Stealth PEG-PHDCA niosomes: effects of chain length of PEG on niosomes in vitro complement consumption and phagocytic uptake.
OBJECTIVE
Poly (methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate) (PEG-PHDCA) and PHDCA niosomes were prepared and the influence of the PEG chain length on the niosomes physicochemical characteristics, complement consumption and phagocytic uptake were studied.


METHODS
The physicochemical parameters of PEG-PHDCA niosomes were characterized in terms of particle size, zeta aqueous layer thickness. The relationship between physicochemical characteristics and in vitro complement consumption and phagocytic uptake was further illustrated.


RESULTS
Experimental results showed that PEG10,000-PHDCA had most loose structure and least PEG surface density among three groups. Configuration simulation through fixed aqueous layer thickness confirmed that PEG folding and less flexibility of the PEG chains of PEG10,000-PHDCA niosomes were accountable for its poor stealth effects. Compared with PEG2,000-PHDCA, PEG5,000-PHDCA showed a thicker fixed aqueous layer (FALT) of 4.20 nm, less negative zeta potential of -10.03 mV, and enhanced PEG surface density of 0.49 PEG x nm(-2), leading to the best effects of reduction of complement consumption and phagocytic uptake.


CONCLUSIONS
Excessive chain length of PEG was not necessary for stealth effects of PEG-PHDCA niosomes. PEG5,000-PHDCA niosomes had best effects on evading complement consumption and subsequent phagocytic uptake.
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China. sb750317@163.net
Bin
B
Shi
Chao
C
Fang
Mei-xian
MX
You
Ming-huang
MH
Hong
Yuan-ying
YY
Pei
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003165:Complement System Proteins / Q000378:metabolism*; D003487:Cyanoacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D004337:Drug Carriers; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D010316:Particle Size; D010587:Phagocytosis; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D013499:Surface Properties
D000972:Antineoplastic Agents, Phytogenic; D003487:Cyanoacrylates; D004337:Drug Carriers; C504655:poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate); D011092:Polyethylene Glycols; D003165:Complement System Proteins; C028098:10-hydroxycamptothecin; D002166:Camptothecin