Preparation, Safety, Pharmacokinetics, and Pharmacodynamics of Liposomes Containing Brucea javanica Oil

Abstract

Abstract. Brucea javanica oil-loaded liposomes (BJOL) were prepared through thin film hydration method and characterized by transmission electron microscope, dynamic light scattering, and differential scanning calorimetry. Acute toxicity of B. javanica oil (BJO) in liposomes was assessed by determining the number of deaths of Kunming mice over intravenous treatment for 2 weeks. The pharmacokinetic behavior of the main active component (oleic acid) was studied in SD rats. The pharmacodynamics of BJOL was investigated using MMC-7721 cell lines and mice with Lewis lung cancer. The commercial emulsion of BJO (BJOE) was used as a reference. The data showed that BJOL had an average diameter of 108.2 nm with a zeta potential of −57.0 mV, drug loading of 3.60%, and entrapment efficiency of 92.40%. The area under curve of BJO in liposomes and emulsions were 2.31 and 1.15 mg min/ml, respectively. Compared with BJOE, mean residence time and elimination half-time (t 1/2 ) increased 2.8-and 4.0-fold, respectively, and the clearance (CL) decreased 0.5-fold. In the acute toxicity test, the median lethal dose (LD 50 ) of BJOE was 7.35 g/kg. In contrast, all mice treated with liposomes survived even at the highest dosage (12.70 g/kg). The IC 50 value of BJOL group was one third of that of BJOE group (p<0.01), and a less weight loss was observed in the BJOL-treated animals (p<0.05). In conclusion, the present study suggests that BJOL significantly decreased toxicity of BJO and enhance the antitumor activity. Therefore, liposomes may be a potential effective delivery vehicle for this lipophilic antitumor drug.

Chemical Composition and Cytotoxic Activities of Petroleum Ether Fruit Extract of Fruits of <i>Brucea javanica</i> (Simarubaceae)

“…Brucea javanica oil extracted with petroleum ether from the fuits of B. javanica, is a complex mixture of fatty acids, which were reported to be cytotoxic active constituents [13]. The cytotoxic activity of petroleum ether fractions can be explained partly, by the high concentration of fatty acids and minor components such as sterides, pregnanones [18] and alkaloids.…”

“…Recent research has focused on the constituents of the ethyl acetate and n-butanol extracts of B. javanica. Brucea javanica oil (BJO) is a petroleum ether extract is mainly composed of fatty acids and fatty acid derivatives, which were extracted with petroleum ether from the fruits of B. javanica [13]. It has been used as anti-tumor agent to therapy hepatic, esophageal, rectal, pulmonic, renal, and prostatic carcinomas clinically [14].…”

Chemical components, pharmacological properties, and nanoparticulate delivery systems of Brucea javanica

“…The stability of the freeze-dried product was quite good and when compared with injection of the oil emulsion, the liposomes containing Brucea javanica oil had stronger antitumor activity with less toxicity. 38 Further, some researchers have reported the effect of these liposomes on human hepatoma cells, indicating that they inhibited proliferation of HepG2 cells and induced apoptosis, which suggests good potential for liposomal Brucea javanica in antineoplastic therapy. 39 …”

Preparation, characterization, and evaluation of antitumor effect of Brucea javanica oil cationic nanoemulsions

“…2 Oleic and linoleic acids in BJO are the main active ingredients for the antitumor activity (the total acid content in refined BJO is .95%), 3 and conjugated fatty acid can be metabolized to free fatty acids -oleic acid, producing effect in the body. 4,5 Many studies have shown that BJO has a variety of pharmacological activities, including anti-HIV (human immunodeficiency virus), antimalarial, antituberculosis, cytotoxic, and antitumor activities.…”

“…Related literatures have reported that the content of free fatty acid in fasting rats increases significantly (but fasting has different effect on free fatty acid in each rat), for example, the plasma concentration of oleic acid in rats was ~100 μg⋅mL -1 in the morning, 43,44 which is consistent with the results obtained in this experiment. Because there was a large amount of oleic acid in the fasting rats affecting the determination of oleic acid from the external source, we used the difference in value of oleic acid between the administration group and the blank group as the absorption of exogenous oleic acid 3 (as shown in Figure 6) and then calculated the related pharmacokinetic parameters (as listed in Table 2). Results indicated that compared with the BJO-E, AUC 0→∞ of BJO-CN significantly increased and that the relative bioavailability of BJO-CN to BJO-E was 1.6 times.…”