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

Abstract

The aim of the present study was to develop a novel dosage form of multivesicular liposomes for oleanolic acid (OA) to overcome its poor solubility, prolong therapeutic drug levels in the blood, and enhance the antitumor effect on hepatocellular carcinoma. OA-encapsulated multivesicular liposomes (OA-MVLs) were prepared by a double-emulsion method, and the formulation was optimized by the central composite design. The morphology, particle size, and drug-loading efficiency of OA-MVLs were investigated. Furthermore, OA-MVLs were also characterized both in vitro and in vivo. The results showed that OA-MVLs were spherical particles with an average particle size of 11.57 μm and an encapsulation efficiency of 82.3%±0.61%. OA-MVLs exhibited a sustained-release pattern in vitro, which was fitted to Ritger–Peppas equation. OA-MVLs inhibited the growth of human HepG2 cells which was confirmed by the MTT assay and fluorescence microscopy detection. The in vivo release of OA from OA-MVLs exhibited a sustained manner, indicating a longer circulation time compared to OA solution. The in vivo toxicity study indicated that medium-dose OA-MVLs exerted no toxic effect on the hosts. Importantly, OA-MVLs suppressed the growth of murine H22 hepatoma and prolonged the survival of tumor-bearing mice. In conclusion, the poorly soluble OA could be encapsulated into MVLs to form a novel controlled-release drug delivery system. The present study may hold promise for OA-MVLs as a new dosage form for sustained-release drug delivery in cancer therapy.

Multivesicular Liposomes for the Sustained Release of Angiotensin I-Converting Enzyme (ACE) Inhibitory Peptides from Peanuts: Design, Characterization, and In Vitro Evaluation

“…Some dosage forms have been introduced, such as liposomes [11], nanoliposomes [12], nanoparticle suspension [13], oral microemulsion [14,15], and solid dispersions. However, these showed some shortcomings, such as poor long-term stability [16], small drug loading [17], and unobvious release effect. Multivesicular liposomes (MVLs) have received great attention due to their excellent stability and longer duration of release [16,18].…”

AMPK activation-dependent autophagy compromises oleanolic acid-induced cytotoxicity in human bladder cancer cells

“…Oleanolic acid (OA; 3β-hydroxyolean-12-en-28-oic acid), a pentacyclic triterpene compound, has been isolated from more than 1620 plant species and has also been biosynthesized from lupane [ 3 ]. OA possesses a wide range of pharmacological properties, such as hepato-protective, anti-diabetic, anti-viral and anti-cancer effects [ 4 ], and it has been shown to be effective for the treatment of a variety of human cancers, such as breast cancer [ 5 ], gallbladder cancer [ 6 ], hepatocellular carcinoma, among others [ 7 ]. Our previous study demonstrated that OA effectively inhibited cell viability and proliferation and promoted cell apoptosis and cell cycle arrest at G0/G1 phase via PI3K/AKT pathway in human prostate cancer cells [ 8 ].…”

NEP1-40-modified human serum albumin nanoparticles enhance the therapeutic effect of methylprednisolone against spinal cord injury

“…Cultures at ~ 70–80% confluence were washed three times with PBS and then incubated with 1 mL of the same concentrations of Alexa-NEP 1-40 -MP-NPs or Alexa-MP-NPs for 4 h at 37 °C. Cells were rinsed with PBS three times and fixed with paraformaldehyde (4%) for 15 min [41], then stained with 150 μL of DAPI (5 mg/mL) for 8 min. Subsequently, coverslips were sealed with glycerol and observed under a confocal laser scanning microscope, in which the emission of Alexa flour and FITC was set at 580 nm and 519 nm, respectively.…”