Current Issue : July-September Volume : 2025 Issue Number : 3 Articles : 5 Articles
Background: Ulcerative colitis (UC), a subtype of chronic inflammatory bowel disease (IBD), is primarily treated with oral medications to reduce inflammation and alleviate symptoms. Celecoxib (CXB) is an attractive candidate for UC; however, its limited solubility and low bioavailability pose significant challenges to its clinical application. Methods: We reported a novel chondroitin sulfate A–Celecoxib (CSA-CXB) polymeric nanoprodrug to address the limited solubility and low bioavailability of CXB. CXB was conjugated to chondroitin sulfate A (CSA) via succinic anhydride (SA) and ethylenediamine to prepare CSA-CXB polymers, which can self-assemble into nanoparticle structural prodrugs in aqueous condition. We investigated the stability, blood compatibility, and responsiveness of the nanoparticles. The ability of the nanoparticles to treat UC in vitro and in vivo was then evaluated. Results: The CSA-CXB nanoprodrug was spherical with a mean particle size of 188.4 ± 2.2 nm, a zeta potential of −22.9 ± 0.1 mV, and sustained drug release behavior. Furthermore, CSA-CXB exhibited remarkable antioxidant and anti-inflammatory effects, as it can significantly increase the free radical scavenging rate and reduce the expression level of ROS, TNF-α, IL-6, nitric oxide (NO), and COX-2 protein in vitro. In vivo results demonstrated that CSA-CXB targeted the mice’s colon efficiently mitigate UC symptoms by inhibiting the expression of inflammatory cytokine. Conclusions: The CSA-CXB nanoprodrug can improve the therapeutic impact of CXB, and has potential as a new preparation for a clinical UC treatment nanoprodrug....
It is reported that poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) coated with chitosan and its derivatives, such as glycol chitosan (GC), can enhance the targeted uptake of PLGA NPs by intestinal epithelial cells. However, the optimal amount of GC for coating and the specific mechanisms by which it facilitates PLGA endocytosis remain unclear. In this study, PLGA-NPs are prepared using either single- or double-emulsion methods and coated with varying amounts of GC. The results confirmed that GC-coated PLGA NPs are internalized via both clathrin-mediated and caveolae-mediated endocytosis, whereas uncoated NPs relied on only clathrin-mediated endocytosis in Caco-2 and HT-29 cells. The optimized GC-coated PLGA-NPs formulation is further modified by layering alginate to enhance the oral delivery of insulin. In subsequent in vivo studies, the GC and alginate-coated PLGA NPs demonstrated stability and prolonged efficacy, achieving approximately a 50% reduction in blood glucose levels at 6 h post-administration in streptozotocin-induced diabetic mice. These findings provide compelling evidence of the optimal coating amount and molecular mechanisms for GC in the PLGA oral platform, underscoring the feasibility and commercial potential of oral delivery platform based on the optimized GC- and alginate-coated PLGA NPs....
Over the past decade, new technologies have emerged to increase intrinsic potency, enhance bioavailability, and improve targeted delivery of drugs. Most pharmaceutical formulations require multiple dosing due to their fast release and short elimination kinetics, increasing the risk of adverse events and patient non-compliance. Due to these limitations, enormous efforts have focused on developing drug delivery systems (DDSs) for sustained release and targeted delivery. Sustained release strategies began with pioneering research using silicone rubber embedding for small molecules and non-inflammatory polymer encapsulation for proteins or DNA. Subsequently, numerous DDSs have been developed as controlled-release formulations to deliver systemic or local therapeutics, such as small molecules, biologics, or live cells. In this review, we discuss the latest developments of DDSs, specifically nanoparticles, hydrogels, and microgrippers for the delivery of systemic or localized drugs to the gastrointestinal (GI) tract. We examine innovative DDS design and delivery strategies tailored to the GI tract’s unique characteristics, such as its extensive length and anatomical complexity, varying pH levels and enzymatic activity across different sections, and intrinsic peristalsis. We particularly emphasize those designed for the treatment of inflammatory bowel disease (IBD) with in vivo preclinical studies....
Silibinin (C25H22O10), a notable bioactive flavonolignans, is recognized for its anticancer properties. However, due to its poor water solubility, the objective of this study was to design and synthesize nanocarriers to enhance the solubility of silibinin for effective delivery to AGS gastric cancer cells. This study details the synthesis of PEG400- OA nanoparticles for silibinin delivery to AGS cells. Various physicochemical techniques, including FT- IR, TGA, EDX, FE- SEM, and TEM, were employed to characterize the silibinin- loaded nanoparticles (SLNs), confirming particle size, elemental composition, thermal stability, and paramagnetic properties. The anticancer effects of the SLNs were assessed using MTT assay, scratch test, and Q- RT- PCR. The SLNs exhibited particle sizes ranging from 45 to 60 nm, with thermal stability below 110°C. TEM images suggested a micelles/liposomes structure due to the low polydispersity and spherical shape of the particles. EDX analysis revealed the presence of C, O, N, and P, confirming the incorporation of phospholipids (micelle/liposome) within the SLNs. The IC50 of SLNs in AGS cells was determined to be 28.21 μg/mL. Antimigration effects of SLNs's were demonstrated through the downregulation of miR- 181a and upregulation of its potential targets (TGFB, SMAD3, and β- catenin genes), as well as the upregulation of miR- 34a and downregulation of its potential target (E- Cadherin antimigration gene). The findings suggest that nanoparticles serve as effective nanocarriers for the targeted delivery of silibinin to cancer cells. Silibinin- loaded micelles/liposomes nanoparticles (SLNs) appear to inhibit cancer cell proliferation and migration by modulating the expressionof miRNAs and their target mRNAs....
Colorectal cancer (CRC) remains a highly heterogeneous malignancy with significant morbidity and mortality worldwide. Despite advancements in surgery, chemotherapy, immunotherapy, and targeted therapy, treatment efficacy is often hampered by drug resistance and systemic toxicity. In recent years, nano-drug delivery systems (NDDS) have emerged as a promising strategy to enhance therapeutic precision, reduce adverse effects, and overcome resistance in CRC treatment. This review discusses the recent advancements in NDDS for CRC treatment, focusing on the optimization of oral drug delivery systems, the development of tumor-specific targeting strategies, and the design of intelligent delivery systems responsive to the tumor microenvironment (TME). Furthermore, we summarize current challenges in NDDS translation and explore future research directions for enhancing their clinical feasibility and therapeutic impact....
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