Ulcerative colitis (UC) is an inflammatory disease of the distal colon, which affects the gastrointestinal tract. This disease persists for an extended period of time and is often repeated.
Patients with UC need long-term treatment to control disease progression. Various types of drugs are used for the treatment of UC, such as salicylic acid, immunosuppressive agents, biological drugs, probiotics, antibiotics and sulfasalazine. Scientists have reported that serious side effects are associated with current UC therapies.
Study: Nano-in-micro alginate / chitosan hydrogel using electrospray technology for oral curcumin delivery to effectively relieve ulcerative colitis. Image credit: Alona Siniehina / Shutterstock
Fund
The Food and Drug Administration (FDA) has considered curcumin (Cur) to be safe for oral administration. Cur is a natural bioactive compound, obtained from the rhizome of Curcuma longa L. (turmeric), which is rich in polyphenols. This compound possesses high anti-inflammatory properties that have been found to be effective against UC.
The anti-inflammatory effects of Cur, associated with the regulation of the Kappa-B nuclear factor (NF-κB) signaling pathway, have been exploited for the treatment of UC. However, some of the limitations that hinder the application of Cur for the treatment of UC include its crystalline nature, instability in the gastrointestinal tract, strong hydrophobicity, and large intestinal metabolic rate.
Recently, several nano-based systems have been designed for the treatment of UC. This treatment system improves bioavailability, drug solubility, pharmacokinetics, the ability to efficiently target cells with inflammation, and decreases systemic toxicity. During treatment with UC, the nanoparticle-based drug delivery system containing modified nanoparticles can efficiently target macrophages and release Cur by endocytosis under the mediation of CD44. However, some of the limitations associated with this approach are the degradation of bioactive compounds, the process of blast drug release, and the early absorption of nanoparticles that can cause adverse effects.
Previous studies have reported that polysaccharide-based microparticles (MPs) exhibit a colonic intelligent response; for example, it possesses pH sensitivity. Natural polysaccharides, such as alginate (negatively charged) and chitosan (positively charged), have been recognized by the FDA as safe and are used to synthesize MP. These MPs are used for the development of a specific drug delivery system for the oral colon.
In the oral microparticle nanoparticle (NMP) system, MPs protect nanoparticles from enzymatic degradation until they reach the target cells. Recently, scientists have designed a new NMP-based oral colon delivery delivery system, containing Cur, for the treatment of UC. This study is available as a preliminary test in Materials and Design.
About the study
The researchers loaded NP with Cur using negatively charged crosslinked hyaluronic acid (HA) with zein nanoparticles using self-assembly. Zein is a natural protein transporter, composed of hydrophobic amino acids, that can encapsulate hydrophobic chemical compounds. In this study, the researchers synthesized structured with basic shell [email protected]nanoparticles of / zein that presented a homogeneous distribution. These structures were studied using a scanning electron microscope (SEM) and a transmission electron microscope (TEM). The size of [email protected]Nanoparticles / zein were determined to be 148.64 nm with a polydispersity index (PDI) of less than 0.4.
The scientists revealed that analysis of the molecular interaction between the drug compound and its carrier is essential to establish a drug release profile. Powder X-ray diffraction was performed to determine variations in the morphological characteristics of Cur crystals within nanoparticles. The authors observed a sharp peak crystal diffraction peak of Cur indicating adequate crystallinity to Cur powder. However, no characteristic diffraction peaks were observed [email protected]nanoparticles / zein, which indicates a significant decrease in crystal structure. In the [email protected]nanoparticle group / ze, Cur has been physically encapsulated in nanoparticles using hydrogen bonds and electrostatic adsorption.
The authors designed a method to prevent unwanted drug release [email protected]nanoparticles of / zein, during their transit through the small intestine and stomach. To achieve this, they embedded the nanoparticles within alginate / chitosan hydrogel microparticles to develop NPs-in-MPs using the electrospray technique. The researchers identified some of the electrospray parameters they affect [email protected] assembly, including viscosity, surface tension, and electrospray nozzle diameter. Previous studies have shown that chitosan enhances the intestinal retention effect of hydrogel MPs.
The mean diameter of the oral hydrogel microparticles considered in this study was 200 μm. The researchers claimed that alginate was the main structure of hydrogel microparticles. In this study, a calcium chloride concentration of 0.1% was used for the synthesis of hydrogel MP. At intestinal pH, there is a swelling of the alginate hydrogels leading to a negative charge reversal of the chitosan and subsequently to the release of encapsulated hydrogels. [email protected]nanoparticles are produced / ze.
Importantly, in this study, the researchers observed that Cur / NMPs were stable in the stomach and small intestine; however, there was a rapid release of Cur in the colon. This observation suggests that MPs possess colon-specific drug release characteristics. Recognition of the HA-CD44 receptor allows for greater uptake of [email protected]/ Zein nanoparticles in macrophages. In addition, newly designed NMPs showed significant colonic bioadhesion and retention capacity in colon tissues. The researchers reported that the oral administration of [email protected] revealed a significant improvement in colitis symptoms in UC mice induced by Dextran Sodium Sulfate (DSS) by restricting the TLR4 / NF-κB pathway.
Conclusion
The current study showed that the newly designed nano-in-micro hydrogel delivery platform could be used efficiently to deliver Cur for UC treatment. One of the main advantages of this drug delivery platform is that it is made of all-natural, non-toxic materials. The authors believe that their strategy for combining MP and nanomaterials could be used to formulate edible compounds for the prevention and treatment of UC.
Magazine reference:
Zang, C. et al. (2022) Nano-in-micro alginate / chitosan hydrogel using electrospray technology for oral curcumin delivery to effectively relieve ulcerative colitis. Materials and Design. two: