Researchers from Northern Border University in Saudi Arabia have developed a rhein-loaded self-nano emulsifying drug delivery system (RS-SNEDDS), significantly enhancing the compound's solubility, bioavailability, and therapeutic potential, particularly for neurological applications.
In a recent study, a team of researchers from Northern Border University in Arar, Saudi Arabia, led by Md Ali Mujtaba, has made significant advancements in drug delivery technology by developing a rhein-loaded self-nano emulsifying drug delivery system (RL-SNEDDS) (1). With this study, the researchers sought to deal with the challenge of rhein's poor aqueous solubility and low bioavailability. This study, which was published in the International Journal of Nanomedicine, helps to advance therapeutics, offering a way to improve these applications.
Rheum palmatum or Chinese rhubarb, in the garden. | Image Credit: © beres - stock.adobe.com
Rhein is a bioactive lipophilic compound with diverse pharmacological properties, including hepatoprotective, nephroprotective, anti-cancer, and anti-inflammatory (1–3). Rhein is often found medicinal herbs like Rheum palmatum, Cassia tora, Polygonum multiflorum, and Aloe barbadensis (4). Because it has been used in Chinese medicine for over 1,000 years, its health-related biological activities are of interest to researchers (4).
This study delves into rhein more extensively, and it offers a pathway of how it can be used to improve therapeutic applications. However, its limited water solubility and low systemic absorption have hindered its clinical application. To overcome these limitations, the researchers designed RL-SNEDDS using an aqueous titration method with eucalyptus oil as the oil phase, Tween 80 as the surfactant, and PEG 400 as the co-surfactant (1).
In the study, the researchers optimized the formulation by using a 32 factorial design. Then, advanced spectroscopic techniques were used to analyze RL-SNEDDS and its properties. For their study, the research team used Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), powdered X-ray diffraction (pXRD), and field emission scanning electron microscopy (SEM) to accomplish this objective (1).
The formulation was then transformed into a solid-state version (RS-SNEDDS) to enhance its stability. The RL-SNEDDS the researchers altered showcased some key characteristics, including its zeta potential (−24.6 mV ± 0.34), average droplet size (129.3 ± 1.57 nm), and encapsulation efficiency (98.86 ± 0.23%) (1). Differential scanning calorimetry and pXRD confirmed reduced drug crystallinity, SEM revealed smooth, spherical nanosized globules, essential for prolonged drug release (1).
The researchers conducted in vivo pharmacokinetic studies on Sprague-Dawley rats to evaluate the oral bioavailability and brain tissue concentration of RS-SNEDDS (1).
Compared to free rhein suspension, the optimized RS-SNEDDS demonstrated a substantial increase in drug absorption and retention. For maximum concentration, RS-SNEDDS produced a result on 8 ± 0.930 μg/mL compared to 1.96 ± 0.712 μg/mL (free rhein suspension (1).
Furthermore, RS-SNEDDS showed enhanced brain tissue penetration, with a maximum concentration of 2.90 ± 0.171 μg/mL and an area under the curve (AUC) of 18.18 ± 1.68 μg/mL·hr (1). These findings suggest that RS-SNEDDS significantly improves rhein's ability to reach and maintain effective concentrations in the brain, a critical factor for treating neurological conditions (1).
This delivery system helped fulfill two objectives. First, it helped rhein’s bioavailability and solubility, and second, it opens new routes to use it in neurological and systemic therapies (1). The prolonged drug release observed with RS-SNEDDS suggests potential for reducing dosing frequency, thereby improving patient compliance.
Although the study provides compelling evidence of RS-SNEDDS’s efficacy, further research is needed to evaluate its clinical applications in humans. The team also emphasized the potential for adapting similar nanoemulsion-based systems for other poorly soluble drugs, broadening the scope of nanomedicine (1).
By addressing critical solubility and bioavailability challenges, the researchers have laid the groundwork for more efficient and targeted drug delivery systems.
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