Search Results (10,853)

Currently, GLP-1RAs are peptide drugs, typically administered by injection due to insufficient absorption, and only one GLP-1RA, semaglutide, is available as an orally administered drug. To overcome the absorption challenges of oral peptides, this drug product contains the absorption enhancer SNAC. As the tablet is eroded in the stomach, SNAC neutralizes the acidic gastric environment, thereby protecting the semaglutide from enzymatic degradation. Then, SNAC fluidizes the stomach lipidic membrane to increase semaglutide transcellular permeability across the gastric epithelium. It is necessary to realize that the use of such a unique drug product, that relies solely on the stomach for absorption, is expected to be affected by the extreme gastric anatomy/physiology changes post-MBS. Hence, we analyzed the key mechanisms that may affect the bioavailability of oral semaglutide post-MBS. Several mechanisms appear to potentially reduce oral semaglutide absorption post-MBS, including decreased inner gastric surface area, decreased gastric contractility, and faster gastric emptying. Hence, the effectiveness of the complex formulation, that relies solely on the stomach for the SNAC activity and semaglutide absorption, may be severely hampered post-MBS; clinicians should be aware of the potential malabsorption of oral GLP-1RA post-MBS, and preferably consider subcutaneous therapy until specific pharmacokinetic/clinical data are available. Full article

Dihydroartemisinin (DHA), the active metabolite of artemisinin derivatives, is a clinically established antimalarial agent that has recently gained significant attention for its anticancer properties. This review systematically examines the molecular mechanisms underlying DHA’s antitumor effects and explores innovative strategies to enhance its bioavailability and therapeutic efficacy. DHA demonstrates substantial potential in combination therapies with conventional clinical agents, with its broad anticancer applications being strongly supported by both preclinical and clinical evidence. Furthermore, this article outlines future research directions, discusses challenges in clinical translation, and summarizes current scientific approaches addressing these limitations. Collectively, this review highlights DHA’s promising role in cancer treatment and provides a foundation for developing improved therapeutic strategies. Full article

Antimicrobial peptides (AMPs) have re-emerged as promising anti-infective agents, particularly against multidrug-resistant bacteria; however, their therapeutic development remains constrained by proteolytic degradation, host cell toxicity, and rapid systemic clearance. Rather than focusing solely on sequence discovery, recent efforts have shifted toward structural and supramolecular modification strategies aimed at improving stability, selectivity, and pharmacological performance. This review critically analyzes intramolecular modifications—including phosphorylation, glycosylation, acetylation, methylation, and backbone cyclization—that modulate peptide conformation and resistance to enzymatic degradation. In parallel, extramolecular approaches such as PEGylation, lipidation, and conjugation to antibiotics, siderophores, or antibodies are examined in the context of enhanced targeting and prolonged bioavailability. Particular emphasis is placed on localized delivery systems, including hydrogels, polymeric films, and nanofibrous scaffolds, which enable spatially controlled administration and mitigate systemic exposure. By integrating evidence from ex vivo and in vivo infection models, this work delineates the translational potential and remaining bottlenecks of chemically engineered AMP platforms for skin and soft tissue infections. Full article

Background/Objectives: Women and girls, particularly in sub-Saharan Africa, face high risks for both HIV and unintended pregnancy. Inconsistent condom use underscores the need for new multipurpose prevention technologies (MPTs) that combine HIV pre-exposure prophylaxis (PrEP) and contraception. Long-acting (LA) injectables are especially promising. To this end, an LA cabotegravir (CAB)/medroxyprogesterone acetate (MPA) in situ-forming implant (ISFI) has been developed. We report pharmacokinetic (PK) modeling to characterize CAB and MPA disposition and absorption to support the development of the MPT ISFI. Methods: Female BALB/c mice received single intravenous (IV) or subcutaneous (SQ) bolus doses of CAB or MPA. Sparse plasma samples were collected (~3 mice/timepoint) for PK analysis by LC-MS/MS. Noncompartmental analysis assessed SQ bioavailability. Macroparameterized compartmental PK models were fit to IV data to derive unit impulse responses (UIRs) for each drug. Results: CAB and MPA exhibited 61% and 42% bioavailability, respectively. CAB IV PK was best described by a two-compartment model with macroconstant parameters: A = 16,621 ng/mL, α = 4.52 h⁻¹, B = 30,206 ng/mL, and β = 0.053 h⁻¹. MPA IV PK was also best described by a two-compartment model, with A = 2506 ng/mL, α = 10.5 h⁻¹, B = 439 ng/mL, and β = 0.65 h⁻¹. These values define the UIR for CAB and MPA. Conclusions: Our IV PK modeling framework fully characterizes CAB/MPA disposition in mouse, enabling downstream deconvolution-based estimation of absorption from controlled-release formulations. This provides a foundation for in vitro–in vivo correlation, facilitating preclinical evaluation of long-acting formulations such as ISFIs. Full article

Phosphogypsum (PG), a major by-product of the phosphate industry, has potential for improving acidic and nutrient-poor red soils, yet its agronomic benefits and heavy metal risks require systematic evaluation. A field experiment was conducted with five treatments, CK (soil only), GT (50% modified phosphogypsum, MPG), TT (40% MPG), ZT (50% phosphorite tailings), and DT (25% MPG + 25% lake sediment), to assess their effects on soil properties, enzyme activities, peanut growth, yield, quality, and heavy metal accumulation. All amendments improved soil structure, moisture retention, nutrient availability, and enzymatic activities. Peanut pod and kernel yields increased under all treatments, with DT achieving the greatest improvements (29.89% and 40.88%, respectively), whereas ZT showed the weakest response (1.91% and 6.26%). DT also achieved the highest soil quality index, and performed best in both yield improvement and root development. Although Cd accumulation increased under DT, heavy metal concentrations in peanut kernels remained below national food safety limits. Overall, DT was identified as the most effective amendment for enhancing red soil fertility and peanut productivity, while long-term monitoring of Cd bioavailability is recommended to ensure sustainable and safe application. Full article

Bisphenol A (BPA) is a widely used endocrine-disrupting chemical that has been linked to oxidative stress and inflammation. This study investigated whether carvacrol (CAR), a natural monoterpene with antioxidant potential, mitigates BPA-induced hepatorenal toxicity in rats. Forty-two male Wistar albino rats were allocated into six groups (n = 7/group): control, vehicle (corn oil), BPA (25 mg/kg/day), and BPA co-administered with CAR (12.5, 25, or 50 mg/kg/day) by oral gavage for 30 days. Oxidative status was assessed in liver and kidney homogenates by measuring malondialdehyde (MDA), reduced glutathione (GSH), and the activities of superoxide dismutase (SOD) and catalase (CAT). In addition, histopathological evaluations were performed, and pro-inflammatory gene expression (NF-κB, TNF-α, and IFN-γ) was quantified by RT-qPCR. BPA induced a consistent pro-oxidant pattern, including increased hepatic MDA with depleted antioxidant defenses, and upregulated inflammatory transcripts. Carvacrol attenuated these alterations in a dose-dependent manner, and the CAR50 group was associated with statistically supported improvements across the oxidative stress panel, pro-inflammatory transcript expression, and histopathology scores. Overall, these findings identify carvacrol as a candidate for further preclinical evaluation against BPA-triggered oxidative and inflammatory disturbances in vivo; however, human-relevant extrapolation will require careful attention to dose scaling, bioavailability, and metabolism. Full article

Marine-derived natural products are increasingly recognized for their therapeutic potential in cancer and other chronic diseases. Despite significant advances, current cancer treatments remain challenged by toxicity, drug resistance, and limited survival benefits. Natural compounds offer promising alternatives due to their multi-target mechanisms and favorable safety profiles. Among them, Spirulina, a filamentous cyanobacterium, stands out for its rich composition and diverse biological activities. Its anticancer effects involve apoptosis induction via intrinsic and extrinsic pathways, cell cycle arrest at G1/S or G2/M phases, inhibition of angiogenesis through the VEGF/VEGFR2 axis, and suppression of epithelial–mesenchymal transition. These activities are mainly attributed to C-phycocyanin, allophycocyanin, phenolic compounds, and immunomodulatory polysaccharides. Spirulina also exhibits potent immunomodulatory effects by enhancing natural killer cell activity, promoting M1 macrophage polarization, and regulating Th1 and Th17 cytokine responses, highlighting its potential as both an immunotherapeutic and chemoprotective agent. Moreover, preclinical findings suggest it may reduce chemotherapy-associated side effects. However, translation into clinical therapy remains limited by low bioavailability, lack of standardized extracts, and scarce clinical evidence. This review summarizes current mechanistic and immunological insights and highlights the need for optimized formulations, defined dosing strategies, and well-designed clinical trials to validate Spirulina’s potential in cancer treatment. Full article

Objectives: This review aims to systematically summarize turmeric’s botanical traits, traditional medicinal applications, phytochemical components and their biological activities, and to integrate botanical, phytochemical, molecular and clinical perspectives to provide a comprehensive theoretical foundation and practical guidance for the future scientific research and clinical applications of turmeric as a functional food. Methods: A systematic overview and comprehensive analysis were conducted on the existing research about turmeric, covering its botanical characteristics, traditional medicinal application value, the biological mechanisms of major bioactive compounds (especially curcumin), pharmacokinetic properties, and the latest progress in relevant clinical trials. Results: Turmeric has important historical and cultural significance in traditional medicine, and its major bioactive compound curcumin is the core of its therapeutic potential, which can modulate antioxidant, anti-inflammatory, and antitumor signaling pathways. Recent studies have found that curcumin exerts significant biological effects by regulating noncoding RNAs (ncRNAs) and epigenetic modifications, showing a promising role in cancer chemoprevention. Meanwhile, curcumin has specific pharmacokinetic properties, and current clinical trials on turmeric and curcumin have made certain progress, yet challenges such as low bioavailability and limited therapeutic efficacy still exist. Conclusions: Turmeric, as a widely recognized functional food with rich phytochemicals and diverse biological activities, has great potential in scientific research and clinical application, especially in cancer chemoprevention. Solving the key challenges such as curcumin’s bioavailability and therapeutic efficacy is the core direction for the future development and utilization of turmeric, and the multi-dimensional research perspective can provide more comprehensive support for its practical application as a functional food. Full article

Astaxanthin (AST), despite its high bioactivity, exhibits poor stability and low bioavailability due to its strong lipophilicity and inherent degradation susceptibility. To overcome such a challenge, we developed a food-grade oleogel delivery system using a soy protein–arabinoxylan (SA) glycosylated complex modulated by different concentrations (0.5–3%) of sucrose ester (SE) or soy lecithin. We show that the emulsifier concentration has a non-linear effect on the oleogel microstructure: an optimal level of 1% had a significant impact on the interfacial compactness and network density, giving rise to improved thermal stability, rheological strength and AST encapsulation efficiency (81.27%). During in vitro digestion, the SA matrix in combination with emulsifiers allowed gastric protection and intestinal-targeted release of AST with a bioaccessibility of up to 88.84% (SAO-SE-AST). This controlled release profile directly translated into enhanced in vivo antioxidant efficacy in wild-type Bristol N2 Caenorhabditis elegans, as evidenced by reduced lipofuscin accumulation, elevated thermotolerance (survival rate: 64.44–73.33%), suppressed reactive oxygen species levels and activation of endogenous antioxidant enzymes (superoxide dismutase as well as glutathione peroxidase). Collectively, this research has uncovered that food-grade emulsifiers are not only stabilizers, but also key regulators of oleogel architecture and bioactive functionality. These results provide a structure–digestion–bioactivity correlation for protein–polysaccharide oleogels, representing a rational design strategy for high-performance delivery systems of lipid-soluble nutraceuticals. Full article

Hypertension and chronic kidney disease (CKD) are closely linked conditions and represent common global health problems. Hypertension is a leading risk factor for cardiovascular disease, which is the main cause of mortality in CKD. Endothelial injury underlies the etiopathogenesis of both hypertension and CKD. The endothelial glycocalyx (eGC) is a dynamic, negatively charged, carbohydrate-rich layer that covers the luminal surface of endothelial cells. Its primary physiological function is to protect the endothelium, including the regulation of vascular permeability and homeostasis. Damage to the eGC, known as “shedding”, is an early predictor of endothelial dysfunction and is driven by oxidative stress and low-grade inflammation. In hypertension, loss of eGC integrity—often impaired by a high-salt diet—can reduce the bioavailability of nitric oxide (NO) and increase arterial stiffness. Similarly, in CKD, uremic toxicity, hypertension, and inflammation damage the eGC, resulting in increased permeability, albuminuria, and higher cardiovascular risk. This review summarizes current evidence and underscores the potential of eGC shedding markers, especially syndecan 1 (SDC-1) and hyaluronic acid (HA), as early predictors of vascular risk and disease progression in hypertension and CKD. Full article

Phytochemicals have attracted considerable attention as therapeutically relevant bioactive compounds due to their diverse pharmacological activities, including anti-inflammatory, antioxidant, anticancer, and metabolic regulatory effects. However, their clinical translation is frequently hindered by unfavorable pharmaceutical properties such as poor aqueous solubility, chemical instability, rapid metabolism, and limited bioavailability. These challenges have constrained the reproducibility and therapeutic reliability of phytochemical-based interventions. In this context, nanotechnology-enabled delivery systems have emerged as effective strategies to overcome the intrinsic limitations of phytochemicals and enhance their biological performance. This review provides a comprehensive overview of recent advances in nanotechnology-based delivery platforms for phytochemicals, with emphasis on lipid-based nanocarriers, polymeric nanoparticles, nanoemulsions and self-nanoemulsifying drug delivery systems, inorganic and hybrid nanocarriers, as well as hydrogel-based and transdermal delivery systems. We discuss how rational nanocarrier design improves solubility, stability, pharmacokinetics, cellular uptake, and tissue targeting, thereby enhancing therapeutic efficacy across multiple disease areas. In addition, critical safety, toxicity, manufacturing, and regulatory considerations that influence translational potential are addressed. By adopting a delivery-centered perspective, this review highlights current challenges and future opportunities in nano-phytomedicine and underscores the importance of integrating nanotechnology, biological insight, and regulatory-conscious development to advance phytochemicals toward clinically viable therapeutic applications. Full article

Background/Objectives: Allergic conjunctivitis (AC) is the most common inflammatory disease affecting the ocular conjunctiva. Tacrolimus (TCR), a potent calcineurin inhibitor, is limited by poor aqueous solubility and low ocular bioavailability. This study aimed to develop TCR-loaded cubosomes (TCR-Cubs) incorporated into HPMC/PVP K90 dissolving microneedles (MNs) to enhance their therapeutic efficacy. Methods: TCR-Cubs were prepared using a modified top-down fragmentation method with glyceryl monooleate and poloxamer 407, optimized via Box–Behnken design, and incorporated into dissolving MNs. The system was evaluated in vitro, ex vivo, and in vivo using a rabbit model of allergic conjunctivitis. Results: The optimized formulation exhibited the smallest particle size (210 ± 0.91 nm), polydispersity index (0.29 ± 0.03), zeta potential (−21 ± 0.87 mV), and the highest entrapment efficiency (% 93.3 ± 0.45). The optimized formulation was incorporated into MNs via micro molding. Scanning electron microscopy (SEM) confirmed well-defined, sharp microneedles, with low height reduction (<10%) by mechanical testing and high penetration efficiency (>85–90%). In vitro release studies revealed sustained drug release of (~75–80%) over 24 h, compared to (~40%) from the TCR suspension, following diffusion-controlled kinetics. Ex vivo permeation studies showed a (~2–3-fold) enhancement in corneal drug flux. In vivo pharmacodynamic evaluation using an ovalbumin-induced allergic conjunctivitis model demonstrated significant reductions in inflammatory mediators, including inflammatory markers (TNF-α, IL-1β, IL-6, NLRP3), which were reduced by (~50–75%), with modulation of CPA3, BCL2, and TGF-β1 by qRT-PCR. Histopathology and TLR4 analysis confirmed reduced inflammation without irritation. Conclusions: This dual-delivery system offers a promising, non-invasive platform for enhanced ocular delivery of tacrolimus with superior anti-inflammatory efficacy in allergic conjunctivitis. Full article

Cardiovascular disease continues to impose a substantial global health burden and arises from interconnected pathological processes, including oxidative injury, inflammatory signaling, endothelial dysfunction, metabolic imbalance, and progressive cardiac and vascular structural remodeling. Growing interest has therefore emerged in naturally derived compounds capable of influencing multiple disease pathways simultaneously. Pterostilbene, a dimethoxylated stilbene structurally related to resveratrol, has gained attention due to its enhanced lipophilicity and improved bioavailability. Recent experimental studies have investigated the cardiovascular effects of pterostilbene in both cellular systems and animal models. Evidence from in vitro studies indicates that this compound modulates key regulatory networks involved in cellular energy metabolism, redox homeostasis, endothelial signaling, and stress-associated cardiomyocyte injury. These actions involve pathways linked to 5′ adenosine monophosphate-activated protein kinase and sirtuin-1 signaling, nitric oxide regulation, antioxidant responses, and ferroptosis-related mechanisms. Findings from in vivo investigations further demonstrate protective effects across multiple cardiovascular disease models, including pulmonary hypertension, pressure overload-associated cardiac remodeling, ischemic myocardial injury, toxin-induced cardiotoxicity, and metabolic or atherosclerotic vascular dysfunction. Improvements in functional, structural, and biochemical parameters have been reported in these experimental settings. Overall, current preclinical evidence suggests that pterostilbene may act as a multifunctional modulator of key processes involved in cardiovascular pathology. Although clinical evidence remains limited, the convergence of mechanistic and experimental findings highlights its potential as a multi-target cardiometabolic therapeutic candidate and provides a foundation for future translational and clinical investigation. Full article

There is an increasing interest in functional food formulations with added bioactive compounds, such as vitamins, probiotics, polyphenols and bioactive peptides, specifically in dairy and plant-based foods, bakery, and beverages. However, their stability in the food system, release rates and biological activity after consumption/digestion play an important role in the effectiveness of functional foods. There are technical challenges in maintaining the stability and acceptability of added compounds in the formulation design of food items. A novel approach to delivering bioactive compounds in functional foods is their microencapsulation, where stability-sensitive compounds are protected against their degradation during processing and physiological digestion, with targeted release in the gastrointestinal tract (GIT) and elicited cellular responses. Microencapsulation of bioactive compounds has been proven to be beneficial in in vitro models for the stability, antioxidant and immunomodulatory action, and acceptability compared to free (non-capsulated) forms. This technology is worth considering relative to the protection of health benefits of compounds used in food products, with their necessary bioactivity after physiological digestion in GIT. This article reviews important bioactive compounds, challenges, and strategies in the development of functional foods to ensure the required stability for the bioavailability of added compounds. Full article

Ocular fungal diseases are associated with severe infection and pain and, in advanced stages, can lead to vision loss. Current treatment options are limited to the topical application of conventional drugs, and the bioavailability of these drugs is quite limited due to ocular barriers. In this study, a dual-drug nanodelivery system was developed to improve intraocular drug delivery by combining antifungal and anti-inflammatory therapies. Posaconazole (PSC), a broad-spectrum triazole antifungal agent, and dexketoprofen trometamol (DKP), a rapidly acting nonsteroidal anti-inflammatory drug, were co-loaded onto polymeric micelles and then incorporated into electrospun poly(vinyl alcohol)/poly(vinylpyrrolidone) (PVA/PVP) nanofiber intraocular implants. DSC, XRD, FTIR, and FESEM analyses showed that both APIs were successfully converted into nanofiber form without disrupting the micelle structure. Comparative studies with DKP solution and PSC commercial oral suspension (Noxafil^® 40 mg/mL) showed that the produced micelle-loaded nanofibers provided sustained release and significantly increased ex vivo ocular permeation and penetration. In vitro antifungal activity tests demonstrated efficacy against Candida albicans, and HET-CAM toxicity tests showed that the micelle-loaded nanofibers were non-irritating and suitable for ocular application. Overall, the micelle-loaded electrospun nanofiber ocular inserts developed in this study represent a promising platform for combined antifungal and anti-inflammatory ocular therapy. Full article