ABSTRACT
Cadmium (Cd) is one of non-essential heavy metals which is released into environment naturally or anthropogenically. It is highly persistent toxic metals that are exceptionally distressing industrial and agriculture activities by contaminating soil, water and food. Its long-duration endurance in soil and water results in accumulation and uptake into plants, leading to the food chain. This becomes a serious global problem threatening humans and animals as food chain components. Living organisms, especially humans, are exposed to Cd through plants as one of the main vegetative food sources. This review paper is concentrated on the symptoms of the plants affected by Cd toxicity. The absorption of Cd triggers several seen and unseen symptoms by polluted plants such as stunted growth, chlorosis, necrosis and wilting. Apart from that, factors that affect the uptake and translocation of Cd in plants are elaborated to understand the mechanism that contributes to its accumulation. By insight of Cd accumulation, this review also discussed the phytoremediation techniques-phytoextraction, phytostimulation, phytostabilization, phytovolatization and rhizofiltration in bioremediating the Cd.
O cádmio (Cd) é um dos metais pesados âânão essenciais que é liberado no meio ambiente de forma natural ou antropogênica. São metais tóxicos altamente persistentes que prejudicam excepcionalmente as atividades industriais e agrícolas, contaminando o solo, a água e os alimentos. Sua resistência de longa duração no solo e na água resulta em acúmulo e absorção pelas plantas, levando à cadeia alimentar. Isso se torna um sério problema global que ameaça humanos e animais como componentes da cadeia alimentar. Os organismos vivos, principalmente os humanos, são expostos ao Cd através das plantas como uma das principais fontes de alimento vegetativo. Este artigo de revisão concentra-se nos sintomas das plantas afetadas pela toxicidade do Cd. A absorção de Cd desencadeia vários sintomas visíveis e invisíveis por plantas poluídas, como crescimento atrofiado, clorose, necrose e murcha. Além disso, são elaborados fatores que afetam a absorção e translocação de Cd nas plantas para entender o mecanismo que contribui para o seu acúmulo. A partir do conhecimento do acúmulo de Cd, esta revisão também discutiu as técnicas de fitorremediação - fitoextração, fitoestimulação, fitoestabilização, fitovolatização e rizofiltração na biorremediação do Cd.
Subject(s)
Plants/toxicity , Cadmium , Metals, Heavy , Food/toxicityABSTRACT
Abstract Cadmium (Cd) is one of non-essential heavy metals which is released into environment naturally or anthropogenically. It is highly persistent toxic metals that are exceptionally distressing industrial and agriculture activities by contaminating soil, water and food. Its long-duration endurance in soil and water results in accumulation and uptake into plants, leading to the food chain. This becomes a serious global problem threatening humans and animals as food chain components. Living organisms, especially humans, are exposed to Cd through plants as one of the main vegetative food sources. This review paper is concentrated on the symptoms of the plants affected by Cd toxicity. The absorption of Cd triggers several seen and unseen symptoms by polluted plants such as stunted growth, chlorosis, necrosis and wilting. Apart from that, factors that affect the uptake and translocation of Cd in plants are elaborated to understand the mechanism that contributes to its accumulation. By insight of Cd accumulation, this review also discussed the phytoremediation techniques-phytoextraction, phytostimulation, phytostabilization, phytovolatization and rhizofiltration in bioremediating the Cd.
Resumo O cádmio (Cd) é um dos metais pesados não essenciais que é liberado no meio ambiente de forma natural ou antropogênica. São metais tóxicos altamente persistentes que prejudicam excepcionalmente as atividades industriais e agrícolas, contaminando o solo, a água e os alimentos. Sua resistência de longa duração no solo e na água resulta em acúmulo e absorção pelas plantas, levando à cadeia alimentar. Isso se torna um sério problema global que ameaça humanos e animais como componentes da cadeia alimentar. Os organismos vivos, principalmente os humanos, são expostos ao Cd através das plantas como uma das principais fontes de alimento vegetativo. Este artigo de revisão concentra-se nos sintomas das plantas afetadas pela toxicidade do Cd. A absorção de Cd desencadeia vários sintomas visíveis e invisíveis por plantas poluídas, como crescimento atrofiado, clorose, necrose e murcha. Além disso, são elaborados fatores que afetam a absorção e translocação de Cd nas plantas para entender o mecanismo que contribui para o seu acúmulo. A partir do conhecimento do acúmulo de Cd, esta revisão também discutiu as técnicas de fitorremediação - fitoextração, fitoestimulação, fitoestabilização, fitovolatização e rizofiltração na biorremediação do Cd.
ABSTRACT
Oral administration is the most convenient way of drug delivery， but due to the existence of intestinal barrier， the oral bioavailability of drugs is generally low， especially for drugs with low water solubility， poor permeability and macromolecules. For decades， researchers have demonstrated that nano-delivery system is one of the most effective strategies to solve this problem， but nano-delivery systems have shown limited improvement in the oral bioavailability of drugs. Therefore， researchers have proposed to use transporter-mediated nano-delivery systems to promote the oral absorption of drugs. The intestinal tract were highly expressed as a transporter for ingesting various nutrients（such as glucose， oligopeptides and bile acids）， which was an excellent target of oral drug delivery system. Its substrate were modified on the nano-delivery system， and the loaded drugs could cross the intestinal barrier and enter the systemic circulation more efficiently through the targeting effect of transporters. At present， more and more evidences supported the potential of transporters in the field of oral drug delivery system. Therefore， this paper reviewed the research on intestinal transporters-mediated nano-delivery system to promote oral absorption of drugs， including the distribution of intestinal transporters， three strategies of transporter substrate modification， the transport properties of different types of transporters and their effects of mediating the nano-delivery system for promoting the oral absorption of drugs or treating diseases， with the aim of providing an important theoretical reference for the development of intestinal targeted nano-delivery systems.
ABSTRACT
ObjectiveTo clarify the scientific validity of in vivo pharmacokinetic determination of the whole drug composition in Shenbai nanosuspension in rats， and to provide methodological guidance and theoretical basis for the in vivo study of multi-component complex system of traditional Chinese medicine（TCM） preparations. MethodThe concentration of the overall components， mainly total saponins and total polysaccharides in Shenbai decoction and Shenbai nanosuspension， was determined in rat plasma at different times by area under the absorbance-wavelength curve method（AUAWC）， and the concentration of individual ginsenoside Rg1 was determined by high performance liquid chromatography（HPLC）， and the methodology was verified. The pharmacokinetic parameters of the whole component were compared with those of ginsenoside Rg1 to evaluate the in vivo operational characteristics of the two preparations. ResultThe methodological investigations of AUAWC and HPLC were in accordance with the requirements. AUAWC analysis showed that the overall components in both the decoction group and the nanosuspension group showed a one-compartment model， with half-life（t1/2） of 2.43 h and 2.04 h， respectively. The relative bioavailability of Shenbai nanosuspension was 138.99%. HPLC assay showed that ginsenoside Rg1 in the decoction group and the nanosuspension group showed a two-compartment model， with distribution half-life（t1/2α） of 0.13 h and 2.55 h， and elimination half-life（t1/2β） were 14.28 h and 3.85 h， respectively. The relative bioavailability of Shenbai nanosuspension was 127.49%. Compared with Shenbai decoction， the time to peak（tmax）， peak concentration（Cmax） and area under the drug-time curve（AUC） of the overall components and ginsenoside Rg1 in Shenbai nanosuspension were increased. ConclusionThe established AUAWC can be used for the pharmacokinetic study of the overall components of TCM preparations， which is complementary to the results of individual components measured by HPLC， and can provide useful reference for the in vivo study of new dosage forms of TCM.
ABSTRACT
Buccal tablets
Diclofenac sodium
Drug release
Mucoadhesion
Mucoadhesive tablets
Release kinetics
ABSTRACT
The application of intraocular drug delivery is usually limited due to special anatomical and physiological barriers, and the elimination mechanisms in the eye. Organic nano-drug delivery carriers exhibit excellent adhesion, permeability, targeted modification and controlled release abilities to overcome the obstacles and improve the efficiency of drug delivery and bioavailability. Solid lipid nanoparticles can entrap the active components in the lipid structure to improve the stability of drugs and reduce the production cost. Liposomes can transport hydrophobic or hydrophilic molecules, including small molecules, proteins and nucleic acids. Compared with linear macromolecules, dendrimers have a regular structure and well-defined molecular mass and size, which can precisely control the molecular shape and functional groups. Degradable polymer materials endow nano-delivery systems a variety of size, potential, morphology and other characteristics, which enable controlled release of drugs and are easy to modify with a variety of ligands and functional molecules. Organic biomimetic nanocarriers are highly optimized through evolution of natural particles, showing better biocompatibility and lower toxicity. In this article, we summarize the advantages of organic nanocarriers in overcoming multiple barriers and improving the bioavailability of drugs, and highlight the latest research progresses on the application of organic nanocarriers for treatment of ocular diseases.
Subject(s)
Drug Carriers , Delayed-Action Preparations , Drug Delivery Systems , Nanoparticles/chemistryABSTRACT
This study aims to improve the solubility and bioavailability of daidzein by preparing the β-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940) nanocrystals. Specifically, the nanocrystals were prepared with daidzein as a model drug, PEG_(20000), Carbomer_(940), and NaOH as a plasticizer, a gelling agent, and a crosslinking agent, respectively. A two-step method was employed to prepare the β-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940) nanocystals. First, the insoluble drug daidzein was embedded in β-cyclodextrin to form inclusion complexes, which were then encapsulated in the PEG_(20000)/Carbomer_(940) nanocrystals. The optimal mass fraction of NaOH was determined as 0.8% by the drug release rate, redispersability, SEM morphology, encapsulation rate, and drug loading. The inclusion status of daidzein nanocrystals was determined by Fourier transform infrared spectroscopy(FTIR), thermogravimetric analysis(TGA), and X-ray diffraction(XRD) analysis to verify the feasibility of the preparation. The prepared nanocrystals showed the average Zeta potential of(-30.77±0.15)mV and(-37.47±0.64)mV and the particle sizes of(333.60±3.81)nm and(544.60±7.66)nm before and after daidzein loading, respectively. The irregular distribution of nanocrystals before and after daidzein loading was observed under SEM. The redispersability experiment showed high dispersion efficiency of the nanocrystals. The in vitro dissolution rate of nanocrystals in intestinal fluid was significantly faster than that of daidzein, and followed the first-order drug release kinetic model. XRD, FTIR, and TGA were employed to determine the polycrystalline properties, drug loading, and thermal stability of the nanocrystals before and after drug loading. The nanocrystals loaded with daidzein demonstrated obvious antibacterial effect. The nanocrystals had more significant inhibitory effects on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa than daidzein because of the improved solubility of daidzein. The prepared nanocrystals can significantly increase the dissolution rate and oral bioavailability of the insoluble drug daidzein.
Subject(s)
Sodium Hydroxide , Acrylic Resins , Escherichia coli , NanoparticlesABSTRACT
Objective To evaluate the release characteristics in vitro, pharmacokinetics in rabbits and in vivo-in vitro correlation of silymarin phospholipid complex microporous osmotic pump controlled release tablets（SM-PC MPOP）. Methods The release characteristics of SM-PC MPOP in vitro were detected by HPLC in the artificial gastric fluid. Six beagle dogs were subjected to double cycle cross control, which were given SM-PC MPOP and Legalon（30 mg/kg）. The concentration of silybin in plasma was determined by HPLC and the data were processed by software. Results The cumulative release rate of SM-PC MPOP in vitro was over 85% in 12 h. The pharmacokinetics in beagle dogs showed that SM-PC MPOP and legalon conformed to double compartment first-order absorption model and the pharmacokinetic parameters were obtained: tmax:（3.2±0.4）and（0.9±0.1）h, Cmax:（0.298 6±0.068 9）and（0.629 9±0.076 5）μg/ml, AUC0→24:（2.996 8±0.583 3）and（2.268 9±0.432 8）h·μg /ml. The relative bioavailability of SM-PC MPOP was（162.21 ± 30.82）%. Conclusion SM-PC MPOP could release slowly, which could increase the relative bioavailability significantly. The correlation between the absorption in vivo and release in vitro was fine（r = 0.839 0）.
ABSTRACT
Existe uma associação entre diabetes e a periodontite, e a Metformina (MET) além de controlar os níveis glicêmicos, tem apresentado efeitos antiinflamatórios e na diminuição da perda óssea periodontal. Ao se veicular a MET a um sistema de nanopartículas pode-se apresentar a vantagem de aumento da eficácia terapêutica. Objetivos: esse estudo consistiu na avaliação dos efeitos antiinflamatórios, perda óssea e disponibilidade in vitro/in vivo de uma nanopartícula de ácido poli lático-co-glicólico (PLGA) associada à MET em um modelo de periodontite induzida por ligadura. Materiais e métodos: o PLGA carreado com diferentes doses da MET foi caracterizado pelo seu diâmetro médio, tamanho da partícula, índice de polidispensão e eficiência de aprisionamento. Foram utilizados ratos machos da linhagem Wistar, divididos aleatoriamente, em grupos controles e experimentais com diferentes doses de MET associadas ou não ao PLGA, os quais receberam diferentes tratamentos. Amostras de maxilas e tecidos gengivais foram utilizadas para avaliação de perda óssea e inflamação, por meio da microtomografia computadorizada, histopatológico, imunohistoquímica, análise de citocinas inflamatórias e expressão gênica de proteínas por RT-PCR quantitativo. Para o ensaio de liberação in vitro, utilizou-se o dispositivo de células de difusão vertical de Franz estáticas. Para a disponibilidade in vivo, as amostras de sangue foram coletadas em diferentes intervalos de tempo e analisadas por cromatografia líquida de alta eficiência acoplado a espectrometria de massas (HPLC-MS/MS). Resultados: o diâmetro médio das nanopartículas de PLGA carreadas com MET estava em um intervalo de 457,1 ± 48,9 nm (p <0,05) com um índice de polidispersidade de 0,285 (p <0,05), potencial Z de 8,16 ± 1,1 mV (p <0,01) e eficiência de aprisionamento (EE) de 66,7 ± 3,73. O tratamento com a MET 10 mg / kg + PLGA mostrou uma baixa concentração de células inflamatórias, fraca imunomarcação para RANKL, Catepsina K, OPG e osteocalcina. Diminuição dos níveis de IL-1ß e TNF-α (p <0,05), aumento da expressão gênica do AMPK (p <0,05) e diminuição do NF-κB p65, HMGB1 e TAK-1 (p <0,05). O 10 mg/kg MET + PLGA foi liberado no ensaio in vitro sugerindo um modelo cinético de difusão parabólica com um perfil de liberação que atinge 50% de seu conteúdo em 2h e permanece em liberação constante em torno de 60% até o final de 6h. O ensaio in vivo mostrou o volume aparente de distribuição Vz/F (10 mg/kg MET + PLGA, 46,31 mL/kg vs. 100 mg/kg MET + PLGA, 28,8 mL/kg) e o tempo médio de residência MRTinf (PLGA + MET 10 mg /kg, 37,66h vs. MET 100 mg/kg, 3,34h). Conclusão: o PLGA carreado com MET diminuiu a inflamação e a perda óssea na periodontite em ratos diabéticos. O 10 mg/kg MET + PLGA teve uma taxa de eliminação mais lenta em comparação com o MET 100 mg/kg. A formulação modifica os parâmetros farmacocinéticos, como volume de distribuição aparente e tempo médio de residência (AU).
There is an association between diabetes and periodontitis, and Metformin (MET) in addition to controlling glycemic levels, has shown anti-inflammatory effects and decreased periodontal bone loss. By transferring MET to a nanoparticle system, the advantage of increasing therapeutic efficacy can be presented. Objectives: this study consisted of evaluating the antiinflammatory effects, bone loss and in vitro/in vivo availability of a polylactic-co-glycolic acid (PLGA) nanoparticle associated with MET in a ligature-induced periodontitis model. Materials and methods: PLGA loaded with different doses of MET was characterized by its mean diameter, particle size, polydispension index and entrapment efficiency. Male Wistar rats were used, randomly divided into control and experimental groups with different doses of MET associated or not with PLGA, which received different treatments. Samples of jaws and gingival tissues were used to assess bone loss and inflammation, using computed microtomography, histopathology, immunohistochemistry, analysis of inflammatory cytokines and gene expression of proteins by quantitative RT-PCR. For the in vitro release assay, the static Franz vertical diffusion cell device was used. For in vivo availability, blood samples were collected at different time intervals and analyzed by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS). Results: the mean diameter of MET-loaded PLGA nanoparticles was in the range of 457.1 ± 48.9 nm (p <0.05) with a polydispersity index of 0.285 (p <0.05), Z potential of 8.16 ± 1.1 mV (p <0.01) and trapping efficiency (EE) of 66.7 ± 3.73. Treatment with MET 10 mg/kg + PLGA showed a low concentration of inflammatory cells, weak immunostaining for RANKL, Cathepsin K, OPG and osteocalcin. Decreased IL-1ß and TNF-α levels (p <0.05), increased AMPK gene expression (p <0.05) and decreased NF-κB p65, HMGB1 and TAK-1 (p <0. 05). The 10 mg/kg MET + PLGA was released in the in vitro assay suggesting a kinetic model of parabolic diffusion with a release profile that reaches 50% of its content in 2h and remains in constant release around 60% until the end of 6h . The in vivo assay showed the apparent volume of distribution Vz/F (10 mg/kg MET + PLGA, 46.31 mL/kg vs. 100 mg/kg MET + PLGA, 28.8 mL/kg) and the mean MRTinf residency (PLGA + MET 10 mg/kg, 37.66h vs. MET 100 mg/kg, 3.34h). Conclusion: MET-loaded PLGA decreased inflammation and bone loss in periodontitis in diabetic rats. 10 mg/kg MET + PLGA had a slower rate of elimination compared to 100 mg/kg MET. The formulation modifies pharmacokinetic parameters such as apparent volume of distribution and mean residence time (AU).
Subject(s)
Animals , Rats , Periodontal Diseases/therapy , Polylactic Acid-Polyglycolic Acid Copolymer/adverse effects , Metformin/adverse effects , In Vitro Techniques/methods , Biological Availability , Analysis of Variance , Rats, Wistar , Hypoglycemic Agents/adverse effects , Anti-Inflammatory Agents/adverse effectsABSTRACT
Rasasastra is a specialised branch of Ayurveda that deals with Rasa dravyas which include Visha dravyas used for the preparation of therapeutically potent medicines. Agnikumara rasa of Bhaishajya Ratnavali Jwara adhikara reference is one such herbal formulation that contains a major proportion of Shodhita Vatsanabha and other ingredients of Maricha, Vacha, Kushta, Mushta, and Ardraka. It is a Kharaliya yoga (a formulation prepared in mortar) prepared by Bhavana samskara (levigation). As the number of levigation is not mentioned, three samples were prepared by doubling the number of Bhavana (levigation) of the preceding sample and physico-chemical analysis of these samples was done and compared. In Charaka samhita Vimanasthana, Acharya has explained the relevance of Samskara for imparting new Gunas (properties) and thereby potentiating the drug. The present study was done to identify a better analytical profile among the samples. It was found that some of the analytical parameters like hardness, disintegration time were modified with Bhavana which may increase the bioavailability of the drug and thereby its therapeutic potency
ABSTRACT
This study aims to analyze the AntiCovid effect of Phytocompounds extracted from Native Indian Plant species by computational methods such as Molecular Docking. Through this study keeping the Indian Heritage alive we characterized the ability of these phytochemicals as inhibiting agents of the Main Protease enzyme of this Virus. The lack of any effective treatment and the reoccurrence of cases despite Vaccination necessitates the quick provision of anti-SARS-CoV-2 drugs. Natural substances are getting a lot of attention for SARS-CoV-2 therapy as they have proven antimicrobial activities and are a key source for numerous antiviral drugs. Despite the fact that this virus has several identified target receptors, Main Protease (Mpro) is crucial for viral replication. In this study, 26 phytochemicals from 10 native Indian plant species were studied. Our docking studies demonstrated that compounds Quercetin, Withaferin A, Sominone, and Nimbin were likely to be more favorable than the natural inhibitor N3, with binding energies of?8.42, ?9.21, ?9.95, and ?8.88 kcal/mol, respectively. These four candidate natural compounds were further examined for their bioavailability scoresthrough ADMET analysis to prove the safety of these compounds as well as their drug likeliness.Through the results it was indicated that these natural phytochemicals have a significant potential of inhibiting the SARS-CoV-2 Mpro enzyme and might be utilized to treat SARS-CoV-2 and manage public health, subject to in vitro validation in the future.
ABSTRACT
Resumen Introducción: el objetivo del presente trabajo se centra en reconocer la importancia de las investigaciones que relacionan la biodisponibilidad de fósforo en diferentes grupos de alimentos de origen animal, vegetal e industrial y su efecto en la progresión de la enfermedad renal crónica (ERC). Metodología: la revisión se sustentó en la búsqueda literaria en páginas web como PUBMED, Redalyc, SciELO, SCIHUB y Google Academic. Se seleccionó cada estudio, descartando aquellos que no fueran cuantitativos u originales, estuvieran incompletos, sin metodología clara, realizados en mamíferos o si los resultados no se especificaban en porcentajes. La lectura puso especial énfasis en el índice de biodisponibilidad de fósforo derivado del consumo de distintos productos alimenticios. Se elaboraron tres matrices de acuerdo con el origen del comestible y la biodisponibilidad de fósforo que absorbe el organismo. Resultados: se encontró que los alimentos industrializados y los aditivos muestran una biodisponibilidad de fósforo del 90 % al 100 %, los de origen animal del 40 % al 80 % y los de origen vegetal del 30 %. Conclusiones: los aditivos de los alimentos industrializados promueven la hiperfosfatemia y, con ello, aceleran la progresión de la enfermedad renal crónica, a diferencia de los de origen animal y vegetal, menos perjudiciales para la salud. Esto da pauta a la formación del sector salud para ampliar su conocimiento sobre el tratamiento nutricional del paciente.
Abstract Introduction: to know the importance of the investigations that relate the bioavailability of phosphorus in different groups of foods of animal, vegetable and industrialized origin and its effect on the progression in patients with Chronic Kidney Disease (CKD). Methodology: the review is based on a literary search that was carried out on web pages such as: PUBMED, Redalyc, SciELO, SCIHUB and Google Academic. Each of the studies was selected discarding those that were not quantitative, original, complete, with clear methodology, carried out in mammals, and that in their results specified the bioavailability of phosphorus in percentages. All the studies were read, placing main emphasis and interest on the percentage of phosphorus bioavailability when consuming different food groups. Three matrices were made according to the origin of the food and the bioavailability of phosphorus that is absorbed in the body; grouping them into foods of animal, vegetable and industrialized origin and additives. Results: it was found that industrialized foods and additives show a phosphorus bioavailability of 90-100%, those of animal origin 40-80%, those of plant origin 30%. Conclusions: The additives used in industrialized foods promote hyperphosphatemia and thus accelerate the progression of chronic kidney disease, unlike foods of animal and vegetable origin that are less harmful to health. This guides the training of the health sector, expanding its knowledge in the nutritional treatment of the patient.
Subject(s)
Humans , Phosphorus , Biological Availability , Renal Insufficiency, Chronic , Food , Food AdditivesABSTRACT
This study evaluated the specific interactions between drug and polymers in amorphous spray dried dispersions (SDDs). Four Biopharmaceutics Classification System (BCS) II class drugs were evaluated. Binary and ternary SDDs were manufactured with conventional polymers and arabinogalactan. Specific interaction parameters between drug and polymer were determined using theoretical calculations and DSC data. Analytical methods were used to evaluate solid and solution state interactions. Maximum amorphous content for each formulation was calculated using DSC. Flory-Huggins Specific Interaction Parameters were calculated. Negative specific parameters were associated with solid-state interactions and improved capacity of drug in the amorphous state. Ternary SDDs containing drug, polymer, and arabinogalactan displayed similar hydrogen bonding as was observed with binary SDDs. Solution-state interactions observed in binary systems may be used in tertiary systems to improve the amorphous drug capacity and improved dissolution compared to the binary. The resultant tertiary systems are an improvement over binary drug polymer systems.
Este estudio evaluó las interacciones específicas entre el fármaco y los polímeros en dispersiones amorfas secadas por pulverización (SDD). Se evaluaron cuatro fármacos de clase II del Sistema de Clasificación Biofarmacéutica (BCS). Los SDD binarios y ternarios se fabricaron con polímeros convencionales y arabinogalactano. Los parámetros de interacción específicos entre el fármaco y el polímero se determinaron utilizando cálculos teóricos y datos de DSC. Se utilizaron métodos analíticos para evaluar las interacciones del estado sólido y de la solución. El contenido amorfo máximo para cada formulación se calculó usando DSC. Se calcularon los parámetros de interacción específicos de Flory-Huggins. Los parámetros específicos negativos se asociaron con interacciones en estado sólido y una capacidad mejorada del fármaco en el estado amorfo. Los SDD ternarios que contienen fármaco, polímero y arabinogalactano mostraron enlaces de hidrógeno similares a los observados con los SDD binarios. Las interacciones de estado de solución observadas en sistemas binarios pueden usarse en sistemas terciarios para mejorar la capacidad del fármaco amorfo y mejorar la disolución en comparación con el binario. Los sistemas terciarios resultantes son una mejora con respecto a los sistemas de polímeros de fármacos binarios.
Subject(s)
Polymers/chemistry , Solubility , Pharmaceutical Preparations/chemistry , Biological Availability , Temperature , X-Ray Diffraction , Microscopy, Electron, Scanning , Spectroscopy, Fourier Transform Infrared , Proton Magnetic Resonance SpectroscopyABSTRACT
Berberine(BBR),an isoquinoline alkaloid,has been found in many plants,such as Coptis chinensis Franch and Phellodendron chinense Schneid.Although BBR has a wide spectrum of pharmacological effects,its oral bioavailability is extremely low.In recent years,gut microbiota has emerged as a cynosure to un-derstand the mechanisms of action of herbal compounds.Numerous studies have demonstrated that due to its low bioavailability,BBR can interact with the gut microbiota,thereby exhibiting altered pharma-cological effects.However,no systematic and comprehensive review has summarized these interactions and their corresponding influences on pharmacological effects.Here,we describe the direct interactive relationships between BBR and gut microbiota,including regulation of gut microbiota composition and metabolism by BBR and metabolization of BBR by gut microbiota.In addition,the complex interactions between gut microbiota and BBR as well as the side effects and personalized use of BBR are discussed.Furthermore,we provide our viewpoint on future research directions regarding BBR and gut microbiota.This review not only helps to explain the mechanisms underlying BBR activity but also provides support for the rational use of BBR in clinical practice.
ABSTRACT
Abstract Pharmacokinetic studies were carried out in male and female rats to quantify silymarin as silybin (A+B) after the oral administration of various silymarin formulations combined with three bioenhancers, namely, lysergol, piperine, and fulvic acid, and compared with plain silymarin formulation (control). A non-compartmental analysis, model independent analysis, was utilized, and various pharmacokinetic parameters (C max, T max, and AUC 0-t) were calculated individually for each treatment group, and the values were expressed as mean ± SEM (n = 6). Plasma samples obtained from the rats were analyzed for the concentration of silymarin through a validated RP-HPLC method and on the basis of data generated from the pharmacokinetic studies. Results indicated that the bioenhancers augmented pharmacokinetic parameters and bioavailability increased 2.4-14.5-fold in all the formulations compared with the control. The current work envisages the development of an industrially viable product that can be further subjected to clinical trials and scientifically supports the development of silymarin as a contemporary therapeutic agent with enhanced bioavailability and medicinal values.
Subject(s)
Animals , Male , Female , Rats , Silymarin/analysis , Silymarin/agonists , Acids/adverse effects , Biological Availability , Administration, Oral , Chromatography, High Pressure Liquid/methodsABSTRACT
Cambuci (Campomanesia phaea Berg) is a native fruit of the Atlantic Coastal Forest, belonging to the Myrtaceae family, rich in ellagitannins (ET), proanthocyanidins and other bioactive phenolic compounds (BPCs) related to beneficial effects to human health, such as systemic inflammation and attenuation of insulin resistance. Evidence indicates that the beneficial effects of some BPCs, such as ellagitannins, are associated to their chronic intake and the action of the metabolites produced. Urolithins are the main metabolites produced after consumption from a rich source of ellagitannins. According to the metabolite produced, subjects can be classified into metabotypes (A, B e 0). However, nothing is known about the uptake and metabolism of BPC from cambuci. Thus, the objectives of this study were the physical-chemical characterization of cambuci pulp, identification of BPC profile and the determination of their bioavailability in healthy and overweight/obese subjects. Therefore, subjects (n = 28, being 15 healthy and 13 overweight/obese) consumed cambuci juice, and their respective urines 24 hours after drinking were collected to identify the metabolites of ellagitannins. Cambuci presented high acidity, with pH values of ~ 2.3 and titratable acidity of ~ 1.9 g citric acid equivalents/100 g fresh weight (FW), and solids content of ~7.5 ° Brix, not being characterized as a very sweet fruit. The total phenolic content was ~ 780 mg gallic acid/100 mL juice. The total amount of flavan-3-ols found in the fruit was 45.45 g/kg dry weight (DW) and the main monomers identified were gallocatechin (22.25 g/kg DW) and epigallocatechin gallate (16.48 g/kg DW). The degree of polymerization of flavan3-ol was 32.78, indicating a high intensity of astringency and low bioavailability. Through LC-MS, 26 BPCs were identified, most of them being derived from ellagitannins, and among those identified, telemagrandin II and, pedunculagin. The total ellagic acid content found was ~6.2 mg/g DW, demonstrating that cambuci is a fruit rich in ellagic acid and its derivatives. The 28 volunteers who consumed cambuci juice for the bioavailability assessment were classified, for the first time, into metabotypes according to the type of urolithin produced. Metabotype A was the most prevalent (64.3%), followed by metabotype B (17.9%) and 0 (17.9%). When analyzed according to nutritional status, metabotype A was prevalent in both groups. In conclusion, the BCP profile of cambuci stands out for the presence of ET, such as telemagrandin II and pedunculagin. Due to the high degree of polymerization, no proanthocyanidin metabolites were observed. Metabotype A was the most prevalent in this study population, and nutritional status may not be a determining factor in the type of urolithin produced
O cambuci (Campomanesia phaea Berg), é um fruto nativo da mata Atlântica, pertencente à família das mirtáceas, rico em elagitaninos (ET), proantocianidinas e outros compostos bioativos fenólicos (CBF) que estão associados a vários efeitos biológicos benéficos à saúde humana, tais como atenuação inflamação sistêmica e da resistência à insulina. Evidências apontam que os efeitos benéficos de alguns CBF, como os elagitaninos, estão associados com sua ingestão crônica e à ação dos metabólitos produzidos. As urolitinas são os principais metabólitos produzidos após o consumo de uma fonte rica em elagitaninos. De acordo com o metabólito produzido, os indivíduos podem ser classificados em metabotipos (A, B e 0). No entanto, nada se sabe sobre a absorção e a metabolização dos CBF do cambuci. Desta forma, os objetivos deste trabalho foram a caracterização físico-química da polpa de cambuci, a identificação dos CBF e a avaliação da biodisponibilidade dos polifenóis presentes no suco deste fruto, em seres humanos saudáveis e com sobrepeso/obesidade. Para tanto, os voluntários (n = 28, sendo 15 saudáveis e 13 obesos) consumiram suco de cambuci, e suas respectivas urinas 24 horas, após a ingestão da bebida, foram coletadas para identificação dos metabólitos de elagitaninos. O cambuci apresentou uma alta acidez, com valores de pH de ~2,3 e acidez total titulável de ~1,9 g equivalentes de ácido cítrico/100 g em base úmida (b.u.), e teor de sólidos solúveis de ~7,5 ºBrix, não sendo, portanto, muito ácido. O teor de fenólicos totais encontrado foi ~ 780 mg equivalentes de ácido gálico/100 mL de suco. A quantidade total de flavan-3-ois encontrada na polpa de cambuci foi de 45,45 g/kg em base seca (b.s.) e os principais monômeros identificados foram a galocatequina (22,25 g/kg b.s.) e a epigalocatequina galato (16,48 g/kg b.s.). O grau de polimerização do flavan-3-ol foi de 32,78 indicando uma alta intensidade de adstringência e baixa biodisponibilidade. Através de LCMS foi feita a identificação de 26 CBF, sendo sua grande maioria derivados de elagitaninos, e dentre os identificados podemos destacar telemagrandina II e pedunculagina. O teor de elagitaninos encontrado foi de ~6,2 mg/g (b.s.), demonstrando que o cambuci é um fruto rico em ácido elágico e seus derivados. Os 28 voluntários que consumiram o suco de cambuci para ensaio de biodisponibilidade foram classificados, pela primeira vez, em metabotipos de acordo com o tipo de urolitina produzida. O metabotipo A foi o mais prevalente (64,3%), seguido pelo metabotipo B (17,9%) e 0 (17,9%). Quando analisados de acordo com o estado nutricional, o metabotipo A foi prevalente em ambos os grupos. Conclui-se, portanto, que o perfil de CBF do cambuci se destaca pela presença de ET, tais como telimagrandina II e pedunculagina. Devido ao alto grau de polimerização não foram observados metabólitos de proantocianidinas. O metabotipo A foi o mais prevalente na população deste estudo, e o estado nutricional pode não ser um fator determinante no tipo de urolitina produzida
Subject(s)
Myrtaceae/adverse effects , Fruit/classification , Obesity/pathology , Insulin Resistance , Chemistry, Physical , Phenolic CompoundsABSTRACT
Abstract Tadalafil (Tad) is a poorly water-soluble drug (BCS class II) that is used for the treatment of erectile dysfunction. An enhancement of aqueous solubility is vital to accelerate its onset of action and subsequently enhance its therapeutic effect. Binary and ternary mixtures of Tad with different amino acids (histidine, valine, alanine or arginine) and other excipients (mannitol and SLS) were prepared and then spray dried. The solubilizing efficiency and physicochemical characterization of all spray dried mixtures of Tad were studied. The optimum formulation was investigated in male rats to determine the onset of erection and the pharmacokinetic parameters of Tad. In general terms, the drug solubility of spray-dried formulae was enhanced compared to the crystalline form of the drug as a result of the formation of co-amorphous structures. The final result revealed that the Tad/alanine/mannitol spray-dried mixture (F10) showed the highest solubility and an improvement in its physicochemical characteristics. Moreover, F10 showed a significantly faster erection in rats with an improvement in Tad pharmacokinetic parameters when compared to the crystalline drug. Thus, F10 is selected as a promising formulation that successfully enhanced the bioavailability and the therapeutic efficacy of Tad.
Subject(s)
Solubility , Tadalafil/analysis , Pharmaceutical Preparations/analysis , Erectile Dysfunction/pathologyABSTRACT
Abstract As one of the most promising formulations for poorly water-soluble drugs, nanocrystals have been attracting increasing attention in recent years. Isoliquiritigenin (ISL) is a flavonoid with a chalcone structure, and possesses many biological activities. However, its clinical application is significantly limited mainly due to its low oral bioavailability caused by poor hydrophilicity. To address this, ISL nanocrystals were developed in this study to improve its oral bioavailability. Three types of nanocrystals with differing particle size; R1, R2, and R3, were prepared by anti- solvent precipitation or anti-solvent precipitation combined with sonication, which was optimized by single-factor experiments. These nanocrystals were characterized based on their physical properties, in vitro release, and in vivo absorption performance. The mean particle size of R1, R2, and R3 was 555.7, 271.0, and 46.2, respectively. The dissolution ratio of ISL in the nanocrystals was significantly improved, with the quickest rate recorded in R2. Peak concentration and area under the concentration-time curve of R2 after oral administration in rats was 5.83- and 2.72-fold higher than that of the ISL solution, respectively. These findings indicate that the dissolution and absorption of ISL can be significantly enhanced by nanocrystals, and the dissolution behavior and pharmacokinetic properties of nanocrystals is significantly influenced by particle size.
ABSTRACT
Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C18 col-umn(4.6 mm×50 mm,5 μm)under gradient conditions with eluents of methanol:acetonitrile(1∶1,V/V)and 5mM ammonium formate:methanol(9∶1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30 → 437.30 for RA and m/z 256.10 → 227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40 mg/kg)and intravenous(10 mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20 mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1％to 19.4％.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.
ABSTRACT
Anemoside B4 (B4), a main triterpenoid saponin from a traditional Chinese medicine plant, Pulsatilla chinensis, is a novel anti-inflammatory agent for protection from acute lung injury. We investigated the pulmonary availability and anti-inflammatory efficacy of B4 after intratracheal and intravenous dosing with a view to evaluating the suitability of inhalation delivery. All animal studies were performed under the guidelines approved by the Animal Care and Use Committee of Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences (Approval No: SLXD-20181113046). In vitro evaluation of the aerodynamic characteristics and droplet size distribution showed that the aerosols generated by a commercially available nebulizer were well deposited in the respiratory tract. Following intratracheal administration, B4 underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 103%. Compared to intravenous delivery, intratracheal administration dramatically increased the drug availability in lung tissue of rats by more than 1 000-fold, leading to improved and prolonged concentrations of B4 in lung tissue up to 48 h. In addition, the intratracheal administration of B4 resulted in dose-dependent and prolonged anti-inflammatory efficacy in a lipopolysaccharide (LPS)-induced lung injury model in mice. The present results demonstrate that inhalation delivery of B4 is a promising approach to treat pulmonary inflammation with once-daily dosing.