Preparation, characterization, and in vivo pharmacokinetics of nanostructured lipid carriers loaded with oleanolic acid and gentiopicrin

Abstract

Background:The purpose of this work was to develop nanostructured lipid carriers (NLCs) loaded simultaneously with oleanolic acid and gentiopicrin. Methods: An aqueous dispersion of NLCs was prepared successfully using a film-ultrasonic method, with glycerin monostearate as the solid lipid and oleic acid as the liquid lipid. Poloxamer 188 was used as the surfactant. A central composite design was used to optimize the technologic parameters. The characteristics of the NLCs were then investigated. Results: The encapsulation efficiency was 48.34% ± 2.76%, drug loading was 8.06% ± 0.42%, particle size was 111.0 ± 1.56 nm, polydispersity index was 0.287 ± 0.01, and zeta potential was −23.8 ± 0.36 mV for the optimized NLCs. The other physicochemical properties were characterized by transmission electron microscopy and differential scanning calorimetry. Drug release followed first-order kinetics and release studies confirmed that oleanolic acid and gentiopicrin fitted a sustained-release model. Compared with NLCs loaded with oleanolic acid or gentiopicrin alone, NLCs loaded with both oleanolic acid and gentiopicrin produced drug concentrations which persisted for a significantly longer time in plasma, with a linear decrement following second-order kinetics. Aspartate and alanine aminotransferase levels were significantly lower on exposure to NLCs loaded with both oleanolic acid and gentiopicrin than in negative controls. Conclusion:The results of this study confirm that oleanolic acid and gentiopicrin can be loaded simultaneously into NLCs. Compared with oleanolic acid and gentiopicrin loaded alone, sustained release and protective effects against hepatic injury were observed using NLCs loaded with both oleanolic acid and gentiopicrin.

Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo

“…The dose selection was based on previous reports from the literature. 16,28,29 Our results showed that OA-MVLs were more effective for inhibiting tumor growth ( Figure 9A) and prolonging survival times ( Figure 9B) in a dose-dependent manner, compared to the saline and OA solution. The enhanced antitumor activity of OA-MVLs may be due to the slow-release effect which was confirmed by both release profile in vitro and plasma pharmacokinetic studies in vivo.…”

“…Drug administration and blood sample collection Two groups of five rats each were treated with OA solution or OA-MVLs at a single dose of 10 mg/kg via subcutaneous (sc) injection; 16 the OA solution was prepared by dissolving OA in polyethylene glycol 400 (0.2%) and further diluting with saline for injection. Blood samples were collected from the ophthalmic veins after administration.…”

“…16,28,29 All the animals were given an ip injection of 2 mL of different formulations mentioned, on every other day for 30 days, and their body weight was weighed at every other week. Moreover, all the animals were observed once daily for the signs of toxicities and twice daily for mortality.…”

“…The tumor-bearing mice were divided randomly into five groups (n=10) as follows: I, saline as control; II, OA solution; III, low-dose OA-MVLs, 25 mg/kg; IV, mediumdose OA-MVLs, 50 mg/kg; and V, high-dose OA-MVLs, 100 mg/kg. 16,28,29 On day 5 post-inoculation of cancer cells when the tumors reached a volume of 70-100 mm 3 , the treatments were initiated by ip injection with 500 μL of the solution mentioned. Meanwhile, every group was randomly divided into part A and part B with five mice each.…”

“…Some dosage forms of OA have been introduced such as liposomes, 15 nanoliposomes, 16 nanoparticle suspension, 17 oral microemulsion, 18 and solid dispersions, 19 but they showed some shortcomings, such as poor long-term stability, small drug loading, and unobvious release effect. Multivesicular liposomes (MVLs) have received great attention due to their excellent stability and longer duration of release.…”