Ammonium sulfate gradient loading of brucine into liposomes: effect of phospholipid composition on entrapment efficiency and physicochemical properties in vitro.
BACKGROUND
Brucine, the major active alkaloid constituent extracted from traditional Chinese herbal medicine Nux vomica, had been found to possess remarkable antitumor, analgesic, and anti-inflammatory activities. In this study, we attempted to encapsulate brucine into liposomes to improve its therapeutic effects. The entrapment efficiency (EE) and the stability of liposomes are two key factors associated with the therapeutic effects of liposomal drugs. We developed a novel liposome-based brucine formulation that was composed of soybean phosphatidylcholine (SPC) and hydrogenated soybean phosphatidylcholine (HSPC).


METHODS
The liposomes with different phospholipid composition were characterized for their EE, vesicle size, drug release profile, and leakage in vitro.


RESULTS
The molar ratio of HSPC/SPC = 1:9 was determined as the optimum ratio. Compared with conventional liposomes composed of only SPC or HSPC, EE of the brucine-loaded novel liposomes was increased markedly, especially at high drug/lipid molar ratios. The results of drug release showed that the novel liposomes were more stable than the conventional SPC liposomes in the presence of fetal calf serum. In addition, the results of the leakage experiments revealed that the novel liposomes also had better stability in phosphate buffer solution (PBS) with respect to drug retention. Although the conventional HSPC liposomes is more stable than the novel liposomes, the novel liposomes composed of 10% HSPC and 90% SPC may still have promising application potential because HSPC is much more expensive than SPC.


CONCLUSIONS
Taken together, efficient encapsulation of brucine into the novel liposomes, their improved stability, and the price of phospholipids indicate that the novel liposomes may act as promising carriers for active alkaloids such as brucine.
Chen
Jun
J
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, PR China.
Lin
Aihua
A
Chen
Zhipeng
Z
Wang
Wei
W
Zhang
Ting
T
Cai
Hao
H
Cai
Baochang
B
D000645:Ammonium Sulfate / Q000737:chemistry*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000633:toxicity; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000633:toxicity; D055598:Chemical Phenomena; D004337:Drug Carriers / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry* / Q000633:toxicity; D006865:Hydrogenation; D007928:Lethal Dose 50; D008081:Liposomes; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry / Q000191:economics; D010743:Phospholipids / Q000737:chemistry* / Q000191:economics; D012639:Seeds / Q000737:chemistry; D044967:Serum / Q000737:chemistry; D013025:Glycine max / Q000737:chemistry; D013331:Strychnine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000633:toxicity
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D010713:Phosphatidylcholines; D010743:Phospholipids; C083806:brucine; D013331:Strychnine; D000645:Ammonium Sulfate