Novel oral nano-in-microsystem delivers efficient curcumin delivery to relieve ulcerative colitis

Ulcerative colitis (UC) is an inflammatory disease of the distal colon that affects the gastrointestinal tract. This disease lasts for a long time and often comes back.

Patients with UC require long-term treatment to control disease progression. Several types of medications, such as salicylic acid, immunosuppressants, biologics, probiotics, antibiotics, and sulfasalazine, are used to treat UC. Scientists have reported that serious side effects are associated with current UC therapies.

Background

The Food and Drug Administration (FDA) has deemed curcumin (Cur) safe for oral administration. Cur is a naturally occurring bioactive compound, obtained from the rhizome of Curcuma longa L. (turmeric), which is rich in polyphenol. This compound possesses strong anti-inflammatory properties that have been shown to be effective against UC.

The anti-inflammatory effects of Cur, associated with Mitogen-Activated Protein Kinase (MAPK), Peroxisome Proliferator-Activated Receptor (PPAR-γ), and Nuclear Factor Kappa-B (NF-KB) signaling pathway regulation, have been exploited for CU treatment . Some of the limitations that hinder the application of Cur for UC treatment include its crystalline nature, instability in the gastrointestinal tract, strong hydrophobicity, and good intestinal metabolic ratio.

Recently, several nano-based systems have been designed for UC treatment. This treatment system improves bioavailability, drug solubility, pharmacokinetics, ability to efficiently target cells for inflammation and reduces systemic toxicity. During UC treatment, the nano-based drug delivery system containing modified nanoparticles can efficiently target macrophages and release Cur via endocytosis mediated by CD44. However, some of the limitations associated with this approach are the degradation of bioactive compounds, the drug burst process, and the early uptake of nanoparticles that can lead to adverse effects.

Previous studies have reported that polysaccharide-based microparticles (MPs) exhibit an intelligent colonic response; for example, it has a pH sensitivity. Natural polysaccharides, such as alginate (negatively charged) and chitosan (positively charged), are recognized by the FDA as safe and are used to synthesize MPs. These MPs are used for the development of an oral colon specific drug delivery system.

In the oral system of nanoparticles into microparticles (NMPs), MPs protect nanoparticles from enzymatic degradation until they reach the target cells. Recently, scientists have designed a new colonic targeting oral delivery system based on NMPs, containing Cur, for UC treatment. This study is available as a pre-proof in Materials & Design†

About the study

Researchers loaded NPs with Cur using negatively charged hyaluronic acid (HA) cross-linked with zein nanoparticles via self-assembly. Zein is a natural protein carrier, composed of hydrophobic amino acids, which can encapsulate hydrophobic chemical compounds. In this study, researchers synthesized core-shelled structured [email protected]/zein nanoparticles that showed a homogeneous distribution. These structures were studied using a scanning electron microscope (SEM) and transmission electron microscope (TEM). The size of [email protected]/zein nanoparticles were found to be 148.64 nm with a polydispersity index (PDI) of less than 0.4.

Scientists have revealed that analysis of the molecular interaction between the drug compound and its carrier is essential to establish a drug release profile. X-ray powder diffraction was performed to determine the variations of crystal morphological features of Cur in nanoparticles. The authors observed a sharp crystal diffraction peak of Cur, indicating appropriate crystallinity in Cur powder. However, no characteristic diffraction peaks were observed in [email protected]/zein nanoparticles, indicating a significant decrease in crystalline structure. In the [email protected]/zein nanoparticle group, Cur is physically encapsulated in nanoparticles via hydrogen bonding and electrostatic adsorption.

The authors have developed a strategy to prevent unwanted drug delivery [email protected]/zein nanoparticles, during their transit through the early small intestine and stomach. To achieve this, they embedded the nanoparticles in Alginate/Chitosan hydrogel microparticles to develop NPs-in-MPs by the electrospray technique. Researchers identified some of the electrospray parameters that affect [email protected] assembly, including viscosity, surface tension and nozzle diameter of electrospray. Previous studies have shown that chitosan improves the gut retention effect of the hydrogel MPs.

The mean diameter of the oral hydrogel microparticles considered in this study was 200 m. Researchers stated that the alginate was the main structure of the hydrogel microparticles. In this study, 0.1% calcium chloride concentration was used for the synthesis of hydrogel MPs. At intestinal pH, swelling of alginate hydrogels occurs leading to a charge reversal of chitosan to negative and subsequent release of encapsulated [email protected]/ if nanoparticles occur.

Importantly, researchers in this study noted that Cur/NMPs were stable in the stomach and small intestine; however, a rapid release of Cur took place in the colon. This observation suggests that the MPs possess colon-specific drug delivery characteristics. The HA-CD44 receptor recognition allows a higher uptake of [email protected]/zein nanoparticles in macrophages. In addition, the newly designed NMPs showed significant bioadhesive ability and colonic retention in colonic tissues. Researchers reported that oral administration of [email protected] revealed a significant improvement in colitis symptoms in dextran sodium sulfate (DSS)-induced UC mice by restricting the TLR4/NF-KB pathway.

Conclusion

The present study showed that the newly designed oral nano-in-micro hydrogel delivery platform can be efficiently used to deliver Cur for the treatment of UC. One of the main advantages of this drug delivery platform is that it is composed of all-natural and non-toxic materials. The authors believe that their strategy of combining MPs and nanomaterials can be used to formulate edible compounds for UC prevention and treatment.