Improvement Of Bioavailability Research Articles

Bioavailability transition path of phosphorus species during the sewage sludge incineration process

Sewage sludge incineration ash (SSIA) is rich in phosphorus (P), thus being considered as a reliable source of phosphorus recovery. Different P species behaved significant bioavailability. Based on this, a comprehensive investigation into the bioavailability transition path of P species during sewage sludge (SS) incineration was conducted. P predominantly existed in the form of inorganic phosphorus (IP) in SS with a higher concentration of non-apatite inorganic phosphorus (NAIP) and less concentration of apatite inorganic phosphorus (AP). During the SS incineration process, OP existed in the flocs and cell structures of SS underwent destruction, the released P then combined with metal elements such as Ca, Mg, Fe, and Al to form AP species (Ca/Mg–P) and NAIP species (Fe/Al/Mn–P), and the NAIP decomposition to release into gas phase. This was the initial step for enhancing the bioavailability of P species. As temperature increased and the incineration process progressed, the low-temperature-resistant NAIP dissociated, and the metal-binding sites of Al, Fe and Mn in NAIP species were gradually replaced by the Ca and Mg thus forming thermal stability AP species (Ca/Mg–P, such as CaHPO4, Ca2PO4Cl, and Mg3(PO4)2 et al.). This step was crucial for the bioavailability improvement of P species during the incineration process. Therefore, the IP proportions in TP were extremely high (＞98%), and this value gradually increased as incineration temperature raised. The higher incineration temperature, the lower NAIP concentration and higher AP concentration. Besides, additives such as coal/rice husk/eggshell played a significant affect. Additives wither higher Ca content were inclined to react with P to form Ca/Mg–P (AP), while the presence of SO2 would react with Ca metals to form CaSO4 thus inhibiting the formation of AP species (such as CaHPO4 and CaPO4Cl). This results could provide theoretical support for the efficient and directional migration of P during sewage sludge incineration.

Flavonoid-Labeled Biopolymer in the Structure of Lipid Membranes to Improve the Applicability of Antioxidant Nanovesicles.

Nanovesicles produced with lipids and polymers are promising devices for drug and bioactive delivery and are of great interest in pharmaceutical applications. These nanovesicles can be engineered for improvement in bioavailability, patient compliance or to provide modified release or enhanced delivery. However, their applicability strongly depends on the safety and low immunogenicity of the components. Despite this, the use of unsaturated lipids in nanovesicles, which degrade following oxidation processes during storage and especially during the proper routes of administration in the human body, may yield toxic degradation products. In this study, we used a biopolymer (chitosan) labeled with flavonoid (catechin) as a component over a lipid bilayer for micro- and nanovesicles and characterized the structure of these vesicles in oxidation media. The purpose of this was to evaluate the in situ effect of the antioxidant in three different vesicular systems of medium, low and high membrane curvature. Liposomes and giant vesicles were produced with the phospholipids DOPC and POPC, and crystalline cubic phase with monoolein/DOPC. Concentrations of chitosan-catechin (CHCa) were included in all the vesicles and they were challenged in oxidant media. The cytotoxicity analysis using the MTT assay (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) revealed that concentrations of CHCa below 6.67 µM are non-toxic to HeLa cells. The size and zeta potential of the liposomes evidenced the degradation of their structures, which was minimized by CHCa. Similarly, the membrane of the giant vesicle, which rapidly deteriorated in oxidative solution, was protected in the presence of CHCa. The production of a lipid/CHCa composite cubic phase revealed a specific cubic topology in small-angle X-ray scattering, which was preserved in strong oxidative media. This study demonstrates the specific physicochemical characteristics introduced in the vesicular systems related to the antioxidant CHCa biopolymer, representing a platform for the improvement of composite nanovesicle applicability.

Innovative Approach to Enhance Bioavailability of Birch Bark Extracts: Novel Method of Oleogel Development Contrasted with Other Dispersed Systems.

Birch outer bark extract (BBE), containing pentacyclic triterpenes such as betulin, lupeol, and betulinic acid, is a widely recognized natural product renowned for its diverse pharmacological effects. However, its limited water solubility restricts its bioavailability. Therefore, the main objective is to enhance the bioavailability of BBE for pharmaceutical use. In this study, we aimed to develop a dispersion system utilizing a unique oleogel-producing method through the recrystallization of BBE from an ethanol solution in the oil phase. We generated an oleogel that demonstrates a notable 42-80-fold improvement in betulin and lupeol peroral bioavailability from BBE in Wistar rats, respectively. A physical paste-like BBE hydrogel developed with antisolvent precipitation showed a 16-56-fold increase in the bioavailability of betulin and lupeol from BBE in rat blood plasma, respectively. We also observed that the repeated administration of the BBE oleogel did not exhibit any toxicity at the tested dose (38.5 mg/kg betulin, 5.2 mg/kg lupeol, 1.5 mg/kg betulinic acid daily for 7 days). Betulin and betulinic acid were not detected in rat heart, liver, kidney, or brain tissues after the peroral administration of the oleogel daily for 7 days. Lupeol was found in rat heart, liver, and kidney tissues.

Improvement of solubility, dissolution, and bioavailability of phenytoin intercalated in Mg-Al layered double hydroxide.

Layered double hydroxides (LDHs) are highly effective drug delivery systems, owing to their capacity to intercalate or adsorb biomaterials, flexible structure, swelling property, high stability, good biocompatibility, and ease of synthesis. Phenytoin (PHT) is an antiseizure BCS (Biopharmaceutics Classification System) class II drug, presenting low aqueous solubility. Therefore, the current study aimed at increasing its solubility, dissolution, and bioavailability. PHT was intercalated to the MgAl-LDH formed in situ and successful intercalation to form MgAl-PHT-LDH was confirmed by FTIR, PXRD, DSC, and TGA. Examination of particle size and morphology (by photon correlation spectroscopy and electron microscopy, respectively) confirmed the formation and intercalation of nanostructured LDH. Intercalation enhanced the saturation solubility of PHT at 25°C in 0.1N HCl and phosphate buffer (pH 6.8) by 6.57 and 10.5 times respectively. The selected drug excipient powder blend for the formulation of MgAl-PHT-LDH tablets exhibited satisfactory properties in both pre-compression parameters (angle of repose, bulk density, tapped density, Carr's index, and Hausner ratio) and tablet characteristics (weight variation, thickness, hardness, friability, content uniformity, and disintegration time). MgAl-PHT-LDH tablets showed better dissolution of PHT compared to unprocessed PHT tablets at all time points. Oral bioavailability of MgAl-PHT-LDH tablets and unprocessed PHT tablets was tested in two groups of Sprague Dawley rats based on analysis of serum levels of both forms of PHT by UPLC-ESI-MS/MS serum. MgAl-PHT-LDH tablets demonstrated a relative bioavailability of 130.15% compared to unprocessed PHT tablets, confirming a significantly higher oral bioavailability of MgAl-PHT-LDH. In conclusion, MgAl-PHT-LDH could provide a strategy for enhancing solubility, dissolution, and thereby bioavailability of PHT, enabling the evaluation of theclinical efficacy of MgAl-PHT-LDH tablets for the treatment of seizures at lower PHT doses.

Novel radioiodinated desvenlafaxine-loaded lipid nanocapsule for brain delivery.

Lipid nanocapsules (LNCs) are lipid nanocarriers developed for drug delivery enhancement. The antidepressant drug desvenlafaxine (DSV) was entrapped in LNC to improve its brain delivery. Different DSV-loaded LNCs formulae using different oils and surfactants were studied to obtain the optimum formula for further studies. In vivo biodistribution studies were done using Swiss albino mice by intravenous injection of DSV-loadedLNCs by radioiodination technique. The optimum DSV-loaded LNC formula was obtained by using Labrafil® M1944CS as the oil and Solutol® HS15 as the surfactant in the ratio of 1:1, with a particle size of 34.28 ± 0.41 nm, a polydispersity index of 0.032 ± 0.05, a zeta potential of -25.77 ± 1.41, and good stability for up to 6 months. The in vivo biodistribution and pharmacokinetics data ensure the bioavailability improvement for DSV brain delivery as Cmax and AUC(1-t) increased more than double for intravenously DSV-loaded LNCs compared with the DSV solution. In conclusion, the results obtained from this study give an insightinto the great potential of using DSV-loaded LNC for the enhancement of brain delivery.

Development of Self-Nano-Emulsifying Drug Delivery System for Gemcitabine: In Vitro and Ex Vivo Evaluation

Researchers often aim to develop novel drug delivery systems to overcome the barriers associated with conventional drug delivery systems. Therefore, GEM (Gemcitabine), an anti-cancerous drug, belonging to the Biopharmaceutics Classification System (BCS) Class III with reduced permeability, is an important challenge. Self-nano-emulsifying drug delivery system (SNEDDS) was opted to be designed in such a way that it improves the permeability of GEM. From compatibility and solubility studies, Kolliphor RH40, castor oil, and polyethylene glycol-400 were chosen in optimized ratios for preparation into GEM-SNEDDS. GEM-SNEDDS F3 showed -12.1±6.83 mV zeta-potential, 0.406 PDI, and 94.81±82.73 nm particle size when tested for in vitro and ex vivo studies, F3 showed improved GEM release in simulated gastric fluid and simulated intestinal fluid in vitro and enhanced permeability ex vivo. These factors are prerequisites for the improvement of poor bioavailability of GEM. From stability studies, it was evident that F3 retained its physical stability at several stability conditions and in drug encapsulation and loading. Hence, we developed GEM-SNEDDS as a novel drug delivery system for increasing the permeability and, in turn, the oral bioavailability of GEM.

Molecular dynamics study on micelle-small molecule interactions: developing a strategy for an extensive comparison

Theoretical predictions of the solubilizing capacity of micelles and vesicles present in intestinal fluid are important for the development of new delivery techniques and bioavailability improvement. A balance between accuracy and computational cost is a key factor for an extensive study of numerous compounds in diverse environments. In this study, we aimed to determine an optimal molecular dynamics (MD) protocol to evaluate small-molecule interactions with micelles composed of bile salts and phospholipids. MD simulations were used to produce free energy profiles for three drug molecules (danazol, probucol, and prednisolone) and one surfactant molecule (sodium caprate) as a function of the distance from the colloid center of mass. To address the challenges associated with such tasks, we compared different simulation setups, including freely assembled colloids versus pre-organized spherical micelles, full free energy profiles versus only a few points of interest, and a coarse-grained model versus an all-atom model. Our findings demonstrate that combining these techniques is advantageous for achieving optimal performance and accuracy when evaluating the solubilization capacity of micelles.Graphical abstractAll-atom (AA) and coarse-grained (CG) umbrella sampling (US) simulations and point-wise free energy (FE) calculations were compared to their efficiency to computationally analyze the solubilization of active pharmaceutical ingredients in intestinal fluid colloids.

Pharmacokinetic assessment of Natural Anticancer Berberine Chloride in presence and absence of some Herbal Bioenhancers in rabbit model

The present study investigated the influence of pretreatment of herbal bioenhancers quercetin, curcumin and piperine, separately on pharmacokinetic profile of berberine chloride (BBC) in rabbit model. Initially, ex-vivo permeability studies were conducted to optimize the batches of drug and bioenhancer combinations, wherein, the optimized batches were subjected for in-vivo pharmacokinetic studies in rabbits via single oral dose. All experimental procedures on animals were conducted according to the CPCSEA guidelines. The collection of blood samples were done at predetermined time intervals appropriately processed and analyzed by HPLC method. The data were processed using software and pharmacokinetic parameters (AUC, Cmax, Tmax, Kel) of BBC were obtained. The results showed that piperine exhibited strongest bioenhancing effect on BBC absorption as compared to quercetin and curcumin. The Cmax of BBC was increased by 626.53%, 401.86% and 168.60% for piperine, quercetin and curcumin optimized batches, respectively, with notable reduction in Tmax as compared to BBC (Control). These bioenhancers showed outstanding enhancement in the pharmacokinetic profile of BBC. BBC has been reported to be P-glycoprotein (P-gp) substrate, exhibiting extremely poor bioavailability, which could be successfully overcome by pre-treatment with bioenhancers, attributed to bioenhancer mediated inhibition of the P-gp efflux pump and drug metabolizing enzymes. This improvement in bioavailability and other pharmacokinetic parameters of BBC in presence of bioenhancers would be expected to reduce dose, dosing frequency and toxicity of BBC, thereby contributing improved patient compliance. Thus, it could be concluded that, pre-treatment of herbal bioenhancers could be an effective approach to improve pharmacokinetics of drug like molecules.

Development and Optimization of Enzalutamide Nanosuspension by Design of Experiments for Dissolution Enhancement

Enzalutamide is an anticancer molecule used for prostate cancer. The goal of the study was to develop a nanosuspension of enzalutamide in order to improve its solubility and dissolution properties. High-speed homogenization method was employed to formulate the nanosuspension. Preliminary studies suggested the amount of stabilizer, homogenization time and homogenization speed as critical variables to be taken for the optimization process. Box-Behnken design was employed for the optimization of process and formulation variables. Nanosuspension was evaluated for particle size, PDI, zeta potential, and in-vitro drug release at 10 minutes (D10) studies. Regression analysis suggested the influence of independent variables on the responses. The optimized batch obtained from the overlay plot exhibited 198.36 nm of particle size, (-33.27 mV of zeta potential and 80.47% of D10 values). The characterization studies i.e., DSC, and XRD illustrated retention in crystallinity of the drug. The drug and formulation were found to be stable over a 6-month period in accelerated stability testing. Using high speed homogenization method, the particle size of the formulation was reduced to nano-size, which was further responsible for the improvement in dissolution and bioavailability of the drug.

Comparative study of different biological processing methods on nutritional composition and bioactivity of whole‐grain wheat

AbstractBackground and ObjectivesBiological processing is considered one of the most effective technologies used to eliminate adverse traits and improve the quality of cereal. To compare the effects of different biological processing methods on the nutritional value and bioactivity of whole‐grain wheat (WGW), solid‐state fermentation (SSF), germination (GT), solid‐state fermentation (SSF), germination (GT), and phytase treatment (PT) were performed.FindingsAfter biological processing, protein, insoluble dietary fiber, and bound flavonoid contents significantly increased, while phytate, bound phenolic, and free flavonoid contents obviously decreased. The molar ratio of phytate content to mineral content, including PA/Ca, PA/Fe, and PA/Zn, significantly reduced by 13.8%–42.0%, 8.4%–73.4%, and 17.9%–45.0%, respectively, suggesting the improvement of mineral bioavailability. The greatest reduction of phytate content was found in WGW after PT. In comparison to SSF and PT, GT significantly improved phenolic content and 2,2‐azinobis (3‐ethylbenzothiazoline‐6‐sulfonic acid) and 1, 1‐diphenyl‐2‐picrylhydrazyl free radical scavenging abilities of free phenolic extract in WGW. As compared to GT and PT, the ORAC of the free phenolic extract in WGW obviously improved after SSF with strains of Lactobacillus plantarum, Saccharomyces cerevisiae, and Monascus sp.ConclusionsOverall, SSF, GT, and PT showed high efficiency in phytate degradation, and GT and SSF, in particular, improved the nutritional value and bioactivity of WGW.Significance and NoveltyThis study provides data supporting the use of different biological processing methods based on different objectives when preparing WGW products.

Comprehensive Update on Carotenoid Colorants from Plants and Microalgae: Challenges and Advances from Research Laboratories to Industry.

The substitution of synthetic food dyes with natural colorants continues to be assiduously pursued. The current list of natural carotenoid colorants consists of plant-derived annatto (bixin and norbixin), paprika (capsanthin and capsorubin), saffron (crocin), tomato and gac fruit lycopene, marigold lutein, and red palm oil (α- and β-carotene), along with microalgal Dunaliella β-carotene and Haematococcus astaxanthin and fungal Blakeslea trispora β-carotene and lycopene. Potential microalgal sources are being sought, especially in relation to lutein, for which commercial plant sources are lacking. Research efforts, manifested in numerous reviews and research papers published in the last decade, have been directed to green extraction, microencapsulation/nanoencapsulation, and valorization of processing by-products. Extraction is shifting from conventional extraction with organic solvents to supercritical CO2 extraction and different types of assisted extraction. Initially intended for the stabilization of the highly degradable carotenoids, additional benefits of encapsulation have been demonstrated, especially the improvement of carotenoid solubility and bioavailability. Instead of searching for new higher plant sources, enormous effort has been directed to the utilization of by-products of the fruit and vegetable processing industry, with the application of biorefinery and circular economy concepts. Amidst enormous research activities, however, the gap between research and industrial implementation remains wide.

Effects of L-Glutamine on Biomarkers of Response in Sickle Cell Disease: A Pharmacokinetics-Pharmacodynamics Analysis

OralL-glutamine (Endari®) has been approved by the US-FDA to reduce the acute complications of sickle cell disease (SCD) in patients at least 5 years of age. L-glutamine has several roles in the body including de novo synthesis of intracellular glutathione which acts as an antioxidant. However, the mechanisms of action by which L-glutamine could reduce complications in SCD require further investigation. Additionally, there are no known biomarkers to assess response to L-glutamine therapy. We conducted an open-label, dose-ascending trial (NCT04684381) of L-glutamine in pediatric (n=4) and adult (n=4) participants with SCD as well as in adult healthy volunteers (n=4) (Table 1). Over a three-week trial period with 4 study visits, serial blood samples were collected to define the pharmacokinetics (PK), pharmacodynamics (PD), and PK-PD interactions of L-glutamine using a broad panel of laboratory investigations including amino acid concentrations, blood counts, percentage of dense red blood cells (%DRBC), whole blood viscosity, osmotic and oxygen gradient ektacytometry, and reactive oxygen species (ROS) of reticulocytes (ROS retic) and mature red blood cells (ROS RBC). In PK-PD analysis of amino acids, we focused analysis on arginine (Arg), citrulline (Cit), and ornithine (Orn) based on the hypothesis that L-glutamine improves endothelial function by increasing arginine bioavailability and augmenting nitric oxide (NO) production. Peak arginine concentration was directly correlated with both the maximum L-glutamine concentration (C max p=0.001) and area-under-the curve (AUC) (p=0.047) indicating improvement in arginine bioavailability, but there was no significant linear correlation with either the Arg:Orn or Arg:(Orn+Cit) ratios. In PK-PD analysis of osmotic gradient ektacytometry, L-glutamine C max was directly correlated with the elongation maximum (EI max), noted in all participants at visit 4 (p=0.033). In SCD participants, L-glutamine C max was inversely correlated with O hyper (osmolality at EI max/2) at visits 3 (p=0.044) and 4 (p=0.004). In PK-PD analysis of oxygen gradient ektacytometry in SCD participants, L-glutamine C max was inversely correlated with the point of sickling (POS) at visit 3 (p=0.005) but not at visit 4 (p=0.054). Together, these findings suggest that although L-glutamine may decrease cellular hydration (decreased O hyper) it may increase RBC deformability (increased EI max) and delay the onset of sickling after hypoxia (decreased POS). In PK-PD analysis of viscometry, higher L-glutamine C max was associated with higher whole blood viscosity measurements at all shear rates (p<0.05). However, L-glutamine C max was also directly correlated with hematocrit-to-viscosity ratio (HVR) at the highest shear rates in the overall population at visit 4 (p<0.05). In addition, L-glutamine C max for SCD participants was associated with increased hemoglobin concentration, an effect that was observed at visit 4 (p=0.025), and increased %DRBC, an effect detected at visits 3 (p=0.008) and 4 (p=0.007). In PK-PD analysis of ROS, L-glutamine AUC was inversely correlated with ROS Retic (p=0.024), but not ROS RBC, in all participants at visit 3. When considered as total ROS Retic (calculated as ROS retic × absolute reticulocyte count), there was a similar inverse correlation with glutamine AUC in SCD participants, although not statistically significant. In contrast to all other biomarkers, L-glutamine C max was not correlated with any ROS measurement. This PK-PD analysis of L-glutamine reveals biological effects that alter RBC characteristics and could modify SCD-related complications, with a complex interplay summarized in Figure 1. Prospective studies can validate these biomarkers and be used to monitor the effects of L-glutamine therapy in SCD patients.

Recent Nanoscale Carriers for Therapy of Alzheimer's Disease: Current Strategies and Perspectives.

This review covers nanotherapeutic strategies for solving the global problems associated with Alzheimer's disease (AD). The most dramatic factor contributing humanistic, social and economic urgency of the situation is the incurability of the disease, with the drug intervention addressing only AD symptoms and retarding their progress. Key sources behind these challenges are the inability of the early diagnosis of AD, the lack of comprehensive information on the molecular mechanism of the pathogenesis, the bloodbrain barrier obstacles, and the insufficient effectiveness of currently available drugs and therapeutic strategies. The application of nanocarriers allows part of these problems to be solved, together with the improvement of drug bioavailability, prolonged circulation, and overcoming/bypassing the biological barriers. To this date, numerous types and subtypes of nanocarriers are developed and reviewed, the majority of which can be adapted for the treatment of various diseases. Therefore, herein, nanotherapy strategies are specifically categorized in term of the administration routes of AD medicines, with the noninvasive, i.e., transdermal, oral, and intranasal routes emphasized. Further, benefits/ limitations of various nanocarriers are discussed, and perspectives of their application are highlighted.

Amelioration of Acute Alcoholic Liver Injury via Attenuating Oxidative Damage and Modulating Inflammation by Means of Ursodeoxycholic Acid-Zein Nanoparticles.

Ursodeoxycholic acid (UDCA) has been broadly adopted for the clinical treatment of hepatic and biliary diseases; however, its poor water-solubility becomes an obstacle in wide applications. To overcome these challenges, herein, a two-tier UDCA-embedded system of zein nanoparticles (NPs) along with a polyelectrolyte complex was designed under facile conditions. Both the UDCA-zein NPs and their inclusion microcapsules showed a spherical shape with a uniform size. A typical wall plus capsule/core structure was formed in which UDCA-zein NPs distributed evenly in the interior. The UDCA inclusion microcapsules had an encapsulation rate of 67% and were released in a non-Fickian or anomalous transport manner. The bioavailability and efficacy of UDCA-zein NPs were assessed in vivo through the alcoholic liver disease (ALD) mouse model via intragastric administration. UDCA-zein NPs ameliorated the symptoms of ALD mice remarkably, which were mainly exerted through attenuation of antioxidant stress levels. Meanwhile, it notably upregulated the intestinal tight junction protein expression and improved and maintained the integrity of the mucosal barrier effectively. Collectively, with the improvement of bioavailability, the UDCA-zein NPs prominently alleviated the oxidative damage induced by alcohol, modulating the inflammation so as to restore ALD. It is anticipated that UDCA-zein NPs have great therapeutic potential as sustained-nanovesicles in ALD treatment.

Observing nanotechnology in herbal medicine

Application of nanotechnology in herbal medicine promises promising improvements in medication delivery, bioavailability, and therapeutic efficacy. Nanotechnology has become a transformational tool in many industries. Even while traditional herbal remedies are abundant in bioactive chemicals, they frequently suffer from issues like low stability, poor solubility, and ineffective absorption by the body. By making it possible to encapsulate herbal ingredients in nanoparticles and improving their solubility, targeting abilities, and controlled release, nanotechnology overcomes these constraints. Reviewing current advancements in nanoparticle formulations, including liposomes, polymeric nanoparticles, and nanoemulsions for herbal extracts, this research investigates the nexus between nanotechnology and herbal medicine. The advantages of nano-herbal formulations are covered, including the possibility of site-specific drug administration, less toxicity, and enhanced pharmacokinetics. This investigation also explores safety evaluations, regulatory issues, and the difficulties of increasing output. Combining nanotechnology with traditional herbal medicine not only brings back the benefits of age-old cures but also opens the door to safer, more accessible, and more effective treatment choices in contemporary medicine.

Natural microbial surfactant containing self-nanoemulsifying formulation with improved performance of paclitaxel therapy: A newer avenue in breast cancer treatment

Due to the presence of a high concentration of surfactants (e.g., Cremophor EL, Tween 80), paclitaxel (PTX) drug delivery systems administered orally and intravenously demonstrate severe toxicity. In the current research work, a unique self-nanoemulsifying drug delivery system (SNEDDS) comprising surfactin, a microbial biosurfactant was used for reducing the formulation toxicity and improving the biopharmaceutical performance. The preformulation study including solubility analysis indicated suitability of corn oil as the natural lipophile. Nanoemulsion boundaries were delineated by aqueous titration of the lipid phase (ethyl oleate: plurol oleique), surfactants (Tween 80 and Surfactin) and cosolvent (Transcutol HP) to identify the optimum compositions on the basis of formulation quality attributes with globule size <250 nm, emulsification time <3 min and in vitro drug release >85% in 60 min. Biocompatibility evaluation of PTX-Surfactin SNEDDS on rat hepatocytes by H2DCF assay to determine the ROS level indicated an insignificant increase in fluorescence intensity, while PTX Tween 80-SNEDDS showed nearly 20% increase in ROS levels compared to the control cells. Furthermore, histopathology examination showed the absence of any signs of inflammation from intestinal segments treated with PTX Surfactin-SNEDDS, while PTX Tween 80-SNEDDS revealed infiltration of cells and the presence of inflammation on the intestinal villous microstructures. The anticancer activity evaluation by in vitro cytotoxicity on MCF-7 cells showed PTX Surfactin-SNEDDS and PTX Tween 80-SNEDDS with IC50 of 2.65 μM and 11.52 μM, respectively, while PTX suspension showed IC50 of 18.5 μM. Moreover, blank Surfactin-SNEDDS showed IC50 of 15.23 μM, while no cytotoxicity was observed for blank Tween 80-SNEDDS. Overall, the study interpreted high suitability of biosurfactant for developing the self-nanoemulsifying formulation of PTX with enhanced bioavailability, biocompatibility and synergistic improvement in the anticancer activity over the formulations containing synthetic surfactant.

Assessing stress responses in potherb mustard (Brassica juncea var. multiceps) exposed to a synergy of microplastics and cadmium: Insights from physiology, oxidative damage, and metabolomics

Both microplastics (MPs) and cadmium (Cd) are common contaminants in farmland systems, is crucial for assessing their risks for human health and environment, and little research has focused on stress responses mechanisms of crops exposed to the combined pollution. The present study investigated the impact of polyethylene (PE) and polypropylene (PP) microplastics (MPs), in combination with Cd, on the physiological and metabolomic changes as well as rhizosphere soil of potherb mustard. Elevated levels of PEMPs and PPMPs were found to impede nutrient uptake in plants while promoting premature flowering, and the concomitant effect is lower crop yields. The substantial improvement in Cd bioavailability facilitated by MPs in rhizosphere soil, especially in high concentrations of MPs, then elevated bioavailability of Cd contributed to promoted Cd accumulation in plants, with distinct effects depending on the type and concentration of MPs. The presence of MPs Combined exposure to high concentrations of MPs and Cd resulted in alterations in plant physiology and metabolomics, including decreased biomass and photosynthetic parameters, elevated levels of reactive oxygen species primarily H2O2, increased antioxidant enzyme activities, and modifications in metabolite profiles. Overall, our study assessed the potential impact on food security (the availability of cadmium to plant) and crops stress responses regarding the contamination of MPs and Cd, providing new insights for future risk assessment in agriculture.

Recent advances in drug substance development – prodrug strategies for enhancing the bioavailability and potency of antiviral nucleosides

Bioavailability is a prerequisite for drug activity. In vivo bioavailability (intestinal permeability), linked to drug substance solubility and drug product dissolution, became the basis of Gordon L. Amidon’s Biopharmaceutical Classification System. One method of improving the drug substance’s bioavailability is to modify its structure chemically, leading to increased lipophilicity and the ability to penetrate the phospholipid bilayer of the cell membrane. These modifications, known as prodrug strategies, involve derivatizing the drug substance by introducing substituents that reduce the hydrophilicity of the molecule. The present mini-review outlines the examples of Christopher McGuigan’s prodrug strategies used to obtain antiviral nucleosides with enhanced bioavailability and activity. These strategies primarily involve forming and optimizing the structure of esters and amino acid esters, phosphoramidates, octadecyl phosphates, and bis-pivaloxymethyl phosphates. The review discusses the optimization of the phosphoramidate prodrug moiety of the SARS-CoV-2 antiviral nucleoside remdesivir in detail. It presents the resulting improvement in bioavailability and antiviral activity. Moreover, it focuses on the modern prodrug strategy as one of the major recent advances in drug substance development. This strategy effectively optimized physicochemical properties and improved the functional activity of the existing drug substances and drug substance candidates for the first time.

Soft-capsule formulation of a re-esterified triglyceride omega-3 employing self-emulsifying technology and bioavailability evaluation in healthy volunteers

Despite the superior clinical efficacy of the re-esterified triglyceride (rTG) form compared to the ethylester form, few studies have been conducted on improving the bioavailability of the rTG form of omega-3 oil. The aim of study was to evaluate the effect of self emulsifying formulation on the improvement of bioavailability of rTG form of omega-3 oil.To develop a re-esterified triglyceride (rTG) soft capsule, an rTG-loaded self-emulsifying delivery system (SEDS) was designed using coconut oil, polysorbate 80, and lecithin. Candidate formulations were designed from a phase-diagram study and optimal SEDS formulations containing 85% of high omega-3 (ω−3) oils were screened from the evaluation of droplet size distribution, measurement of oil floating area and emulsion turbidity. The selected, optimized rTG SEDS formulation was filled into a soft capsule (NOVASEDS) and applied to a sequence-randomized, double-blind, single-dose, and two-way crossover clinical study (n = 44), and the the bioavailability of NOVASEDS was compared with that of a ‘raw’ rTG capsule (rTG OMEGA3) as control. The droplet size (D50) formed from the candidate formulations was approximately 30–45 μm, and the optimal formulation showed a unimodal particle distribution with the smallest oil floating area and small changes in turbidity after 24 h. Cmax and AUC from 0 to 24 h for NOVASEDS, calculated from docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and as the sum of DHA and EPA, were significantly higher (P < 0.05) than corresponding values for rTG OMEGA3. In conclusion, NOVASEDS formulated by SEDS technology enabled the manufacture of a high rTG payload soft capsule with improved bioavailability in human subjects.

Cyclodextrin MOFs modified dry powder inhalers quadruple bioavailability of luteolin to ameliorate fibrosing interstitial lung disease

Fibrosing interstitial lung disease (ILD) is a pathological condition that is highly heterogeneous and lethal, and has few effective treatment choices. Other than pirfenidone and nintedanib for the therapy of idiopathic pulmonary fibrosis, no medications are currently licensed for the treatment of ILD. Luteolin is a common flavonoid with multiple biological effects such as anti-inflammation but with poor solubility and absorption. In this study, we loaded luteolin into γ-cyclodextrin metal–organic frameworks (CD-MOFs) to deliver the medicine to the lungs using dry powder inhalers; in vitro pulmonary deposition results showed LUT@CDMOF had a high fine particle fraction (FPF) (59.77 ± 3.48%). LUT@CDMOF effectively inhibited ILD progression in the BLM-induced fibrosing ILD model rats. When compared to oral administration, the inhalation of LUT@CDMOF dry powder in rats showed considerable improvements in absorption and bioavailability, with a tmax of 0.08 h and a high absolute bioavailability (82%) of LUT (The AUC(0-t) and Cmax of inhal. LUT@CDMOF respectively increased about 4.03 times and 9.11 times, when compared with the i.g. LUT group). These studies demonstrate the potent anti-inflammatory activities of LUT@CDMOF. The inhaled LUT@CDMOF might be considered as a promising new strategy in the treatment of fibrosing ILD.