Search Results (232)

Background/Objectives: Parenteral nutrition (PN) supports patients unable to receive nutrients via the gastrointestinal tract, but it lacks the health-promoting natural bioactive compounds found in a typical oral diet. This study aimed to develop a human serum albumin-based intravenous delivery system for lutein (an antioxidant carotenoid with vision-supportive and hepatoprotective properties) as a PN additive. Methods: An albumin–lutein nanosuspension (AlbLuteN) was synthesized using a modified nanoparticle albumin-bound (nab^TM) technology and characterized physicochemically. The nanoformulation was added to four commercial PN admixtures to assess the supplementation safety throughout the maximum infusion period. Visual inspection and measurements of fat globules larger than 5 µm (PFAT5) and the mean hydrodynamic diameter (Z-average), zeta potential, pH, osmolality, and lutein content were performed to detect potential interactions and evaluate the physicochemical stability. Results: AlbLuteN consisted of uniform particles (Z-average of 133.5 ± 2.8 nm) with a zeta potential of −28.1 ± 1.8 mV, lutein content of 4.76 ± 0.39%, and entrapment efficiency of 84.4 ± 6.3%. Differential scanning calorimetry confirmed the amorphous state of lutein in the nanosuspension. AlbLuteN was successfully incorporated into PN admixtures, without visible phase separation or significant changes in physicochemical parameters. The PFAT5 and Z-average values remained within pharmacopeial limits over 24 h. No substantial shifts in zeta potential, pH, or osmolality were observed. The lutein content remained stable, with losses below 3%. Conclusions: AlbLuteN can be safely added to representative PN admixtures without compromising their stability. This approach offers a novel strategy for intravenous lutein delivery and may contribute to improving the nutritional profile of PN. Full article

Flavonols, representing a subclass of flavonoids, are an important group of polyphenols. Their activity is associated with a number of beneficial properties, including hepatoprotective, senolytic, neuroprotective, and anticancer properties. They are found abundantly in many fruits, vegetables, and plant products, but flavonols’ chemistry and structural properties result in their low bioavailability in vivo. In recent years, more and more studies have emerged that aim to increase the therapeutic potential of compounds belonging to this group, including by developing innovative nanoformulations. The present work focuses on the various steps, such as chemical analysis of the compounds, preformulation studies using drug delivery systems, preclinical studies, and finally clinical trials. Each of these elements is important not only for the innovation and efficacy of the therapy but most importantly for the patient’s health. There are also a limited number of studies assessing the population concentration of flavonols in the blood; therefore, this review presents an up-to-date survey of the most recent developments, using the most important compounds from the flavonol group. Full article

Background/Objectives: Ultraviolet B (UVB) radiation contributes significantly to skin aging and skin disorders by promoting oxidative stress, inflammation, and collagen degradation. Natural antioxidants such as theaflavins and thearubigins from Camellia sinensis L. (black tea) have shown photoprotective effects. This study aimed to optimize the extraction of theaflavins and thearubigins from black tea leaves and evaluate the efficacy of the extract against UVB-induced damage using a transfersome-based topical formulation. Methods: Extraction of theaflavins and thearubigins was optimized via response surface methodology (Box-Behnken Design), yielding an extract rich in active polyphenols. This extract was incorporated into transfersomes that were characterized for size, polydispersity, zeta potential, storage stability, and entrapment efficiency. Human dermal fibroblasts (NHDF) were used to assess cytotoxicity, protection against UVB-induced viability loss, collagen degradation, and expression of inflammatory (IL6, COX2, iNOS) and matrix-degrading (MMP1) markers. Cellular uptake of the extract’s bioactive marker compounds was measured via LC-MS/MS. Results: The transfersomes (~60 nm) showed a good stability and a high entrapment efficiency (>85%). The transfersomes significantly protected NHDF cells from UVB-induced cytotoxicity, restored collagen production, and reduced gene expression of MMP1, IL6, COX2, and iNOS. Cellular uptake of key extract’s polyphenols was markedly enhanced by the nanoformulation compared to the free extract. Conclusions: Black tea extract transfersomes effectively prevented UVB-induced oxidative and inflammatory damage in skin fibroblasts. This delivery system enhanced bioavailability of the extract and cellular protection, supporting the use of the optimized extract in cosmeceutical formulations targeting photoaging and UV-induced skin disorders. Full article

Background/Objectives: Ovarian cancer (OC) remains one of the most lethal malignancies of the female reproductive system. Glucose oxidase (GOx) has emerged as a potential therapeutic agent in cancer treatment by inducing tumor starvation through glucose depletion. Nonetheless, its clinical application is constrained due to its systemic toxicity, immunogenicity, poor in vivo stability, and short half-life. These challenges can be addressed through nanotechnology; in particular, biogenic mesoporous silica nanoparticles (MSNs) offer promise as drug delivery systems (DDSs) that enhance therapeutic efficacy while minimizing side effects. Methods: Biogenic MSNs were extracted from the Equisetum myriochaetum plant via acid digestion, functionalized with 3-aminopropiltrietoxysilane (APTES) and glutaraldehyde (GTA), and loaded with GOx. The free and immobilized MSNs were characterized using FTIR, DLS, XRD, SEM/EDX, and BET techniques. A colorimetric approach was employed to quantify the enzymatic activity of both the free and immobilized GOx. The MTT assay was employed to assess the viability of SKOV3 cells. The obtained IC₅₀ concentration of the nanoformulation was administered to SKOV3 cells to analyze the expression of cancer-related genes using RT-qPCR. Results: IC₅₀ values of 60.77 ng/mL and 111.6 µg/mL were ascertained for the free and immobilized GOx, respectively. Moreover, a significant downregulation of the oncogene β-catenin (CTNNB1) was detected after 24 h with the nanoformulation. Conclusions: Our findings indicate that GOx-loaded biogenic MSNs may serve as a potential therapeutic agent for ovarian cancer. This is, to the best of our knowledge, the first report exploring the effect of GOx-loaded biogenic MSNs on SKOV3 cells. Full article

Background/Objectives: This study aims to present a strategic approach to enhancing the photostability and antioxidative resilience of curcumin and capsaicin by integrating selected natural stabilizers within a nanoemulsion-based delivery system. Methods: Coffee extract (Coffea arabica Linn.), along with its active components and vitamin E-containing natural oils, was assessed in terms of improving the photostabilizing and antioxidative retention abilities of curcumin and capsaicin. An optimized ratio of the active mixture was then loaded into a nanoformulation. Results: The analysis of active contents with validated high-performance liquid chromatography (HPLC), ferric reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays confirmed the stabilization enhancement after irradiation with UV and white light for 72,000–84,000 lux hours. The optimized combination of coffee extract with turmeric and chili mixtures loaded into the optimized nanoemulsion enhanced the half-lives (T_1/2) of curcumin and capsaicin by 416% and 390%, respectively. The interactions of curcumin and capsaicin with caffeine and chlorogenic acid were elucidated using computational calculations. Interaction energies (E_int), HOMO-LUMO energy gap (HLG) analysis, and global reactivity descriptors revealed hydrogen bonding interactions be-tween capsaicin and chlorogenic acid, as well as between curcumin and caffeine. Conclusions: By leveraging the synergistic antioxidative properties of coffee extract and vitamin E within a nanoemulsion matrix, this study overcomes the intrinsic stability limitations of curcumin and capsaicin, offering a robust platform for future pharmaceutical and nutraceutical applications. Full article

Global concerns about environmental pollution, poor waste management, and the rise in antimicrobial resistance due to uncontrolled antibiotic use have driven researchers to seek alternative, multifaceted solutions. Plants, animals, microorganisms, and their processing wastes serve as valuable sources of natural biopolymers and bioactive compounds. Through nanotechnology, these can be assembled into formulations with enhanced antimicrobial properties, high safety, and low toxicity. This review explores polysaccharides, including chitosan, alginate, starch, pectin, cellulose, hemicellulose, gums, carrageenan, dextran, pullulan, and hyaluronic acid, used in nanotechnology, highlighting their advantages and limitations as nanocarriers. Addressing the global urgency for alternative antimicrobials, we examined natural compounds derived from plants, microorganisms, and animals, such as phytochemicals, bacteriocins, animal antimicrobial peptides, and proteins. Focusing on their protection and retained activity, this review discusses polysaccharide-based nanoformulations with natural antimicrobials, including nanoparticles, nanoemulsions, nanocapsules, nanoplexes, and nanogels. Special emphasis is placed on strategies and formulations for the encapsulation, entrapment, and conjugation of natural compounds using polysaccharides as protective carriers and delivery systems, including a brief discussion on their future applications, prospects, and challenges in scaling up. Full article

Chronic wounds, including diabetic foot ulcers and pressure sores, are becoming more prevalent due to aging populations and increased metabolic problems. These wounds often persist due to impaired healing, chronic inflammation, oxidative stress, and infections caused by multidrug-resistant pathogens, making conventional treatments—including antibiotics and antiseptics—largely inadequate. This creates an urgent need for advanced, biologically responsive therapies that can both combat infection and promote tissue regeneration. Probiotics have surfaced as a viable option owing to their capacity to regulate immune responses, impede pathogenic biofilms, and generate antibacterial and antioxidant metabolites. However, their clinical application is limited by poor viability, sensitivity to environmental conditions, and short retention at wound sites. Nanotechnology-based delivery systems address these limitations by protecting probiotics from degradation, enhancing site-specific delivery, and enabling controlled, stimuli-responsive release. Encapsulation techniques using materials like chitosan, PLGA, liposomes, nanogels, nanofibers, and microneedles have shown significant success in improving wound healing outcomes in preclinical and clinical models. This review summarizes the current landscape of chronic wound challenges and presents recent advances in probiotic-loaded nanotechnologies. It explores various nano-delivery systems, their mechanisms of action, biological effects, and therapeutic outcomes, highlighting the synergy between probiotics and nanocarriers as a novel, multifaceted strategy for managing chronic wounds. Full article

The mRNA vaccine has protected humans from the Coronavirus disease 2019 (COVID-19) and has taken the lead in reversing the epidemic efficiently. However, the Centre of Disease Control (CDC) reported and raised the alarm of allergic or acute inflammatory adverse reactions after vaccination with mRNA-LNP vaccines. Meanwhile, the US Food and Drug Administration (FDA) has added four black-box warnings in the instructions for mRNA-LNP vaccines. Numerous studies have proven that the observance of side effects after vaccination is indeed positively correlated to the level of anti-PEG antibodies (IgM or IgG), which are enhanced by PEGylated preparations like LNP vaccine and environmental exposure. After literature research and review in the past two decades, it was found that the many clinical trial failures (BIND-014, RB006 fell in phase II) of PEG modified delivery system or PEGylated drug were related to the high expression of anti-PEG IgM and IgG. In the background of shooting multiple mRNA-LNP vaccines in billions of people around the world in the past three years, the level of anti-PEG antibodies in the population may have significantly increased, which brings potential risks for PEG-modified drug development and clinical safety. This review summarizes the experience of using mRNA-LNP vaccines from the mechanism of the anti-PEG antibodies generation, detection methods, clinical failure cases of PEG-containing products, harm analysis of abuse of PEGylation, and alternatives. In light of the increasing prevalence of anti-PEG antibodies in the population and the need to avoid secondary injuries, this review article holds greater significance by offering insights for drug developers. It suggests avoiding the use of PEG excipients when designing PEGylated drugs or PEG-modified nano-formulations and provides references for strategies such as utilizing PEG-free or alternative excipients. Full article

Autoimmune diseases are driven by chronic inflammation and oxidative stress, thus requiring innovative therapeutic approaches. Polymeric nanotherapeutics incorporating antioxidant bioactive compounds offer a promising strategy for immune modulation and enhanced drug delivery. This review explores the application of polymer-based nanocarriers for improving the solubility, bioavailability, and targeted delivery of antioxidant compounds in autoimmune disease treatment. A comprehensive analysis of recent advancements in polymeric nanoformulations, including poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), chitosan, and hyaluronic acid, was conducted. The therapeutic efficacy of various antioxidant-loaded nanoparticles has been assessed in both preclinical and clinical studies. Phenolic antioxidants, such as resveratrol, curcumin, quercetin, and epigallocatechin-3-gallate, exhibit potent anti-inflammatory effects; however, their poor solubility limits their clinical application. Nanocarriers such as dendrosomes, tannic acid-based reactive oxygen species (ROS)-scavenging nanoparticles, and folic acid-functionalized systems enhance drug stability, controlled drug release, and macrophage targeting. Carotenoid and bilirubin nanoparticles further demonstrate immunomodulatory effects in multiple sclerosis, psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Polymeric antioxidant nanotherapeutics provide targeted and sustained drug delivery, offering improved efficacy and reduced toxicity. Future research should focus on optimizing these nanocarriers for clinical translation and patient-centered therapeutic strategies. Full article

Isorhamnetin (ISO) is a natural flavonoid compound that has become a main research topic in recent years due to its multitargeted antitumor properties. In this paper, we systematically review the molecular basis of the inhibition of malignant tumors by ISO, including through the regulation of the cell cycle, PI3K/AKT/mTOR pathway, MAPK pathway, apoptosis/autophagy-related pathways, and the tumor microenvironment. We also explore its synergistic effects with chemotherapy/targeted therapies and its potential for clinical translation. Experimental studies have shown that ISO can not only directly inhibit tumor proliferation by inducing tumor cell cycle arrest, mitochondria-dependent apoptosis, and endoplasmic reticulum stress, but also enhance antitumor immune responses by regulating the immune microenvironment. Pharmacokinetic studies have shown that novel delivery systems, such as nano-formulations, significantly enhance the bioavailability of ISO. Notably, ISO has demonstrated unique advantages in attenuating the nephrotoxicity of chemotherapeutic agents, protecting normal cells, and reversing tumor resistance. However, the optimal dosing regimen, dose–effect relationship, and cross-species applicability need to be further validated by large-scale preclinical animal experiments and clinical trials. This paper provides a theoretical basis for the development and application of ISO for the treatment of malignant tumors and highlights its potential value in animal models. Full article

Periodontitis is a prevalent oral condition worldwide. Azithromycin, a conventional lipophilic drug for periodontal treatment, often causes systemic side effects when administered orally. To address this, azithromycin-loaded nano-emulgels were developed using olive oil as a carrier within a xanthan gum aqueous gel phase. This oil-in-aqueous gel emulsion was actuated into a foam for localized drug delivery in gingival and periodontal disease. The solubility of azithromycin in various vehicles was tested, with olive oil showing the best solubility (0.347 mg/mL). Thermodynamic stability testing identified viable nano-formulations, with encapsulation efficiencies ranging from 98 to 100%. These formulations exhibited rapid drug release within 2–8 h. Muco-adhesion studies and ex vivo permeability tests on porcine buccal mucosa highlighted the beneficial properties of xanthan gum for local drug retention within the oral cavity. Antimicrobial efficiency was assessed using minimum inhibitory concentrations against various oral pathogens, where the formulation with equal surfactant and co-surfactant ratios showed the most potent antibacterial activity, ranging from 0.390 to 1.56 µg/mL. This was supported by the shear-thinning, muco-adhesive, and drug-retentive properties of the xanthan gel base. The study also examined the influence of the oil phase with xanthan gum gel on foam texture, rheology, and stability, demonstrating a promising prototype for periodontitis treatment. Full article

Wounds are broadly classified into acute and chronic types, with chronic wounds being those that cannot heal within 4 to 12 weeks despite treatment. There is a growing interest in efficient and cost-effective wound healing though the drug delivery of active molecules. Natural compounds such as phytochemicals, as well as synthetic molecules with antimicrobial or anti-inflammatory growth factors, can impact tissue regeneration and prevent wound infections. Nanotechnology-based systems, such as polymeric and inorganic nanoparticles and electrospun nanofibrous matrices loaded with phytochemicals, can enhance the therapeutic efficacy of active molecules through improved bioavailability and targeted delivery. This review summarizes the most current advanced applications combining phytochemicals and nanoformulations with promising wound healing potential. Various nanosystems loaded with phytochemicals have been identified, such as silver nanocarriers, zein-based nanoparticles, and various known polymers, which can be utilized to develop electrospun fibrous structures loaded with phytoremedies. Despite the incorporation of these remedies into traditional medicine for a long time, further clinical studies are essential to determine their pharmacological properties, safety concerns, and therapeutic efficacy. Full article

Background/Objectives: Natural products are gaining increasing importance due to the large variety of biological activities exerted by their constituents. Among these, the products deriving from Acmella oleracea (L.) R.K. Jansen can be exploited for their local anaesthetic, myorelaxant, anti-inflammatory/analgesic, and antifungal properties. In this regard, there is a need to develop novel formulations for the topical delivery of A. oleracea-derived extracts to widen their use in the pharmaceutical and cosmetic fields. Methods: Nanoformulations, i.e., nanoemulsions (NEs) and microemulsions (MEs), were investigated as a strategy to encapsulate an extract from A. oleracea at the nanoscale level in water and then incorporated into xanthan gum-based hydrogels. Results: Only NEs provided a physically stable formulation, while the precipitation of solid hydrophobic components from the extract was observed during ME preparation under all tested conditions despite the use of ethyl oleate as an oily co-solvent. The optimized NE-based hydrogel remained physically stable over six months, as confirmed by rheological measurements and polarized optical microscope observation, without a phase separation phenomenon. Therefore, NEs resulted more suitable nanodispersed systems than MEs for the encapsulation of A. oleracea extract, which contains a large amount of hydrophobic constituents that are solid at room temperature. Furthermore, the sustained spilanthol release across an artificial membrane (Franz cell apparatus) and the cytotoxic profile on HaCaT cell line support its potential topical application. Conclusions: The outcomes of this study provided valuable insights into the formulation of A. oleracea extract, broadening its fields of applicability, including topical administration. Full article

Croton cajucara Benth and Copaifera reticulata Ducke are prominent species in the traditional medicine of the Amazon region of Brazil. Copaifera species produce oil resin rich in bioactive diterpenes, and C. cajucara is a prolific producer of the diterpene 19-nor-clerodane trans-dehydrocrotonin (t-DCTN). This research aimed to develop a self-nanoemulsion drug delivery system (SNEDDS) by using copaiba oil resin (C. reticulata) as a carrier for t-DCTN. A stable SNEDDS single-phase nanoemulsion comprising Tween 80 (7%, w/w) and copaiba oil (0.5%, w/w) afforded a fine oil-in-water carrier system (SNEDDS-CO). The dropwise solubilization of t-DCTN (1 mg) into SNEDDS-CO resulted in the nanoformulation called SNEDDS-CO-DCTN. Transmission electron microscopy (TEM) analysis revealed spherical nanodevices, while particle size, polydispersity index (PDI), and zeta potential measurements indicated small nanodroplets (about 10 nm), uniformly distributed (between 0.1 and 0.2) and negatively charged for both systems. The in vitro kinetic of t-DCTN-loaded (SNEDDS-CO-DCTN) analyzed by using simulated conditions of the gastrointestinal microenvironment, as perspective for oral drug delivery, showed a controlled release profile, and corresponded to the Fickian diffusion model. The in vitro antioxidant activity of the samples (t-DCTN, SNEDDS-CO, and SNEDDS-CO-DCTN) was confirmed through total antioxidant capacity (TAC), reducing power, copper ion chelation, and hydroxyl radical scavenging assays. The antioxidant activity of SNEDDS-CO-DCTN which contained 1 mg of t-DCTN per mL⁻¹ of the carrier SNEDDS-CO was similar or even better when compared to the unload t-DCTN solubilized in DMSO (10 mg mL⁻¹). The SNEDDS formulations herein described were successfully obtained under moderated and controlled conditions, exhibiting effective physicochemical data and release characteristics with huge bioaccessibility for co-loading copaiba oil and t-DCTN. The novel colloidal system SNEDDS-CO-DCTN is a potential antioxidant nanoproduct and, from now on, is available for further pharmacological investigations. Full article

The development of advanced high-capacity nanoparticle-based drug loading, precise targeting, low toxicity, and excellent biocompatibility is critical for improving cancer therapeutics. Withaferin A, a natural steroidal lactone derived from Physalis minima, exhibits potential biological activity and holds promise as a therapeutic agent. In this study, a novel nanoconjugate (NC) was developed using gold nanoparticles (AuNPs) functionalized with polyvinylpyrrolidone (PVP), Withaferin A drug, and folic acid for targeted drug delivery in cancer treatment. The AuNPs–PVP–Withaferin A–FA nanoconjugate was synthesized through a layer-by-layer assembly process and was confirmed using UV–visible and FTIR spectroscopy. The hydrodynamic radius, surface charge, and morphology of the NC were characterized using dynamic light scattering (DLS), zeta potential analysis, and electron microscopy, respectively. The nanoformulation demonstrated a pH-responsive drug release, with 92% of Withaferin A released at pH 5, mimicking the tumor microenvironment. In vitro cytotoxicity studies conducted on MCF-7 cells using MTT assays, dual dye staining, and protein expression analysis revealed that the nanoconjugate effectively induced apoptosis in cancer cells. These outcomes emphasize the prospect AuNPs–PVP–Withaferin A–FA nanoconjugate as a targeted and efficient Withaferin A delivery system for cancer therapy, leveraging the inherent anticancer properties of Withaferin A. Full article