Poor Oral Absorption Research Articles

Analysis of gut microbiota metabolites of platycodin D and activity verification

As the main saponin component of Platycodon grandiflorum A.DC, Platycodin D has been reported to have an anti-obesity effect. Due to poor oral absorption, the intestinal microflora usually transforms saponins into potential bioactive substances. In this study, we profiled the metabolic changes of platycodin D by incubating it with intestinal microflora extracted from mice feces subjected to either a standard control diet or a high-fat diet. A UPLC-LTQ-Orbitrap-MS method was used for rapid analysis of the metabolic profile of platycodin D. A total of 10 compounds were identified 9 of which were assessed to be metabolized by intestinal microflora. Dehydroxylation and deglycosylation were the major metabolic process of platycodin D. The metabolic profile of platycodin D biotransformed by intestinal microflora was elucidated based on the metabolite information. Platycodin D and its metabolites had anti-inflammatory effects in LPS-stimulated RAW 264.7 cells. Only platycodin D could alleviate lipid accumulation in FFA-treated HepG2 cells.

Nano-encapsulation of EGCG in dextran 70-stabilized chitosan/SDS nanoparticles: Characterization, permeability behavior and oral bioavailability

Epigallocatechin gallate (EGCG) declares massive health benefits, while poor oral absorption and susceptibility to oxidation and degradation constrained clinical applications. EGCG-encapsulated chitosan/SDS nanoparticles coated with dextran 70（EDCSNs）were here prepared by ionic interaction. The nano-formulations stabilized by dextran 70 presented sizes less than <200 nm, > 30 mV zeta potential, excellent dispersion action and higher encapsulation efficiency, which outdistanced pluronic F-68 as stabilizer. Interaction mechanism of EGCG, chitosan, dextran 70 and SDS in EDCSNs were through hydrogen bond, ion–dipole and electrostatic of opposite charge. Compared with EGCG, EDCSNs demonstrated a superior stability and retention ability with the pH-responsive protection EGCG against degradation under the simulated gastrointestinal fluids. Furthermore, EDCSNs emanated remarkably antioxidant activity and permeability through the intestinal epithelial barrier. Oral administration of nano-formulations in rats evidently increased the plasma Cmax and area under-the-curve 1.95-fold than naked EGCG. Results evidenced that EDCSNs, as a new delivery system, has great potential improvement the stability of EGCG and enhancement the oral absorption and bioavailability.

Effects of Wuzhi Capsule on Whole-Blood Tacrolimus Concentration Levels: A Systematic Review and Meta-Analysis.

Wuzhi Capsule (WZC) is a traditional Chinese medicinal herb widely used to treat drug-induced hepatitis or liver dysfunction and is usually prescribed in China to increase tacrolimus concentration. Several studies with small sample sizes have shown that WZC can increase tacrolimus concentration levels in clinical practice. This study aimed to evaluate the effect of WZC on whole-blood tacrolimus concentration levels and safety. We searched 7 databases for randomized clinical trials (RCTs) and observational studies (OSs) comparing whole-blood tacrolimus concentration levels between WZC and non-WZC treatments. Data analysis was performed using Review Manager version 5.3. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Eleven studies involving 6 RCTs and 5 OSs were included. The meta-analysis indicated that whole-blood tacrolimus concentration levels in the WZC group was significantly higher than that of the non-WZC group [weighted mean difference = 1.38, 95% CI (confidence interval), 1.21-1.56, P < 0.001], and similar results were shown in all the subgroups of follow-up time, different primary disease, and different WZC doses. In the self-control OSs, the whole-blood tacrolimus concentration levels in the WZC group was significantly higher than the non-WZC group (weighted mean difference = 1.17, 95% CI, 0.71-1.64, P < 0.001). WZC was generally well tolerated and there was no significant difference in the incidence of adverse reactions between the 2 groups. WZC can increase whole-blood tacrolimus concentration levels. This may be an economical and practical treatment choice for patients, especially those with poor oral tacrolimus absorption capabilities. Nevertheless, RCTs and OSs with large sample sizes and high quality are needed in the future to confirm these positive results.

Development and In Vitro Evaluation of Nanoparticles of Silymarin Using Central Composite Design

Silymarin is a phytoconstituent derived from the plant Silybum marianum with poor oral absorption and bioavailability but possesses hepatoprotective activity, anticancer activity, cardioprotective, neuroprotective, stabilizing, anti-inflammatory, and antioxidant activity. Therefore, the current work aims to develop a nanoformulation of silymarin to increase bioavailability, reduce dosing frequency, minimize toxicity, and improve patient compliance. Silymarin nanoparticles were created via the ionic gelation technique, employing chitosan and TPP as the primary polymers. A central composite design was employed for formulation optimization. Chitosan and TPP were employed as independent variables, while particle size and encapsulation efficiency were considered as dependent variables. The prepared nanoparticles were evaluated through entrapment efficiency, in vitro drug release, and drug-excipient interaction studies. Thirteen experiments were conducted using the experimental runs created by the central composite design. The average particle size was between 149nm and 294nm. The encapsulation efficiency percentage was between 65.4% and 87.3%. The polydispersity index had a value of 0.437. The zeta potential of the optimized formulation was determined to be 38.1 mV. The compatibility studies between the drug and excipients were confirmed using Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetry. The successful encapsulation of silymarin within the polymer core was verified through scanning electron microscopy analysis. The silymarin-loaded nanoparticles were observed to have a significant drug release of 98,942.43% over 24 hours. The outcomes of the study of Silymarin nanoparticles showed a substantial increase in the dissolution rate, which can be ascribed to the changed solubility properties of the drug. This result is consistent with the stated aim of improving drug absorption. Keywords: Silymarin, nanoformulation, central composite design.

Research Progress on Quercetin's Biological Activity and Structural Modification Based on Its Antitumor Effects

AbstractQuercetin is a naturally existing flavonoid with numerous physiological effects, including antitumor activity. It functions as an antitumor agent by inducing apoptosis and inhibiting tumor cell development, preventing tumor cell invasion and metastasis, and reversing tumor multidrug resistance. Quercetin has limited therapeutic usefulness due to its low water solubility, poor oral absorption, and low bioavailability. New quercetin derivatives are being developed and manufactured via a variety of methods to address inadequacies and for utilization in disease prevention and therapy. The synthesis and anticancer effects of quercetin derivatives, as well as the structure‐activity relationship of quercetin derivatives, were explored, and the unique dosage forms of these derivatives were summarized to serve as a reference for future quercetin research and development.

Tea saponins as novel stabilizers for the development of diosmin nanosuspensions: Optimization and in vitro evaluation

Diosmin (DSN) is a plant-origin polyphenolic component that has attracted considerable interest for various physiological applications. Nevertheless, DSN shows high intersubject variation and poor oral absorption because of its poor solubility and permeability. This study examined the use of phytosaponins, specifically, tea saponins (TS), as novel stabilizers for optimizing and preparing diosmin nanosuspensions using top-down methods. The main formulation and process variables in particle size and polydispersity index were investigated by single-factor experiment optimization. The DSN nanocrystals were prepared and then characterized by electron microscopy, Fourier transform infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD). Compared with conventional stabilizers, TS exhibited better stabilizing performance at low concentrations. The lyophilized powder, which had a particle size 478.4 ± 9.4 nm after redispersion, coupled with mannitol as lyoprotectant showed good redispersibility. Electron microscopy revealed that the nanocrystals had an irregular and lamellar morphology. PXRD and FT-IR spectroscopy indicated that the crystallinity of DSN was reduced during the production process. DSN nanosuspensions significantly enhanced the accelerated dissolution rate due to the amorphous status and decreasing particle size. Overall, this study presents an advantageous solution to poor solubility and offers a reasonable strategy for expanding the application range of DSN.

Nanoformulations of curcumin: An alliance for effective cancer therapeutics

Cancer is intimidating in its diversity, genetics, epigenetics, pathology, diagnosis, and response to therapy. The high rate of recurrence and development of resistance to therapies hinder the prognosis and the inadvertent side effects of contemporary medications can reduce the quality of life in patients. These observations emphasize the need for multi-targeted treatments that are not only relatively safe and economical, but also provide a more effective alternative to the conventional treatment modalities. Over the last few decades, scientific data has demonstrated that curcumin has a wide range of anti-cancer effects that are orchestrated via affecting diverse cancer signaling pathways. Nonetheless, the therapeutic applicability of curcumin is severely limited due to its low water solubility, poor oral absorption, and rapid clearance. These limitations prompted the development of various curcumin formulations including nanotechnology based delivery systems for the prevention and treatment of cancers. Therefore, we aimed to review the potential benefits of nanocurcumin in treating various cancer. We conducted a comprehensive search on the PubMed database to identify relevant publications concerning the use of nanocurcumin in cancer treatment, utilizing the search term 'nanocurcumin and cancer'. This review summarizes various preclinical and clinical studies that highlight the anticancer activities of curcumin nanoformulations including cyclodextrin complexes, dendrimers, exosomes, liposomes, gold nanoparticles (NPs), graphene nanocomposites, magnetic NPs, micelles, nanogels, polymeric NPs and solid-lipid NPs (SLNs). We further presented cellular mechanisms and clinical investigations, thus, emphasizing its potential in cancer prevention and treatment or even as an adjuvant therapy with conventional drugs to enhance therapeutic results in cancer patients.

Designing novel piperine-vanillin nano-crystals for bioavailability enhancement

Piperine (PIP) exhibits various pharmacological effects including anti-inflammatory, antipyretic, anti-convulsant, and neuroprotective activity, but its poor water solubility and oral absorption limit its therapeutic uses. In the present study, nano-crystal technology was employed to enhance the dissolution rate and bioavailability of PIP. Piperine-vanillin (PIP-VN) nano-crystals were formulated by top-down and bottom-up techniques and evaluated both in vitro and in vivo. The results revealed that the PIP-VN nano-crystal exhibited an average particle size of 34.03 ± 0.51 nm. In the release study, PIP-VN nano-crystal performed 2.63-fold enhancement than PIP coarse powder. Upon oral administration, in the brain AUC0–24 of PIP-VN nano-crystal was significantly higher than PIP suspension. The brain/blood ratio of the drug for PIP-VN nano-crystal was higher than PIP suspension; indicating that administration of PIP-VN nano-crystal was superior for the delivery drug to the brain. PIP-VN nano-crystal showed AUC0–24 of 5.654 ± 0.230 ngh/mL in the brain which was more than PIP suspension (AUC0–24 of 2.025 ± 0.009 ngh/mL in the brain). From AUC data it may be concluded that brain delivery efficiency was improved using the nano-crystal approach. Compared with PIP coarse powder PIP-VN nano-crystals exhibit excellent performance in both in vitro and in vivo studies.

Boosting systemic absorption of peptides with a bioinspired buccal-stretching patch.

Biopharmaceuticals, including proteins and peptides, have revolutionized the treatment of a wide range of diseases, from diabetes and cardiovascular disorders to virus infections and cancer. Despite their efficacy, most of these macromolecular drugs require parenteral administration because of their high molecular weight and relative instability. Over the past 40 years, only a few oral peptide drugs have entered clinical trials, even when formulated with substantial amounts of permeation enhancers. To overcome the epithelial barrier, devices that inject drugs directly into the gastrointestinal mucosa have been proposed recently. However, the robustness and safety of those complex systems are yet to be assessed. In this study, we introduced an innovative technology to boost drug absorption by synergistically combining noninvasive stretching of the buccal mucosa with permeation enhancers. Inspired by the unique structural features of octopus suckers, a self-applicable suction patch was engineered, enabling strong adhesion to and effective mechanical deformation of the mucosal tissue. In dogs, this suction patch achieved bioavailability up to two orders of magnitude higher than those of the commercial tablet formulation of desmopressin, a peptide drug known for its poor oral absorption. Moreover, systemic exposure comparable to that of the approved oral semaglutide tablet was achieved without further optimization. Last, a first-in-human study involving 40 healthy participants confirmed the dosage form's acceptability, thereby supporting the clinical translatability of this simple yet effective platform technology.

Fabrication of pH-dependent solid dispersion for oral colon-targeted delivery of notoginsenoside R1 and its protective effects on ulcerative colitis mice

Notoginsenoside R1 (R1), which originated from the rhizomes and roots of Panax notoginseng, is classified as a Biopharmaceutical Classification System class III drug with good solubility but poor oral absorption. Although R1 can alleviate the inflammation of dextran sulfate sodium (DSS)-induced colitis in mice, the problem of acid degradation and low bioavailability limit its application. The purpose of this study was aimed to design one kind of pH-dependent solid dispersion for oral colon-targeted delivery of R1. Using Eudragit S100 (ES 100) and PEG 4000 as the pH-dependent carriers, R1 solid dispersion (R1-SD) was fabricated by solvent evaporation method. Scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction analysis indicated that R1-SD was completely formed, the surface was smooth surface and the strip crystal structure of R1 disappeared. The in vitro release profile of R1-SD (R1-ES 100-PEG 4000, 1:7:1, weight ratio) exhibited that R1-SD was not released in media simulating the gastric condition (pH 1.2), but better release characteristics of the drug could be obtained in media simulating the intestinal condition (less than 30% in pH 6.8 phosphate-buffered saline and more than 90% in pH 7.6 condition). The in vitro colon absorption test showed that the absorption rate and cumulative release of R1-SD were higher than those of R1. R1-SD and R1 had apparent protective effect on colon shortening, inflammatory infiltrating tissue injury, weight loss, diarrhea, blood stool in mice with ulcerative colitis induced by DSS, and the protective effect of R1-SD was better than that of R1, which indicated R1-SD has good practical application prospects.

A comparative study on the dependence potential of thienorphine and buprenorphine

Background: As part of research to discover partial opioid agonists for new treatments of opioid abuse and dependency, thienorphine, a buprenorphine analogue, was synthesised and reported to be a potent, long-acting oripavine in multiple mammalian models. Thienorphine binds non-selectively to μ-, δ-, and κ-opioid receptors, and partially stimulates μ- and/or κ-opioid receptors in vitro. Compared with buprenorphine, thienorphine exhibits better analgesic effects and has higher oral bioavailability. Poor oral absorption and dependence have hindered the use of buprenorphine for detoxification therapy and relapse prevention in the clinic. The addiction potential of thienorphine is unknown, and is worthy of in-depth investigation. Methods: In the present study, we conducted a comparison of thienorphine and buprenorphine with respect to their physical and psychological dependence liabilities, using a naloxone-induced withdrawal test, a conditioned place preference test, and a self-administration experiment in rats. Results: In contrast to chronic buprenorphine administration, we failed to observe any severe abstinence syndromes in mice or rats treated with thienorphine after naloxone challenge in a physical dependence model. Compared with the dependence potentials of buprenorphine, rats treated with chronic thienorphine did not show a place conditioning response, self-administration, or psychological dependence. Conclusions: We demonstrated that thienorphine has a lower potential than buprenorphine for physical and psychological dependence. Our results indicate that thienorphine might be a good candidate to treat opioid addiction.

Formulation and Characterization of Ursodeoxycholic Acid Nanosuspension Based on Bottom-Up Technology and Box-Behnken Design Optimization.

Ursodeoxycholic acid (UDCA) is a therapeutic agent used for the treatment of cholestatic hepatobiliary diseases in pediatric patients. It is a bile acid that presents high lipophilicity, and it belongs to Class II of the Biopharmaceutical Classification System (BCS), which exhibits low water solubility and high intestinal permeability, which leads to poor oral absorption. The objective of this work was to design and optimize UDCA nanosuspensions by means of the precipitation-ultrasonication method to improve the solubility, dissolution, and oral bioavailability of UDCA. A three-level, three-factor Box-Behnken design was used to optimize formulation variables and obtain uniform, small-particle-size UDCA nanosuspensions. The independent variables were: stabilizer percentage (X1), amplitude (X2), and sonication time (X3), and the dependent variable was the particle size (Y1). In the precipitation-ultrasonication method, UDCA was dissolved in acetone:PEG 400 (1:1 v/v) and quickly incorporated into the antisolvent (pre-cooled aqueous dispersion of HPMC E-15 0.3%), by means of intense sonication at 50 W for 5 min, controlling temperature through an ice water bath. The lyophilization efficacy was evaluated by means of a cryoprotective efficacy test, working with 10% maltose at -80 °C. The nanosuspensions were characterized by dynamic light scattering (DLS), X-ray diffraction, and scanning electron microscopy (SEM). The physicochemical stability was determined at 25 °C and 4 °C at 7, 14, 30, and 60 days, and the UDCA content was analyzed via HPLC-UV. An in vitro dissolution assay and an oral bioavailability study were performed in male Wistar rats. A significant impact was achieved in the optimized nanosuspension with 0.3% (stabilizer), 50 W (amplitude), and 5 min (sonication time), with a particle size of 352.4 nm, PDI of 0.11, and zeta potential of -4.30 mV. It presented adequate physicochemical stability throughout the study and the UDCA content was between 90% and 110%. In total, 86% of UDCA was dissolved in the in vitro dissolution test. The relative oral bioavailability was similar without significant statistical differences when comparing the lyophilized nanosuspension and the commercial tablet, the latter presenting a more erratic behavior. The pharmacokinetic parameters of the nanosuspension and the commercial tablet were Tmax (1.0 ± 0.9 h vs. 2.0 ± 0.8 h, respectively), Cmax (0.558 ± 0.118 vs. 0.366 ± 0.113 µM, respectively), ΔCmax (0.309 ± 0.099 vs. 0.232 ± 0.056, respectively), AUC (4.326 ± 0.471 vs. 2.188 ± 0.353 µg/mL.h, respectively, p < 0.02), and IAUC0-24h (2.261 ± 0.187 µg/mL.h vs. 1.924 ± 0.440 µg/mL.h, respectively). The developed nanosuspension presents an appropriate dosage and administration for pediatric patients. On the other hand, it exhibits an adequate absorption and UDCA oral bioavailability.

Fabrication of a protein-dextran conjugates formed oral nanoemulsion and its application to deliver the essential oil from Alpinia zerumbet Fructus

The injury of vascular endothelial cells caused by high glucose (HG) is one of the driving factors of vascular complications of diabetes. Oral administration is the most common route of administration for the treatment of diabetes and its vascular complications. Essential oil extracts from Chinese medicine possess potential therapeutic effects on vascular endothelial injury. However, low solubility and volatility of essential oils generally result in poor oral absorption. Development of nanocarriers for essential oils is a promising strategy to overcome the physiological barriers of oral absorption. In this study, a nanoemulsion composed of bovine serum albumin (BSA)-dextran sulfate (DS) conjugate and sodium deoxycholate (SD) was constructed. The nanoemulsions were verified with promoted oral absorption and prolonged circulation time. After the primary evaluation of the nanoemulsion, essential oil from Alpinia zerumbet Fructus (EOFAZ)-loaded nanoemulsion (denoted as EOFAZ@BD5/S) was prepared and characterized. Compared to the free EOFAZ, EOFAZ@BD5/S increased the protective effects on HG-induced HUVEC injury in vitro and ameliorative effects on the vascular endothelium disorder and tunica media fibroelastosis in a T2DM mouse model. Collectively, this study provides a nanoemulsion for the oral delivery of essential oils, which holds strong promise in the treatment of diabetes-induced vascular endothelial injury.

258-LB: Iridoid Glycoside Modulates Gut Microbiota and Ameliorates Nonalcoholic Fatty Liver Disease–Related Metabolic Disorders

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease closely associated with glucose and lipid metabolism disturbance. The development of herbal medicine interventions for NAFLD is presently a popular topic in pharmaceutical research. However, although many active natural ingredients have been reported as promising agents for NAFLD, their potential benefits are contrasted by their poor oral absorption. GG-01, an effective iridoid glycoside discovered from a clinical prescription of traditional Chinese medicine (TCM), is exposed first in the intestinal tract, and gut microbes may quickly react to GG-01. Therefore, it is intriguing to explore the role of gut microbiota and microbial metabolites in the beneficial effects of GG-01 on NAFLD-related disorders. Our research intends to commence with the intestinal nutritional characteristics of GG-01. Firstly, the crucial role of intestinal microbiota in the pharmacological effects of GG-01 is confirmed using different animal models. Subsequently, we identify the key microbes by combining high-throughput sequencing and an in vitro culture system of intestinal microbiota. We then focus on one of the key microbes, Akkermansia muciniphila, and elucidate how GG-01 can treat NAFLD-related metabolic disorders by stimulating the bile acid biotransformation of Akkermansia muciniphila based on “TCM-microbiome-host” interaction. Finally, we present a novel therapeutic strategy of the synergistic effect of Akkermansia muciniphila and GG-01 via TGR5 to activate epithelial regeneration, promote GLP-1 production, and further treat NAFLD-related metabolic disorders. We also propose GG-01 as a new type of probiotic for the treatment of NAFLD. Disclosure C. Xie: None. Y. Liu: None.

Cannabidiol-Decorated Berberine-Loaded Microemulsions Improve IBS-D Therapy Through Ketogenic Diet-Induced Cannabidiol Receptors Overexpression.

Berberine (BR) shows promise as a candidate for treating irritable bowel syndrome with diarrhea (IBS-D). However, the undesired physicochemical properties and poor oral absorption limit its clinical translation. A ketogenic diet (KD) can induce intestinal overexpression of cannabidiol (CB) receptors, which may offer a potential target for IBS-D-specific delivery of BR. The microemulsions loaded with BR and decorated with cannabidiol (CBD/BR-MEs) were developed through a one-step emulsion method. The pharmaceutical behaviors of the CBD/BR-MEs were measured using dynamic light scattering and high-performance liquid chromatography. The efficacy of the anti-IBS-D therapy was evaluated by assessing fecal water content, Bristol score, and AWR score. The intestinal permeability were assessed through immunofluorescent staining of CB1 and ZO-1, respectively. The signaling of CREB/BDNF/c-Fos was also studied along with immunofluorescent and immunohistochemical examination of brain sections. The CBD/BR-MEs, which had a particle size of approximately 30 nm and a surface density of 2% (wt%) CBD, achieved greater than 80% (wt%) encapsulation efficiency of BR. The pharmacokinetics performance of CBD/BR-MEs was significantly improved in the KD-fed IBS-D rats than the standard diet-fed ones, which is highly related to intestinal expression of CB1 receptors. The treatment with CBD/BR-MEs and KD exhibited evident comprehensive advantages over the other groups in terms of anti-IBS-D efficacy. CBD/BR-MEs and KD synergistically decreased intestinal permeability. Moreover, the treatment with CBD/BR-MEs and KD not only blocked the CREB/BDNF/c-Fos signaling in the brain but also decreased the levels of neurotrophic factors, neurotransmitters, and inflammatory cytokines in the serum of IBS-D model rats. Such a design represents the first attempt at IBS-D-targeted drug delivery for improved oral absorption and efficacy through KD-induced target exposure, which holds promising potential for the treatment of IBS-D.

The passive diffusion improvement of Vitamin B12 intestinal absorption by Gelucire that fit for commercialized production

Vitamin B12 (VB12) is a vital micronutrient to maintain the normal state of the hematopoietic system. It must be obtained from the diet since the human body cannot synthesize it. Moreover, the absorption of VB12 needs to be mediated by intrinsic factor on the gastrointestinal (GI) track. The abnormalities in the stomach or lack of such intrinsic factors may result in poor oral absorption of VB12. However, the very advanced formulation strategies were generally very costly and still in the development stage. Thus, the objectives of the present study were to increase the VB12 intestinal absorption by conventional excipients of Gelucire 44/14 (G44/14) or Labrasol, which could be potentially formulated as a cost effect balanced product.The in vitro Caco-2 cell model was applied for the absorption study. A novel VB12 solid dispersion was subsequently prepared and further characterized by Differential scanning calorimetry, Fourier transform infrared spectroscopy, and Scanning electron microscopy, respectively. The membrane permeability of the VB12 solid dispersion was finally evaluated using ex vivo rat everted gut sac method. The results suggested that G44/14 could significantly enhance the intestinal absorption of VB12 via P-glycoprotein inhibition in vitro (P < 0.01). The membrane permeability of VB12could be significantly (P < 0.01) improved by G44/14-VB12 solid dispersion at a proportion of carrier: drug ratio of 20:1.The liquidfied solid dispersion was finally directly filled in the hard gelatin capsules. In conclusion, the cheap and simplified process of VB12 complex prepared by G44/14 could potentially increase VB12 intestinal absorption, which may be liable to commercial manufacturing.

Preparation of Nanoparticles Loaded with Quercetin and Effects on Bacterial Biofilm and LPS-Induced Oxidative Stress in Dugesia japonica.

Quercetin is a kind of flavonol compound, which has been widely concerned because of its good pharmacological effects. However, its poor water solubility and poor oral absorption limit its application. To address the above problems, the optimal technological conditions for preparing quercetin-loaded chitosan sodium alginate nanoparticles (Q-CSNPs) were obtained through single-factor experiment method. Q-CSNPs were characterized by particle size analyzer, scanning electron microscope (SEM), transmission electron microscope (TEM), and Fourier transform infrared spectroscopy (FTIR). Biofilm experiment evaluated the antibacterial activity of five different concentrations of Q-CSNPs against Escherichia coli and Staphylococcus aureus. DPPH and hydroxyl radical scavenging experiments determined their antioxidant activity. The effect of Q-CSNPs labeled with FITC on the oxidative stress of planarian was determined. The results showed that quercetin was successfully encapsulated and had good antibacterial and antioxidant capacity in vitro. In vivo experiments of planarians also showed that Q-CSNPs could inhibit the oxidative stress induced by lipopolysaccharide (LPS) and especially alleviate the decrease of CAT activity and the increase of MDA content in planarians induced by LPS. After being supported by future in vivo studies, this preparation will provide research possibilities for the development of quercetin nano-drugs, quercetin dietary supplement, and so on.

Black ginger extract and its active compound, 5,7-dimethoxyflavone, increase intestinal drug absorption via efflux drug transporter inhibitions

Black ginger is used as an herbal medicine for self-care and health promotion. Black ginger extract has been shown to alter the function of transporters in several cell types. This study demonstrates the interaction between the extract and 5,7-dimethoxyflavone (DMF) on drug efflux mediated by breast cancer resistance proteins (BCRP) and P-glycoprotein (P-gp) in Caco-2 cells and heterologous cell systems [Madin-Darby canine kidney type II (MDCKII) stably transfected with human BCRP (MDCKII/BCRP) or human P-gp (MDCKII/P-gp)]. The transepithelial flux of 3H-Digoxin and 3H-Estrone sulfate, prototypic substrates of P-gp, and BCRP, respectively, across Caco-2 cell monolayers, MDCKII/BCRP, and MDCKII/P-gp cells were determined. The results demonstrate that black ginger extract (10 μg/ml) significantly increases 3H-Digoxin and 3H-Estrone sulfate transport from the apical to basolateral side while decreasing transport from the basolateral to apical side of Caco-2 cells and MDCKII cell overexpression of BCRP or P-gp. The effect of the extract on 3H-Digoxin and 3H-Estrone sulfate transport was related to a decrease in efflux ratio. Likewise, DMF (5 μM) significantly increased 3H-Digoxin and 3H-Estrone sulfate absorption with a decreased efflux ratio compared to the control. Interestingly, the extract also significantly increased absorption of paclitaxel, an anti-cancer drug, which has poor oral absorption. Taken together, co-administration of drugs as substrates of BCRP and P-gp, with the black ginger extract containing DMF, might alter the pharmacokinetic profiles of the medicine.

Effects of a locally administered risedronate/autogenous bone graft combination on bone healing in a critical-size rabbit defect model

BackgroundRisedronate is a bisphosphonate with poor oral absorption. An extremely hydrophilic molecule that has a high affinity for bone, risedronate also inhibits the farnesyl diphosphate synthase enzyme, inhibiting osteoclastic activity and reducing bone turnover and resorption. Autogenous bone grafts contain osteogenic cells and osteoinductive factors that are essential for bone regeneration and are therefore considered the gold standard. Thus, this study aimed to investigate the impact of local risedronate administered with autogenous bone grafts on the healing of defects in rabbit skulls using histological, histomorphometric, immunohistochemical, and three-dimensional radiological methods.MethodsTwo 10-mm-diameter critical-size defects were created in 16 rabbits and filled with autogenous bone graft and autogenous bone graft + 5 mg risedronate in the control (C) and risedronate (RIS) groups, respectively. Residual graft, new bone, soft tissue areas, and bone volume were evaluated in the 4- and 8-week study groups.ResultsThere were no statistically significant differences in bone graft, new bone, or soft tissue area between the groups at 4 weeks (p > 0.05). At 8 weeks, the new bone area was significantly higher in the RIS group than in the C group (p < 0.05). The h scores obtained from sialoprotein and osteopontin did not differ significantly between the groups (p > 0.05). The radiologically measured total bone volume was significantly higher in the RIS group than in the C group at both time points (p < 0.05).ConclusionsIn this study, risedronate enhanced the osteoconductive properties of autogenous bone grafts and rapidly created better-quality bone. This could improve future patient outcomes.

Pharmacological Mechanisms and Clinical Applications of Curcumin: Update.

Curcumin, a well-known hydrophobic polyphenol extracted from the rhizomes of turmeric (Curcuma longa L.), has attracted great interest in the last ten years due to its multiple pharmacological activities. A growing body of evidence has manifested that curcumin has extensive pharmacological activities including anti-inflammatory, anti-oxygenation, lipid regulation, antiviral, and anticancer with hypotoxicity and minor adverse reactions. However, the disadvantages of low bioavailability, short half-life in plasma, low drug concentration in blood, and poor oral absorption severely limited the clinical application of curcumin. Pharmaceutical researchers have carried out plenty of dosage form transformations to improve the druggability of curcumin and have achieved remarkable results. Therefore, the objective of this review summarizes the pharmacological research progress, problems in clinical application and the improvement methods of curcumin's druggability. By reviewing the latest research progress of curcumin, we believe that curcumin has a broad clinical application prospect for its wide range of pharmacological activities with few side effects. The deficiencies of lower bioavailability of curcumin could be improved by dosage form transformation. However, curcumin in the clinical application still requires further study regarding the underlying mechanism and clinical trial verification.