS
PEGylation leads to long-circulation of nanoparticles in the bloodstream, and splenotropic accumulation opens up the potential for further development of spleen-targeted drug delivery.
Huang
Min
M
School of Pharmacy, Fudan University, Shanghai 200032, China.
Wu
Wei
W
Qian
Jun
J
Wan
Dan-Jing
DJ
Wei
Xiu-Li
XL
Zhu
Jian-Hua
JH
D000818:Animals; D003487:Cyanoacrylates / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D010587:Phagocytosis; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D013154:Spleen / Q000378:metabolism*; D014018:Tissue Distribution
D003487:Cyanoacrylates; D004337:Drug Carriers; C504655:poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate); D011092:Polyethylene Glycols