Stability and in vivo evaluation of pullulan acetate as a drug nanocarrier.
To develop pullulan acetate nanoparticles (PANs) as a drug nanocarrier, pullulan acetate (PA) was synthesized and characterized. Its acetylation degree determined by the proton nuclear magnetic resonance ((1)H NMR) was 2.6. PANs were prepared by the solvent diffusion method and characterized by transmission electron microscope (TEM), size distribution, and zeta potential techniques. PANs had nearly spherical shape with a size range of 200-450 nm and low zeta potentials both in distilled water and in 10% FBS. The storage stability of PANs was observed in distilled water. PANs were stored for at least 2 months with no significant size and zeta potential changes. The safety of PANs was studied through single dose toxicity test in mice, and the result showed that PANs were well tolerated at the dose of 200 mg/kg in mice. Epirubicin-loaded PANs (PA/EPI) were also prepared and characterized in this study. Moreover, the in vivo pharmacokinetics of PA/EPI was investigated. Compared with the free EPI group, the PA/EPI group exhibited higher plasma drug concentration, longer half-life time (t(1/2)) and the larger area under the curve (AUC). All results suggested that PANs were stable, safe, and showed a promising potential on improving the bioavailability of the loaded drug of the encapsulated drug.
Tang
Hong-Bo
HB
Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Peking Union Medical College, The Key Laboratory of Biomedical Material of Tianjin, Tianjin 300192, PR China.
Li
Lei
L
Chen
Han
H
Zhou
Zhi-Min
ZM
Chen
Hong-Li
HL
Li
Xue-Min
XM
Liu
Ling-Rong
LR
Wang
Yin-Song
YS
Zhang
Qi-Qing
QQ
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D004355:Drug Stability; D015251:Epirubicin / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D005936:Glucans / Q000737:chemistry* / Q000633:toxicity; D006207:Half-Life; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005936:Glucans; D015251:Epirubicin; C009109:pullulan