Nanoformulation Development to Improve the Biopharmaceutical Properties of Fisetin Using Design of Experiment Approach.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu WY
PROVIDER: S-EPMC8160650 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Like other organs, brain functions diminish with age. Furthermore, for a variety of neurological disorders-including Alzheimer's disease-age is one of the higher-risk factors. Since in many Western countries the average age is increasing, determining approaches for decreasing the effects of aging on brain function is taking on a new urgency. Neuroinflammation and oxidative stress are two convoluted key factors in brain aging and chronic neurodegenerative diseases. The diverseness of factors, causing an age-related decrease in brain functions, requires identifying small molecules that have multiple biological activities that can affect all these factors. One great source of these small molecules is related to polyphenolic flavonoids. Recently, 3,3',4',7-tetrahydroxyflavone (fisetin) has been reported as a potent senotherapeutic capable of extending lifespan by reducing peroxidation levels and enhancing antioxidant cell responses. The neuroprotective effects of fisetin have been shown in several in vitro and in vivo models of neurological disorders due to its actions on multiple pathways associated with different neurological disorders. The present work aims to collect the most recent achievements related to the antioxidant and neuroprotective effects of fisetin. Moreover, in silico pharmacokinetics, pharmacodynamics, and toxicity of fisetin are also comprehensively described along with emerging novel drug delivery strategies for the amelioration of this flavonol bioavailability and chemical stability.
| S-EPMC8839434 | biostudies-literature
Project description:MotivationSystems biology employs mathematical modelling to further our understanding of biochemical pathways. Since the amount of experimental data on which the models are parameterized is often limited, these models exhibit large uncertainty in both parameters and predictions. Statistical methods can be used to select experiments that will reduce such uncertainty in an optimal manner. However, existing methods for optimal experiment design (OED) rely on assumptions that are inappropriate when data are scarce considering model complexity.ResultsWe have developed a novel method to perform OED for models that cope with large parameter uncertainty. We employ a Bayesian approach involving importance sampling of the posterior predictive distribution to predict the efficacy of a new measurement at reducing the uncertainty of a selected prediction. We demonstrate the method by applying it to a case where we show that specific combinations of experiments result in more precise predictions.Availability and implementationSource code is available at: http://bmi.bmt.tue.nl/sysbio/software/pua.html.
| S-EPMC3324513 | biostudies-literature
Project description:Since its introduction in 1982, biopharmaceutical drugs have revolutionized the treatment of a broad spectrum of diseases and are increasingly used in nearly all branches of medicine. In recent years, the biopharmaceuticals market has developed much faster than the market for all drugs and is believed to have great potential for further dynamic growth because of the tremendous demand for these drugs. Biobetters, which contain altered active pharmaceutical ingredients with enhanced efficacy, will play an important role in the development of biopharmaceuticals. Another significant group of biopharmaceuticals are biosimilars. Their introduction in the European Union and, recently, the Unites States markets will reduce the costs of biopharmaceutical treatment. This review highlights recent progress in the field of biopharmaceutical development and issues concerning the registration of innovative biopharmaceuticals and biosimilars. The leading class of biopharmaceuticals, the current biopharmaceuticals market, and forecasts are also discussed.
| S-EPMC6749944 | biostudies-literature
Project description:The purpose of the present study was to formulate polymeric self-emulsifying curcumin nanocapsules with high encapsulation efficiency, good emulsification ability, and optimal globule size for localized targeting in the colon. Formulations were prepared using modified quasiemulsion solvent diffusion method. Concentration of formulation variables, namely, X1 (oil), X2 (polymeric emulsifier), and X3 (adsorbent), was optimized by design of experiments using Box-Behnken design, for its impact on mean globule size (Y1) and encapsulation efficiency (Y2) of the formulation. Polymeric nanocapsules with an average diameter of 100-180?nm and an encapsulation efficiency of 64.85±0.12% were obtained. In vitro studies revealed that formulations released the drug after 5?h lag time corresponding to the time to reach the colonic region. Pronounced localized action was inferred from the plasma concentration profile (C max 200?ng/mL) that depicts limited systemic absorption. Roentgenography study confirms the localized presence of carrier (0-2?h in upper GIT; 2-4?h in small intestine; and 4-24?h in the lower intestine). Optimized formulation showed significantly higher cytotoxicity (IC50 value 20.32??M) in HT 29 colonic cancer cell line. The present study demonstrates systematic development of polymeric self-emulsifying nanocapsule formulation of curcumin for localized targeting in colon.
| S-EPMC4265377 | biostudies-literature
Project description:Electrospinning is increasingly becoming a viable means of producing drug delivery vehicles for oral delivery, particularly as issues of manufacturing scalability are being addressed. In this study, electrospinning is explored as a taste-masking manufacturing technology for bitter drugs. The taste-masking polymer Eudragit E PO (E-EPO) was electrospun, guided by a quality by design approach. Using a design of experiment, factors influencing the production of smooth fibers were investigated. Polymer concentration, solvent composition, applied voltage, flow rate, and gap distance were the parameters examined. Of these, polymer concentration was shown to be the only statistically significant factor within the ranges studied ( p-value = 0.0042). As the concentration increased, smoother fibers were formed, coupled with an increase in fiber diameter. E-EPO (35% w/v) was identified as the optimum concentration for smooth fiber production. The optimized processing conditions identified were a gap distance of 175 mm, an applied voltage of between 15 and 20 kV, and a flow rate of 1 mL/h. Using this knowledge, the production optimization of electrospun E-EPO with chlorpheniramine maleate (CPM), a bitter antihistamine drug, was explored. The addition of CPM in drug loads of 1:6 up to 1:10 CPM/E-EPO yielded smooth fibers that were electrospun under conditions similar to placebo fibers. Solid-state characterization showed CPM to be molecularly dispersed in E-EPO. An electronic tasting system, or E-tongue, indicated good taste-masking performance as compared to the equivalent physical mixtures. This study therefore describes a means of producing, optimizing, and assessing the performance of electrospun taste-masked fibers as a novel approach to the formulation of CPM and potentially other bitter drug substances.
| S-EPMC6549214 | biostudies-literature
Project description:Hydrophobic drug release from poly (lactic-co-glycolic acid) (PLGA) microspheres typically exhibits a tri-phasic profile with a burst release phase followed by a lag phase and a secondary release phase. High burst release can be associated with adverse effects and the efficacy of the formulation cannot be ensured during a long lag phase. Accordingly, the development of a long-acting microsphere product requires optimization of all drug release phases. The purpose of the current study was to investigate whether a blend of low and high molecular weight polymers can be used to reduce the burst release and eliminate/minimize the lag phase. A single emulsion solvent evaporation method was used to prepare microspheres using blends of two PLGA polymers (PLGA5050 (25 kDa) and PLGA9010 (113 kDa)). A central composite design approach was applied to investigate the effect of formulation composition on dexamethasone release from these microspheres. Mathematical models obtained from this design of experiments study were utilized to generate a design space with maximized microsphere drug loading and reduced burst release. Specifically, a drug loading close to 15% can be achieved and a burst release less than 10% when a composition of 80% PLGA9010 and 90 mg of dexamethasone is used. In order to better describe the lag phase, a heat map was generated based on dexamethasone release from the PLGA microsphere/PVA hydrogel composite coatings. Using the heat map an optimized formulation with minimum lag phase was selected. The microspheres were also characterized for particle size/size distribution, thermal properties and morphology. The particle size was demonstrated to be related to the polymer concentration and the ratio of the two polymers but not to the dexamethasone concentration.
| S-EPMC4609624 | biostudies-literature
Project description:A solvate cocrystal of the antimicrobial norfloxacin (NFX) was formed by using isonicotinamide (INA) as a coformer with the solvent evaporation technique. The cocrystal formation was confirmed by performing solid-state characterization techniques. We evaluated the dissolution under supersaturated conditions and also the solubility at the vertex of triphasic domain of cocrystal and NFX in both water and Fasted-State Simulated Intestinal Fluid (FaSSIF). The antimicrobial activity was evaluated using the microdilution technique. The cocrystal showed 1.8 times higher dissolution than NFX in water at 60 min and 1.3 times higher in FaSSIF at 180 min in the kinetic study. The cocrystal also had an increase in solubility of 8.38 times in water and 6.41 times in FaSSIF. The biopharmaceutical properties of NFX with cocrystallization improved antimicrobial action, as shown in the results of minimum inhibitory concentration (MIC) and inhibitory concentrations of 50% (IC50%) and 90% (IC90%). This paper presents, for the first time, a more in-depth analysis of the cocrystal of NFX-INA concerning its dissolution, solubility, and antimicrobial activity. In all these criteria, the cocrystal obtained better results compared to the pure drug.
| S-EPMC10536922 | biostudies-literature
Project description:Sensitivity is one of the most important parameters to put in the foreground in all sensing applications. Its increase is therefore an ongoing challenge, particularly for surface acoustic wave (SAW) sensors. Herein, finite element method (FEM) simulation using COMSOL Multiphysics software is first used to simulate the physical and electrical properties of SAW delay line. Results indicate that 2D configuration permits to accurately obtain all pertinent parameters, as in 3D simulation, with very substantial time saving. A good agreement between calculation and experiment, in terms of transfer functions (S21 spectra), was also shown to evaluate the dependence of the SAW sensors sensitivity on the operating frequency; 2D simulations have been conducted on 104 MHz and 208 MHz delay lines, coated with a polyisobutylene (PIB) as sensitive layer to dichloromethane (DCM). A fourfold increase in sensitivity was obtained by doubling frequency. Both sensors were then realized and tested as chem-sensors to detect zinc ions in liquid media. 9-{[4-({[4-(9anthrylmethoxy)phenyl]sulfanyl} methyl)]methyl] anthracene (TDP-AN) was selected as the sensing layer. Results show a comparable response curves for both designed sensors, in terms of limit of detection and dissociation constants Kd values. On the other hand, experimental sensitivity values were of the order of [7.0 ± 2.8] × 108 [°/M] and [16.0 ± 7.6] × 108 [°/M] for 104 MHz and 208 MHz sensors, respectively, confirming that the sensitivity increases with frequency.
| S-EPMC7506909 | biostudies-literature
Project description:The physical properties of nanoparticles may affect the uptake mechanism, biodistribution, stability, and other physicochemical properties of drug delivery systems. This study aimed to first develop a model exploring the factors controlling the nanogel physical properties using a single drug (propranolol), followed by an evaluation of whether these models can be applied more generally to a range of drugs. Size, polydispersity, ζ potential, and encapsulation efficiency were investigated using a design of experiment (DOE) approach to optimize formulations by systematically identifying the effects of, and interactions between, parameters associated with nanogel formulation and drug loading. Three formulation factors were selected, namely, chitosan concentration, the ratio between the chitosan and cross-linker─sodium triphosphate─and the ratio between the chitosan and drug. The results indicate that the DOE approach can be used not only to model but also to predict the size and polydispersity index (PDI). To explore the application of these prediction models with other drugs and to identify the relationship between the drug structure and nanogel properties, nanogels loaded with 12 structurally distinct drugs and 6 structurally similar drugs were fabricated at the optimal condition for propranolol in the model. The measured size, PDI, and ζ potential of the nanogels could not be modeled using distinct DOE parameters for dissimilar drugs, indicating that each drug requires a separate analysis. Nevertheless, for drugs with structural similarities, various linear and nonlinear trends were observed in the size, PDI, and ζ potential of nanogels against selected molecular descriptors, indicating that there are indeed relationships between the drug molecular structure and the performance outcomes, which may be modeled and predicted using the DOE approach. In conclusion, the study demonstrates that DOE models can be applied to model and predict the influence of formulation and drug loading on key performance parameters. While distinct models are required for structurally unrelated drugs, it was possible to establish correlations for the drug series investigated, which were based on polarity, hydrophobicity, and polarizability, thereby elucidating the importance of the interactions between the drug and the nanogels based on the nanogel properties and thus deepening the understanding of the drug-loading mechanisms in nanogels.
| S-EPMC9097514 | biostudies-literature
Project description:This article presents data related to the research article "Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain" (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016) [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA)-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs) after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1) Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2) the use of a design of Experiment (DOE) approach (M.W. 2 Weible and T. Chan-Ling, 2007) [2] to select multi-factorial experimental conditions, and (3) Inflammatory response and cell survival after transplantation.
| S-EPMC5154973 | biostudies-literature