Studies on pharmacokinetics and tissue distribution of oridonin nanosuspensions.
The purpose of the present study was to investigate the effects of particle size on the pharmacokinetics and tissue distribution of oridonin nanosuspensions after intravenous administration. Two oridonin nanosuspensions with markedly different size were prepared by high pressure homogenization method. The particle size of nanosuspension A is 103.3+/-1.5nm, while B is 897.2+/-14.2nm. Dissolution studies showed that complete dissolution could be obtained within 10min for nanosuspension A, however, nanosuspension B showed a slower dissolution, only 85.2% dissolved by 2h. The pharmacokinetics and tissue distribution of oridonin nanosuspensions A and B were studied after intravenous administration using New Zealand rabbits and Kunming mice as experimental animals, respectively. An Oridonin control solution was studied parallelly. The results showed that oridonin nanosuspension A exhibited pharmacokinetic and biodistribution properties similar to solution due to its rapid dissolution in blood circulation. Oridonin nanosuspension B, however, showed a high uptake in RES organs, meanwhile exhibited a markedly different pharmacokinetic property compared to nanosuspension A. These differences could be attributed to the different particle size of the two nanosuspensions considering their zeta potential had no significant difference. In conclusion, particle size showed obvious effects on pharmacokinetics and tissue distribution of nanosuspensions.
Gao
Lei
L
Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, China.
Zhang
Dianrui
D
Chen
Minghui
M
Duan
Cunxian
C
Dai
Wenting
W
Jia
Lejiao
L
Zhao
Wenfa
W
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D045786:Diterpenes, Kaurane / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004339:Drug Compounding; D005079:Excipients; D007275:Injections, Intravenous; D054709:Lecithins; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D020442:Poloxamer; D011817:Rabbits; D012995:Solubility; D013535:Suspensions; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D045786:Diterpenes, Kaurane; D005079:Excipients; D054709:Lecithins; D013535:Suspensions; C011959:oridonin; D020442:Poloxamer