Cytotoxic and antiangiogenic paclitaxel solubilized and permeation-enhanced by natural product nanoparticles

Abstract

Paclitaxel (PTX) is one of the most potent intravenous chemotherapeutic agents to date, yet an oral formulation has been problematic due to its low solubility and permeability. Using the recently discovered solubilizing properties of rubusoside (RUB), we investigated this unique PTX-RUB formulation. Paclitaxel was solubilized by RUB in water to levels of 1.6 to 6.3 mg/mL at 10 to 40% weight/volume. These, nanomicellar, PTX-RUB complexes were dried to a powder which was subsequently reconstituted in physiologic solutions. After 2.5 hrs in gastric fluid 85 to 99% of PTX-RUB remained soluble, while 79 to 96% remained soluble in intestinal fluid. The solubilization of PTX was mechanized by the formation of water-soluble spherical nanomicelles between PTX and RUB with an average diameter of 6.6 nm. Compared with Taxol®, PTX-RUB nanoparticles were nearly four times more permeable in Caco-2 cell monocultures. In a side-by-side comparison with DMSO-solubilized PTX, PTX-RUB maintained the same level of cytotoxicity against three human cancer cell lines with IC50 values ranging from 4 nM to 20 nM. Additionally, tubular formation and migration of HUVECs were inhibited at levels as low as 5 nM. These chemical and biological properties demonstrated by the PTX-RUB nanoparticles may improve oral bioavailability and enable further pharmacokinetic, toxicologic, and efficacy investigations.

Enzymatic Production of Steviol Glucosides Using β-Glucosidase and Their Applications

“…They published that paclitaxel solubility in water can be increased from 1.6 to 6.3 mg/mL with 10%-40% Ru at a particle size of 6.6 nm. In addition, over 80% of this complex has remained soluble in the gastric and intestinal fluids (Liu et al, 2015). Moreover, compared to taxol, the complex of paclitaxel-Ru has almost four times greater permeability in the Caco-2 cell monoculture (Liu et al, 2015) (Table 23.3).…”

“…In addition, over 80% of this complex has remained soluble in the gastric and intestinal fluids (Liu et al, 2015). Moreover, compared to taxol, the complex of paclitaxel-Ru has almost four times greater permeability in the Caco-2 cell monoculture (Liu et al, 2015) (Table 23.3). Nguyen et al have reported that Ru can enhance the liquiritin solubility in water from 0.98 to 4.7 mg/mL (Nguyen et al, 2014).…”

Rubusoside alleviates the ovalbumin‐induced mice allergic asthma by modulating the NF‐κB activation

“…Rubusoside (Rbs) is a diterpene glycoside found primarily in the leaves of Rubus suavissimus (Chinese sweet tea), which is developed into a natural sweetener in the application of food manufacturing (Koh, Chou, & Liu, 2009). Recent studies have reported that Rbs is the manifestation of many biological properties, such as anticancer (Liu et al, 2015; Zhang, Dai, et al, 2017), antiangiogenic (Liu et al, 2015), and anti‐obesity (Koh et al, 2011) effects, which can be used to protect against palmitic acid‐induced lipotoxicity in pancreatic INS‐1 cells (Zheng et al, 2019). In addition, as is reported by relevant studies, Rbs can reduce the transport of human glucose transporters (GLUT)‐1 and fructose GLUT‐5 (George Thompson, Iancu, Nguyen, Kim, & Choe, 2015) and inhibition of the activity of NF‐κB and α‐amylase in vitro (Li, Tanaka, Zhang, Yang, & Kouno, 2007; Liu, Gao, Zhang, Ye, & Liu, 2005).…”

A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy

“…It was a well-known natural sweetening agent and had been used in food and beverage products. Recently, RUB has been increasingly attracting attention for its solubilizing properties [ 17 – 20 ]. However, the solubilization mechanism of RUB is still unclear until now.…”