Preparation of honokiol nanoparticles by liquid antisolvent precipitation technique, characterization, pharmacokinetics, and evaluation of inhibitory effect on HepG2 cells

Abstract

BackgroundHonokiol is a bioactive lignanoid and has been utilized in traditional Chinese medicine for a long time. It exhibits several pharmacological properties, such as anticancer effects, anti-inflammatory effects, and antianxiety effects. However, the poor aqueous solubility of honokiol has impeded clinical applications.Materials and methodsIn the present study, we adopted the liquid antisolvent precipitation (LAP) technique to prepare nanoparticles of honokiol for enhancement of solubility and bioavailability. Moreover, the honokiol nanoparticles obtained were investigated and evaluated in terms of morphology, physicochemical properties, saturation solubility, dissolution in vitro, bioavailability in vivo, toxicity, and the inhibitory effect on growth of HepG2 cells.ResultsThe obtained honokiol nanoparticles existed nearly in spherical shape and could be turned into amorphous structure by the LAP method. Moreover, the solubility of the honokiol nanoparticles was extremely higher than that of free honokiol, and the nanoparticle dissolution rate was also higher than that of free honokiol, which was about 20.41 times and 26.2 times than that of free honokiol in artificial gastric juice and in artificial intestinal juice. The area under the curve [AUC(0–t)] value of honokiol nanoparticles was about 6.52 times greater than that of free honokiol; therefore, the honokiol nanoparticles had a higher bioavailability than free honokiol but were innoxious to the organs of rats. Additionally, the honokiol nanoparticles exhibited a higher inhibition of HepG2 cells due to their lower IC50 compared to free honokiol.ConclusionHonokiol nanoparticles have high solubility and bioavailability, and can become a new oral drug formulation and produce a better response for its clinical applications.

Honokiol: A Review of Its Anticancer Potential and Mechanisms

“…Due to the low water solubility and bioavailability of honokiol, multiple studies have been performed to develop proper honokiol delivery systems to improve its pharmacological effectiveness. A few studies have been performed to develop efficient drug carriers to deliver honokiol to its respective target, including the development of nanoparticles [224][225][226], micelles [227][228][229], and liposomes [73,171,223].…”

<p>Design, Formulation and in vivo Evaluation of Novel Honokiol-Loaded PEGylated PLGA Nanocapsules for Treatment of Breast Cancer</p>

“…The solubility of HK in different oils was determined by using a UV spectrophotometer (Model UV-1601 PC; Shimadzu, Kyoto, Japan) and measuring the absorbance at 294 nm. 24 The amount of soluble HK was estimated according to relevant standard plots. Standard plots were obtained after testing the solubility of five different concentrations of HK (0.1, 0.2, 0.4, 0.6 and 0.8 mg/mL) in each oil type separately.…”

“…Secondly, the amount of non-encapsulated HK in the supernatant after purification of NCs suspension was determined by high-performance liquid chromatography technique (HPLC) according to the previously reported method. 24 100 μL of the NCs preparations were diluted by the mobile phase. The amount of free HK was analyzed using HPLC equipment (Waters ® C18-5 column mm, 5 µm).…”

“…HK concentration was assessed by HPLC method as previously reported. 24 In vitro Stability HK-loaded NC preparations were sealed in glass vials and stored in the desiccator at room temperature of 25°C. The stability of HK-loaded NC lyophilized-powders (F1, F4, and F7) was tested every time intervals of 0, 2, 4 and 6 months after preparation to determine the sample size, PDI, zeta-potential and % E.E of NC formulations.…”

“…12,20 Several attempts are described to develop different carriermediated drug delivery strategies for HK based on nanotechnology. These nano-drug delivery systems include nanosuspension, 21 nanoparticles, [22][23][24] microbubbles, 25 liposomes 26 and polymeric micelles. 27,28 Recently, very few studies tried quantum dotsbased nanocapsules for co-delivery of honokiol and other anticancer drugs for theranostic applications.…”