Preparation, characterization, and evaluation of the antitumor effect of kaempferol nanosuspensions

Abstract

Kaempferol (KAE) is a natural avonoid compound with antitumor activity. However, the low aqueous solubility, poor chemical stability and suboptimal bioavailability greatly restricted its clinical application of cancer. In order to overcome these shortages and enhance the antitumor effect of KAE, we developed a kaempferol nanosuspensions (KAE-NSps) with D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) as stabilizer, screened the optimal preparation process, and investigated the basic properties and the antitumor effect in the study. The results demonstrated that the particle size was 186.6 ± 2.6 nm of the TPGS-KAE-NSps optimized, the shape of which was fusiform under the transmission electron microscope. The 2% (w/v) glucose was used as the cryoprotectant for TPGS-KAE-NSps, whose drug loading content was 70.31 ± 2.11%, and the solubility was improved prominently compared to KAE. The stability and biocompatibility of TPGS-KAE-NSps were favorable, which had a certain sustained release effect. Moreover, TPGS-KAE-NSps clearly seen to be taken in the cytoplasm exhibited a stronger cytotoxicity and suppression of cell migration, higher apoptosis rate and more intracellular ROS production compared to KAE in vitro cell experiments. In addition, TPGS-KAE-NSps showed a stronger inhibition of tumor growth (the tumor inhibition rate of high dose intravenous injection group was 68.9 ± 1.46%) than KAE with no obvious toxicity on 4T1 tumor-bearing mice. Overall, TPGS-KAE-NSps prepared improved the defect and the antitumor effect of KAE notably, which was a promising nanodrug delivery system for KAE and was expected to become a clinical antitumor drug.

"Optimizing Pharmaceutical Formulations: Advancements in Nanosuspension Pre-Formulation to Enhance Solubility and Bioavailability of Active Agents"

“…Regression analysis of equation (3) shows that the coefficient of G is positive and B is positive. This indicates that when the amount of Poloxamer 407 (A) increases, the viscosity percentage also increases.…”

“…Nanosuspensions are composed of medication particles that are only a few nanometres in size and are stabilized in a dispersion medium. [3][4] These suspensions provide faster dissolving rates and better absorption into the body, resulting in higher bioavailability. Although there have been significant breakthroughs in medication delivery using nanotechnology, there is still a lack of study in comprehending the important connection between pre-formulation studies and the effective creation of nanosuspensions.…”

Lipid-Based Nanoparticles in Delivering Bioactive Compounds for Improving Therapeutic Efficacy

“…In addition, TPGS-KAE-NS exhibited favorable stability and biological compatibility, contributing to a sustained release profile. A greater cytotoxicity, cell migration, and intracellular generations of ROS were demonstrated by TPGS-KAE-NS in vitro cell tests compared with those of pure kaempferol [ 90 ]. To tackle the bioavailability issue, Ilk and colleagues fabricated lecithin-chitosan nanoparticles (LCNPs) of kaempferol to evaluate antifungal efficacy against the phytopathogenic fungus Fusarium oxysporium , compared with pure kaempferol.…”