Preparation of liposomal brucine and its pharmaceutical/pharmacodynamic characterization.
OBJECTIVE
To prepare a novel transdermal preparation of liposomal brucine (LB) and investigate its pharmaceutical/pharmacodynamic characterization.


METHODS
LB was prepared by a modified ethanol-dripping method. Its drug encapsulation efficiency (EE), particle size, in vitro release, and skin permeation were studied. Furthermore, a safety evaluation and pharmacodynamic analysis of LB, including acute dermal toxicity, skin irritation, and analgesic and anti-inflammatory effects were investigated.


RESULTS
the EE of LB was 72% and the mean particle size of the liposomes was 55.4 nm. The in vitro release profile indicated that less than 68% of the encapsulated brucine was released in 10 h. A skin permeation study showed that compared with the free brucine, LB exhibited higher cumulative drug permeation through the skin and lower drug accumulation in skin tissue, indicative of an obvious promotion of skin permeation with liposomal encapsulation. The acute dermal LD50 of LB was greater than 100 mg/kg (brucine content) and skin irritation tests revealed that LB had no irritation to both integrity and broken skin. A pharmacodynamic evaluation of LB was performed by xylene-induced mouse ear edema test and acetic acid-induced writhing test at the dosage of 1.5, 3, and 6 mg/kg, respectively. The results showed that anti-inflammatory activities and analgesic effects of brucine encapsulated were significantly higher than that of the free brucine (P<0.01). Moreover, LB maintained a remarkably longer antiinflammatory and analgesic duration.


CONCLUSIONS
It can be proposed that LB prepared here could represent a safe, effective and promising transdermal formulation for analgesic and anti-inflammatory effects.
Qin
Xiang-qi
XQ
Key Laboratory for Ultrafine Materials of Ministry of Education, and Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China.
Yuan
Yuan
Y
Liu
Chang-sheng
CS
Wang
Qiu-yun
QY
Shen
Xi
X
Yang
Bai-can
BC
D000279:Administration, Cutaneous; D000700:Analgesics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D011817:Rabbits; D012867:Skin / Q000187:drug effects; D013331:Strychnine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D008081:Liposomes; C083806:brucine; D013331:Strychnine