The current study sought to create graphene oxide-based superstructures for gastrointestinal drug delivery. Graphene oxide has a large surface area that can be used to load anti-cancer drugs via non-covalent methods such as surface adsorption and hydrogen bonding. To enhance the bio-applicability of graphene oxide, nano-hybrids were synthesized by encapsulating the graphene oxide into calcium alginate hydrogel beads through the dripping-extrusion technique. These newly developed bio-nanocomposite hybrid hydrogel beads were evaluated in structural analysis, swelling study, drug release parameters, haemolytic assay, and antibacterial activity. Doxorubicin served as a model drug. The drug entrapment efficiency was determined by UV-spectroscopy analysis and was found to be high at ⁓89% in graphene oxide hybrid hydrogel beads. These fabricated hydrogel beads ensure the drug release from a hybrid polymeric matrix in a more controlled and sustained pattern avoiding the problems associated with a non-hybrid polymeric system. The drug release study of 12 h shows about 83% release at pH 6.8. In vitro drug release kinetics proved that drug release was a Fickian mechanism. The cytotoxic effect of graphene oxide hybrid alginate beads was also determined by evaluating the morphology of bacterial cells and red blood cells after incubation. Additionally, it was determined that the sequential encapsulation of graphene oxide in alginate hydrogel beads hides its uneven edges and lessens the graphene oxide's negative impacts. Also, the antibacterial study and biocompatibility of fabricated hydrogel beads made them potential candidates for gastrointestinal delivery.
Targeting the small intestine employing nanotechnology has proved to be a more effective way for site-specific drug delivery. The drug targeting to the small intestine can be achieved via nanoparticles for its optimum bioavailability within the systemic circulation. The small intestine is a remarkable candidate for localized drug delivery. The intestine has its unique properties. It has a less harsh environment than the stomach, provides comparatively more retention time, and possesses a greater surface area than other parts of the gastrointestinal tract. This review focuses on elaborating the intestinal barriers and approaches to overcome these barriers for internalizing nanoparticles and adopting different cellular trafficking pathways. We have discussed various factors that contribute to nanocarriers' cellular uptake, including their surface chemistry, surface morphology, and functionalization of nanoparticles. Furthermore, the fate of nanoparticles after their uptake at cellular and subcellular levels is also briefly explained. Finally, we have delineated the strategies that are adopted to determine the cytotoxicity of nanoparticles.
The aim of present research aims to fabricate a system of enteric coating of hydrogel beads with pH-sensitive polymer, which shows solubility at pH > 7, and explore their potential to target the colon for drug delivery. Hydrogel beads were fabricated through the extrusion-dripping technique followed by ion gelation crosslinking. Moreover, freeze-thaw cycle was implemented for crosslinking of polyvinyl alcohol (PVA)/Ca-alginate blend beads. The oil-in-oil solvent evaporation method was adopted for the Eudragit coating of hydrogel beads using different coat: core ratios (4:1 or 8:1). Coated and uncoated hydrogel beads were evaluated by in vitro physicochemical properties, swelling and drug release behaviours, and in vivo pharmacokinetics, swelling, and toxicity evaluation. Diclofenac sodium was loaded as an experimental drug. Drug entrapment efficiency for the PVA/Ca-alginate beads was calculated as 98%, and for Ca-alginate beads, it came out to a maximum of 74%. Drug release study at various pH suggested that, unlike uncoated hydrogel beads, the coated beads delay the release of diclofenac sodium in low pH of the gastric and intestinal environment, thus targeting the colon for the drug release. It was concluded that Eudragit S-100-coated hydrogel beads could serve as a more promising and reliable way to target the colon for drug delivery.Graphical abstract.
The tumor-specific targeting of chemotherapeutic agents for specific necrosis of cancer cells without affecting the normal cells poses a great challenge for researchers and scientists. Though extensive research has been carried out to investigate chemotherapy-based targeted drug delivery, the identification of the most promising strategy capable of bypassing non-specific cytotoxicity is still a major concern. Recent advancements in the arena of onco-targeted therapies have enabled safe and effective tumor-specific localization through stimuli-responsive drug delivery systems. Owing to their promising characteristic features, stimuli-responsive drug delivery platforms have revolutionized the chemotherapy-based treatments with added benefits of enhanced bioavailability and selective cytotoxicity of cancer cells compared to the conventional modalities. The insensitivity of stimuli-responsive drug delivery platforms when exposed to normal cells prevents the release of cytotoxic drugs into the normal cells and therefore alleviates the off-target events associated with chemotherapy. Contrastingly, they showed amplified sensitivity and triggered release of chemotherapeutic payload when internalized into the tumor microenvironment causing maximum cytotoxic responses and the induction of cancer cell necrosis. This review focuses on the physical stimuli-responsive drug delivery systems and chemical stimuli-responsive drug delivery systems for triggered cancer chemotherapy through active and/or passive targeting. Moreover, the review also provided a brief insight into the molecular dynamic simulations associated with stimuli-based tumor targeting.