Stealth PEG-PHDCA niosomes: effects of chain length of PEG and particle size on niosomes surface properties, in vitro drug release, phagocytic uptake, in vivo pharmacokinetics and antitumor activity.

A series of novel niosomes with the amphiphilic copolymer of poly (methoxy-polyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) acted as surface modification materials were prepared and Hydroxycamptothecin (HCPT) was used as a model drug. This work concentrated on the effects of PEG chain length and particle sizes on the niosomes surface properties, in vitro drug release, phagocytic uptake, in vivo pharmacokinetics and antitumor activity. Within the range of PEG Mw from 2000 to 10000, the increasing zeta potential (from -16.08 to -5.25 mv) and thicker fixed aqueous layer (3.82 to 5.78 nm) would facilitate the niosomes' stealth effects, while the reduced PEG chain density (from 0.53 to 0.17 PEG/nm2) and the quickened speed of drug release would diminish the effects. As a result, the PEG5000-PHDCA niosomes had the least phagocytic uptake, the longest half-life of 11.46 h and the best tumor inhibition rate of 97.1%. In the groups different in particle size (PEG5000-PHDCA niosomes from 92.5 to 204.6 nm), the bigger particles could be uptaken by macrophages more quickly, regardless of the changes of other physicochemical parameters. Correspondingly, PEG5000-PHDCA niosomes with particle sizes of 92.5, 144.2, 204.6 nm could extend the half-life of HCPT to 11.46, 6.33, 4.46 h, respectively. At last, the tumor inhibition rate of PEG5000-PHDCA niosomes (92.5 nm) at a dose of 2 mg/kg was five times that of HCPT injection at 4 mg/kg. The stealth effects of the PEG-PHDCA niosomes and the enhanced stability of lactone form of HCPT were accountable for the powerful antitumor effects of niosomes. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association.