Recent Research Progress on the Chemical Constituents, Pharmacology, and Pharmacokinetics of Alpinae oxyphyllae Fructus.

Alpinae oxyphyllae fructus (AOF), the dried mature fruit of Alpinia oxyphylla Miquel of the Zingiberaceae family, shows many special pharmacological effects. In recent years, there has been an abundance of research results on AOF. In this paper, the new compounds isolated from AOF since 2018 are reviewed, including terpenes, flavonoids, diarylheptanoids, phenolic acid, sterols, alkanes, fats, etc. The isolation methods that were applied include the microwave-assisted method, response surface method, chiral high-performance liquid chromatography-multiple reaction monitoring-mass spectrometry (HPLC-MRM-MS) analytical method, ultra-high-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry (UPLC-Orbitrap-HRMS) method, ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method, hot water leaching method, ethanol leaching method, and so on. Additionally, the pharmacological effects of AOF found from 2018 to 2024 are also summarized, including neuroprotection, regulation of metabolic disorders, antioxidant activity, antiapoptosis, antiinflammatory activity, antidiabetic activity, antihyperuricemia, antiaging, antidiuresis, immune regulation, anti-tumor activity, renal protection, hepatoprotection, and anti-asthma. This paper provides a reference for further research on AOF.

Idebenone-Loaded Nanocomposite Microspheres for Nasal Administration-A Perspective in the Treatment of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease results in neurodegeneration and is characterized by an accumulation of abnormal neuritic lesions and intracellular aggregates of hyperphosphorylated Tau proteins in the cerebrum. That leads to progressive decline in memory, thinking, and learning skills. Oxidative stress has been shown to play a significant role in the pathogenesis of Alzheimer's disease. Antioxidants are identified as part of therapeutic strategy to prevent or reduce the disease. Idebenone is a synthetic analogue of coenzyme Q10 with potent antioxidant properties, originally developed for the treatment of Alzheimer's disease and other cognitive disorders. After oral administration idebenone undergoes excessive first-pass metabolism and has a very low bioavailability of only about 1%. The use of an alternative route of administration such as the nasal and its incorporation into a novel carrier (nanocomposite microspheres) will eliminate the problems associated with reduced absorption, stability, and rapid biotransformation and will increase the opportunity for idebenone to realize its therapeutic potential in Alzheimer's disease. METHODS: Idebenone-loaded nanocomposite microspheres were obtained by spray drying. The structures were characterized using laser diffraction, scanning electron microscopy, high-performance liquid chromatography, Fourier-transform infrared spectroscopy, and differential scanning calorimetry. The ability of nanocomposite microspheres to bind human serum albumin was investigated by fluorescence spectroscopy. The mucoadhesive properties of the carrier were also determined. RESULTS: Bioadhesive nanocomposite microparticles with spherical shape, smooth surface, size of 7.37 ± 2.4 µm, and with high production yield, good drug entrapment efficiency, and loading values were obtained. Infrared spectra demonstrated no chemical interactions between idebenone and structure-forming polymers. The ability of particles to bind to human serum albumin depends on their drug loading. CONCLUSIONS: Nanocomposite microspheres were developed as the novel delivery system of idebenone for target nose-to-brain delivery. The obtained carrier may increase the therapeutic potential of idebenone by providing higher concentrations in brain tissue and reducing systemic exposure and side effects.

Bioaccessibility of condensed tannins and their effect on the physico-chemical characteristics of lamb meat.

The bioaccessibility of tannins as antioxidants in meat is essential to maximise their effectiveness in protecting the product. This property determines the amount of tannins available to interact with meat components, inhibiting lipid and protein oxidation and, consequently, prolonging shelf life and preserving the sensory quality of the product. The objective of this study was to evaluate the bioaccessibility of condensed tannins (CT) from Acacia mearnsii extract (AME) and their effect on the physico-chemical characteristics of fattened lamb meat. Thirty-six Dorset × Hampshire lambs (3 months old and 20.8 ± 3.3 kg live weight) were used. The lambs were distributed equally (n = 9) into four treatments: T1, T2, T3 and T4, which included a basal diet plus 0%, 0.25%, 0.5% and 0.75% of CT from AME, respectively. At the end of the fattening period, bioaccessibility was evaluated, the animals were slaughtered and a sample of the longissimus dorsi (LD) muscle was collected to assess colour, lipid oxidation, cooking weight loss and shear force on days 1, 4, 7 and 14 of shelf-life, in samples preserved at -20 °C. In addition, the long chain fatty acid profile was analysed. A completely randomised design was used, and the means were compared with Tukey's test (P < 0.05). The mean lightness (L*), yellowness (b*) and hue (H*) values were higher for T3 and T4. The addition of CT did not affect (P > 0.05) redness (a*), cooking weight loss (CWL) or shear force (SF). T4 decreased (P < 0.05) stearic acid and increased cis-9 trans-12 conjugated linoleic acid (CLA). Bioaccessibility was higher in the supplemented groups (T1 < T2, T3 and T4). In conclusion, supplementing CT from AME in the diet of lambs did not reduce lipid oxidation, but T3 or T4 improved some aspects of meat colour and CLA deposition.

Pulmonary delivery of magnolol-loaded nanostructured lipid carriers for COPD treatment.

Chronic obstructive pulmonary disease (COPD) is a prevalent lung condition characterized by airflow obstruction, disability, and high mortality rates. Magnolol (MA), known for its anti-inflammatory and antioxidant properties, holds the potential for alleviating COPD symptoms. However, MA faces challenges like poor aqueous solubility and low bioavailability. Herein MA-loaded nanostructured lipid carriers (MA-NLC) were prepared using emulsification and solvent evaporation. These carriers exhibited a particle size of (19.67 ± 0.36) nm, a polydispersity index of (0.21 ± 0.01), and a zeta potential of (-5.18 ± 0.69) mV. The fine particle fraction of MA-NLC was (68.90 ± 0.07)%, indicating minimal lung irritation and enhanced safety. Pulmonary delivery of MA-NLC via nebulizer actively targeted the diseased lung tissues, facilitated slow release, and overcame the challenges of low oral absorption and bioavailability associated with MA. This formulation prolonged the residence time of MA and optimized its therapeutic effect in pulmonary tissues. Upon pulmonary administration, MA-NLC effectively regulated inflammatory and oxidative stress markers in COPD models, demonstrating its potential as a promising therapeutic platform for COPD management.

Potential bioaccessibility and bioavailability of polyphenols and functional properties of tiger nut beverage and its by-product during in vitro digestion.

"Horchata de chufa" is a beverage produced from tiger nut tubers, which yields a high amount of by-product. This study explored the functional properties of the Spanish tiger nut beverage (TNB) and its by-product (TNBP) together with the bioaccessibility and bioavailability of polyphenols in vitro. TNB and TNBP were characterized for polyphenols via LC/MS/MS and underwent in vitro digestion (INFOGEST). The total antioxidant capacity (TAC) of all bioaccessible fractions and digestion residues was assessed. Intestinal bioaccessible fractions were tested for the ability to inhibit the activity of digestive enzymes (α-amylase, α-glucosidase, and lipase) and the content of polyphenols, whose bioavailability was assessed in a Caco-2 cell model. Thirteen polyphenols were quantified and found to be more abundant in TNB (603 ± 1.4 µg g-1 DW) than in TNBP (187 ± 1.0 µg g-1 DW). Polyphenol bioaccessibility was higher for TNBP than that for TNB (57% vs. 27%), and despite a similar TAC of the intestinal bioaccessible fractions (10.2 ± 0.1 µmoL vs. 9.2 ± 0.03 µmoL eq. Trolox per g DW for TNB and TNBP, respectively), the different patterns of polyphenols released upon digestion suggested the higher ability of TNBP fraction to inhibit α-glucosidase and lipase. TNBP digestion residue showed higher TAC than TNB. Moreover, TNB polyphenols exhibited over 80% bioavailability, whereas TNBP polyphenols' bioavailability ranged from 62% to 84%. Overall, the findings demonstrated that TNBP maintains a high nutritional value, thus suggesting its possible reuse in innovative, healthy, and sustainable foods.

Hydroxytyrosol permeability comparisons and strategies to improve hydroxytyrosol stability in formulations.

There has been a growing interest in hydroxytyrosol (HT) due to its powerful antioxidant and free-radical scavenging properties when added to formulations such as pharmaceuticals and cosmetics. To study the stability and transdermal properties of hydrogels and creams (HT-based formulations), a high-performance liquid chromatography method was developed for determining HT. In the Franz diffusion cell system, both hydrogel and cream show a rapid and similar penetration profile through the Bama miniature pig skin. However, the Strat-M® membrane exhibits slightly lower permeability and is selective to different formulations; that is, the cream has a permeability value of 10.69%, while the hydrogel has a value of 5.27%. The dynamics parameters from the permeation assays indicate that the model using the Strat-M® membrane can be used as a screening tool to evaluate the skin uptake and permeation efficacy of different formulations. Adding 3-O-ethyl-L-ascorbic acid to HT-based formulations can effectively prevent discoloration under prolonged high-temperature storage, while combining multiple antioxidants delays degradation most effectively. This study provides novel ideas for functional formulation optimization to enhance the realism and reproducibility of cosmetic products containing HT and provides scientific evidence for the production, packaging, shelf life, storage, and transportation of products.

QbD-based formulation development of resveratrol nanocrystal incorporated into soluble mesoporous material: Pharmacokinetic proof of concept study.

Resveratrol (RSV) has powerful antioxidant activities. However, the bioavailability is still limited due to low solubility and transport issues. Nanocrystal technology has been introduced to address these issues; however, the bulky formulation of the nanocrystal process through nanosuspension faces a big challenge in terms of stability and scale-up ability. This work aimed to enhance the bioavailability of RSV through nanocrystal formulation incorporated into soluble mesoporous carriers for superior solid-state stability and feasibility. This formulation was designed and developed rationally through scientific justification in the nanocrystal formulation along with quality by design paradigm. Box-Behnken design was applied to determine the optimized formulation based on the particle size and distribution, drug loading, zeta potential, and supersaturation parameters. The nanocrystal was formed through evaporation of drug, polymer, and surfactant in the solvent incorporated into mesoporous material. The nanocrystal was evaluated by vibrational spectroscopy, thermal analyses, and SEM and TEM photographs, followed by crystallinity evaluation. The results indicated that the factors only affected the particle size variation, zeta potential, drug loading, and the time to reach the supersaturation peak level. The optimized formulation was achieved by 68 % desirability value, producing 133.3 ± 1.2 nm particle size and -24.6 mV zeta potential. The physical and chemical evaluation characterization indicated no interaction between RSV and carrier. In addition, there was no difference in crystallinity between the RSV nanocrystal and native RSV. Moreover, the RSV nanocrystal improved the bioavailability nearly twice compared to the RSV suspension.

A New Tailored Nanodroplet Carrier of Astaxanthin Can Improve Its Pharmacokinetic Profile and Antioxidant and Anti-Inflammatory Efficacies.

Astaxanthin (ATX) is a carotenoid nutraceutical with poor bioavailability due to its high lipophilicity. We tested a new tailored nanodroplet capable of solubilizing ATX in an oil-in-water micro-environment (LDS-ATX) for its capacity to improve the ATX pharmacokinetic profile and therapeutic efficacy. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to profile the pharmacokinetics of ATX and LDS-ATX, superoxide mutase (SOD) activity to determine their antioxidant capacity, protein carbonylation and lipid peroxidation to compare their basal and lipopolysaccharide (LPS)-induced oxidative damage, and ELISA-based detection of IL-2 and IFN-γ to determine their anti-inflammatory capacity. ATX and LDS-ATX corrected only LPS-induced SOD inhibition and oxidative damage. SOD activity was restored only by LDS-ATX in the liver and brain and by both ATX and LDS-ATX in muscle. While in the liver and muscle, LDS-ATX attenuated oxidative damage to proteins and lipids better than ATX; only oxidative damage to lipids was preferably corrected by LDS-ATX in the brain. IL-2 and IFN-γ pro-inflammatory response was corrected by LDS-ATX and not ATX in the liver and brain, but in muscle, the IL-2 response was not corrected and the IFN-γ response was mitigated by both. These results strongly suggest an organ-dependent improvement of ATX bioavailability and efficacy by the LDS-ATX nanoformulation.

Polyphenols: Chemistry, bioavailability, bioactivity, nutritional aspects and human health benefits: A review.

Polyphenols, including phenolics, alkaloids, and terpenes, are secondary metabolites that are commonly found in fruits, vegetables, and beverages, such as tea, coffee, wine, chocolate, and beer. These compounds have gained considerable attention and market demand because of their potential health benefits. However, their application is limited due to their low absorption rates and reduced tissue distribution efficiency. Engineering polyphenol-protein complexes or conjugates can enhance the antioxidant properties, bioavailability, and stability of polyphenols and improve digestive enzyme hydrolysis, target-specific delivery, and overall biological functions. Complex polyphenols, such as melanin, tannins, and ellagitannins, can promote gut microbiota balance, bolster antioxidant defense, and improve overall human health. Despite these benefits, the safety of polyphenol complexes must be thoroughly evaluated before their use as functional food additives or supplements. This review provides a detailed overview of the types of macromolecular polyphenols, their chemical composition, and their role in food enrichment. The mechanisms by which complex polyphenols act as antioxidative, anti-inflammatory, and anticancer agents have also been discussed.

Comparing the antioxidation and bioavailability of polysaccharides from extruded and unextruded Baijiu vinasses via in vitro digestion and fecal fermentation.

Extrusion has been proven to be a novel approach for modifying the physicochemical characteristic of Baijiu vinasses (BV) to extract polysaccharides, contributing to the sustainable development of brewing industry. However, the comparison of the bioactivity and bioavailability of extruded (EX) and unextruded (UE) BV polysaccharides was unclear, which impended the determination of the efficacy of extrusion in BV resourcing. In this study, in vitro digestion and fecal fermentation experiments were conducted to investigate the bioavailability, and the results showed that EX exhibited less variation in the monosaccharide composition and molecular weight, while exhibiting a stronger antioxidant capacity compared to UE. Moreover, during fermentation EX increased the abundance of Parasutterella and Lachnospiraceae, while UE promoted the proliferation of Bacteroides, Faecalibacterium, and Dialister, resulting in variation in short-chain fatty acids. These findings indicate that extrusion can enhance the capacity of antioxidants and bioavailability of BV polysaccharides.

Safety and Pharmacokinetics of a Combined Antioxidant Therapy against Myocardial Reperfusion Injury: A Phase 1 Randomized Clinical Trial in Healthy Humans.

Myocardial reperfusion injury (MRI) accounts for up to 50% of the final size in acute myocardial infarction and other conditions associated with ischemia-reperfusion. Currently, there is still no therapy to prevent MRI, but it is well known that oxidative stress has a key role in its mechanism. We previously reduced MRI in rats through a combined antioxidant therapy (CAT) of ascorbic acid, N-acetylcysteine, and deferoxamine. This study determines the safety and pharmacokinetics of CAT in a Phase I clinical trial. Healthy subjects (n = 18) were randomized 2:1 to CAT or placebo (NaCl 0.9% i.v.). Two different doses/infusion rates of CATs were tested in a single 90-minute intravenous infusion. Blood samples were collected at specific times for 180 minutes to measure plasma drug concentrations (ascorbic acid, N-acetylcysteine, and deferoxamine) and oxidative stress biomarkers. Adverse events were registered during infusion and followed for 30 days. Both CAT1 and CAT2 significantly increased the CAT drug concentrations compared to placebo (P < .05). Most of the pharmacokinetic parameters were similar between CAT1 and CAT2. In total, 6 adverse events were reported, all nonserious and observed in CAT1. The ferric-reducing ability of plasma (an antioxidant biomarker) increased in both CAT groups compared to placebo (P < .001). The CAT is safe in humans and a potential treatment for patients with acute myocardial infarction undergoing reperfusion therapy.

Controlled Quercetin Release by Fluorescent Mesoporous Nanocarriers for Effective Anti-Adipogenesis.

Introduction: Quercetin (QUER), a flavonoid abundant in fruits and vegetables, is emerging as a promising alternative therapeutic agent for obesity treatment due to its antioxidant and anti-adipogenic properties. However, the clinical application of QUER is limited by its poor solubility, low bioavailability, and potential toxicity at high doses. To address these challenges, this study aims to develop an advanced drug delivery system using fluorescent mesoporous silica nanoparticles (FMSNs) coated with polydopamine (PDA) for the efficient and sustained delivery of QUER to inhibit adipogenesis. Methods: The research included the synthesis of PDA-coated FMSNs for encapsulation of QUER, characterization of their mesoporous structures, and systematic investigation of the release behavior of QUER. The DPPH assay was used to evaluate the sustained radical scavenging potential. Concentration-dependent effects on 3T3-L1 cell proliferation, cellular uptake and adipogenesis inhibition were investigated. Results: PDA-coated FMSNs exhibited well-aligned mesoporous structures. The DPPH assay confirmed the sustained radical scavenging potential, with FMSNs-QUER@PDA showing 53.92 ± 3.48% inhibition at 72 h, which was higher than FMSNs-QUER (44.66 ± 0.57%) and free QUER (43.37 ± 5.04%). Concentration-dependent effects on 3T3-L1 cells highlighted the enhanced efficacy of PDA-coated FMSNs for cellular uptake, with a 1.5-fold increase compared to uncoated FMSNs. Adipogenesis inhibition was also improved, with relative lipid accumulation of 44.6 ± 4.6%, 37.3 ± 4.6%, and 36.5 ± 7.3% at 2.5, 5, and 10 µM QUER concentrations, respectively. Conclusion: The study successfully developed a tailored drug delivery system, emphasizing sustained QUER release and enhanced therapeutic effects. FMSNs, especially when coated with PDA, exhibit promising properties for efficient QUER delivery, providing a comprehensive approach that integrates advanced drug delivery technology and therapeutic efficacy.

Whey Protein Sodium-Caseinate as a Deliverable Vector for EGCG: In Vitro Optimization of Its Bioaccessibility, Bioavailability, and Bioactivity Mode of Actions.

Epigallocatechin gallate (EGCG), the principal catechin in green tea, exhibits diverse therapeutic properties. However, its clinical efficacy is hindered by poor stability and low bioavailability. This study investigated solid particle-in-oil-in-water (S/O/W) emulsions stabilized by whey protein isolate (WPI) and sodium caseinate (NaCas) as carriers to enhance the bioavailability and intestinal absorption of EGCG. Molecular docking revealed binding interactions between EGCG and these macromolecules. The WPI- and NaCas-stabilized emulsions exhibited high encapsulation efficiencies (>80%) and significantly enhanced the bioaccessibility of EGCG by 64% compared to free EGCG after simulated gastrointestinal digestion. Notably, the NaCas emulsion facilitated higher intestinal permeability of EGCG across Caco-2 monolayers, attributed to the strong intermolecular interactions between caseins and EGCG. Furthermore, the emulsions protected Caco-2 cells against oxidative stress by suppressing intracellular reactive oxygen species generation. These findings demonstrate the potential of WPI- and NaCas-stabilized emulsions as effective delivery systems to improve the bioavailability, stability, and bioactivity of polyphenols like EGCG, enabling their applications in functional foods and nutraceuticals.

Development and characterization of ferulic acid-loaded chitosan nanoparticle embedded- hydrogel for diabetic wound delivery.

Diabetic wounds present a significant global health challenge exacerbated by chronic hyperglycemia-induced oxidative stress, impeding the natural healing process. Despite various treatment strategies, diabetic foot ulceration lacks standardized therapy. Ferulic acid (FA), known for its potent antidiabetic and antioxidant properties, holds promise for diabetic wound management. However, oral administration of FA faces limitations due to rapid oxidation, stability issues, and low bioavailability. The topical application of FA-loaded chitosan nanoparticles (FA-CSNPs) has emerged as a promising approach to overcome these challenges. Here, we report the development of a sustained-release formulation of FA-CSNPs within a hydrogel matrix composed of Chitosan and gelatin. The FA-CSNPs were synthesized using the ionic gelation method andoptimized through a Central Composite Design (CCD) approach. Characterization of the optimized nanoparticles revealed spherical morphology, a particle size of 56.9 ± 2.5 nm, and an impressive entrapment efficiency of 90.3 ± 2.4 %. Subsequently, an FA-CSNPs-loaded hydrogel was formulated, incorporating chitosan as a gelling agent, gelatin to enhance mechanical properties and cell permeation, and glutaraldehyde as a cross-linker. Comprehensive characterization of the hydrogel included pH, moisture loss, porosity, swelling index, rheology, water vapor transmission rate (WVTR), SEM, TEM, invitro drug release studies, antioxidant activity, antibacterial efficacy, cell cytotoxicity, cell migration studies on L929 fibroblast cell line, and stability studies. The stability study demonstrated negligible variations in particle size, zeta potential, and entrapment efficiency over 60 days, ensuring the stable nature of nanoparticles and hydrogel. This innovative delivery approach embedded within a hydrogel matrix holds significant promise for enhancing the therapeutic efficacy of FA-CSNPs-hydrogel in diabetic wound healing applications.

Hyaluronic acid-poly(glyceryl)10-stearate nanoemulsion for co-delivery of fish oil and resveratrol: Enhancing bioaccessibility and antioxidant potency.

Hyaluronic acid (HA), an endogenous polysaccharide comprising alternating D-glucuronic acid and N-acetylglucosamine units, is renowned for its high hydrophilicity, biocompatibility, and biodegradability. These attributes have rendered HA invaluable across medical and drug delivery fields. HA can be altered through physical, chemical, or enzymatic methods to improve the properties of the modified substances. In this work, we synthesized a derivative via the esterification of HA with poly(glyceryl)10-stearate (PG10-C18), designated as HA-PG10-C18. This novel derivative was employed to fabricate a nano co-delivery system (HA-PG10-C18@Res-NE) for fish oil and resveratrol (Res), aiming to enhance their stability and bioaccessibility. An exhaustive investigation of HA-PG10-C18@Res-NE revealed that the HA-modified system displayed superior physicochemical stability, notably in withstanding oxidation and neutralizing free radicals. Moreover, in vitro simulated digestion underscored the system's enhanced bioaccessibility of Res and more efficient release of free fatty acids. These outcomes underscore the strategic advantage of HA in modifying PG10-C18 for nanoemulsion formulation. Consequently, HA-PG10-C18 stands as a promising emulsifier for encapsulating lipophilic bioactives in functional foods, nutraceuticals, and pharmaceuticals.

Review on the pharmacological effects and pharmacokinetics of scutellarein.

Scutellarein is a flavonoid from Scutellaria baicalensis Georgi that has been shown to have a variety of pharmacological activities. This review aims to summarize the pharmacological and pharmacokinetic studies on scutellarein and provide useful information for relevant scholars. Pharmacological studies indicate that scutellarein possesses a diverse range of pharmacological properties, including but not limited to anti-inflammatory, antioxidant, antiviral, neuroprotective, hypoglycemic, hypolipidemic, anticancer, and cardiovascular protective effects. Further investigation reveals that the pharmacological effects of scutellarein are driven by multiple mechanisms. These mechanisms encompass the scavenging of free radicals, inhibition of the activation of inflammatory signaling pathways and expression of inflammatory mediators, inhibition of the activity of crucial viral proteins, suppression of gluconeogenesis, amelioration of insulin resistance, improvement of cerebral ischemia-reperfusion injury, induction of apoptosis in cancer cells, and prevention of myocardial hypertrophy, among others. In summary, these pharmacological studies suggest that scutellarein holds promise for the treatment of various diseases. It is imperative to conduct clinical studies to further elucidate the therapeutic effects of scutellarein. However, it is worth noting that studies on the pharmacokinetics reveal an inhibitory effect of scutellarein on uridine 5'-diphosphate glucuronide transferases and cytochrome P450 enzymes, potentially posing safety risks.

Antioxidants had No Effects on the In-Vitro Permeability of BCS III Model Drug Substances.

Reformulation with addition of antioxidants is one potential mitigation strategy to prevent or reduce nitrosamine drug substance-related impurities (NDSRIs) in drug products. To explore whether there could be other approaches to demonstrate bioequivalence for a reformulated oral product, which typically needs in vivo bioequivalence studies to support the changes after approval, the effects of antioxidant on the in vitro permeability of BCS III model drug substances were investigated to see whether there could be any potential impact on drug absorption. Six antioxidants were screened and four (ascorbic acid, cysteine, α-tocopherol and propyl gallate) were selected based on their nitrosamine inhibition efficiencies. The study demonstrated that these four antioxidants, at the tested amounts, did not have observable impact on the in vitro permeability of the BCS III model drug substances across Caco-2 cell monolayers in the In Vitro Dissolution Absorption System (IDAS). An in vitro permeability study could be considered as part of one potential bioequivalence bridging approach for reformulated low-risk immediate release solid oral products and oral suspension products. Other factors such as the influence of antioxidants on intestinal transporter activities should be considered where appropriate.

Intestinal Targeted Nanogel with Broad-Spectrum Autonomous ROS Scavenging Performance for Enhancing the Bioactivity of trans-Resveratrol.

Introduction: To improve the bioavailability of trans-resveratrol (trans-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier, however, which makes practical application challenging. Methods: A nanogel (Ngel), as broad-spectrum autonomous ROS scavenger, was prepared using selenized thiolated sodium alginate (TSA-Se) and crosslinked with calcium lactate (CL) for loading trans-Res to obtain Ngel@Res, which maintained spherical morphology in the upper digestive tract but broke down in the lower digestive tract, resulting in trans-Res release. Results: Under protection of Ngel, trans-Res showed enhanced stability and broad-spectrum ROS scavenging activity. The synergistic mucoadhesion of Ngel prolonged the retention time of trans-Res in the intestine. Ngel and Ngel@Res increased the lifespan of Caenorhabditis elegans to 26.00 ± 2.17 and 26.00 ± 4.27 days by enhancing the activity of antioxidases, upregulating the expression of daf-16, sod-5 and skn-1, while downregulating the expression of daf-2 and age-1. Conclusion: This readily available, intestinal targeted selenized alginate-based nanogel effectively improves the bioactivity of trans-Res.

Development of Lipid Polymer Hybrid Nanoparticles of Abietic Acid: Optimization, In-Vitro and Preclinical Evaluation.

The objective of the current research was to develop abietic acid (AA)-loaded hybrid polymeric nanoparticles (HNPs) for anti-inflammatory and antioxidant activity after oral administration. AAHNPs were developed by microinjection technique and optimized by 3-factor 3-level Box-Behnken design. The AAHNPs were evaluated for morphology, FTIR, X-ray diffraction, in-vitro release, ex-vivo permeation, in-vitro antioxidant, and in-vivo anti-inflammatory activity. The optimized AAHNPs (AAHNPsopt) displayed 384.5 ± 6.36nm of PS, 0.376 of PDI, 23.0 mV of ZP, and 80.01 ± 1.89% of EE. FTIR and X-ray diffraction study results revealed that AA was encapsulated into a HNPs matrix. The AAHNPsopt showed significant (P < 0.05) high and sustained release of AA (86.72 ± 4.92%) than pure AA (29.87 ± 3.11%) in 24h. AAHNPsopt showed an initial fast release of AA (20.12 ± 3.07% in 2h), which succeeded in reaching the therapeutic concentration. The AAHNPsopt showed 2.49-fold higher ex-vivo gut permeation flux than pure AA due to the presence of lipid and surfactant. The AAHNPsopt exhibited significantly (P < 0.05, P < 0.01, P < 0.001) higher antioxidant activity as compared to pure AA at each concentration. AAHNPsopt formulation displayed a significantly (P < 0.05) higher anti-inflammatory effect (21.51 ± 2.23% swelling) as compared to pure AA (46.51 ± 1.74% swelling). From the in-vitro and in-vivo finding, it was concluded that HNPs might be a suitable carrier for the improvement of the therapeutic efficacy of the drug.