Search Results (41)

Background/Objectives: In the past, many drug release models have been presented which attempt to describe the interaction of drugs and excipients in a formulation. Nevertheless, modeling the intrinsic dissolution behavior is essential for understanding the fundamental dissolution mechanisms of drugs and for enhancing the quality of computational approaches in the long term. Methods: In this study, the intrinsic dissolution of various pharmaceutical model substances (benzocaine, carbamazepine, griseofulvin, ibuprofen, naproxen, phenytoin, theophylline monohydrate, and trimethoprim) was investigated in dissolution experiments, taking into account the flow conditions in a dissolution channel apparatus. A practicable and generally valid representation was identified to describe the diffusion properties of the drugs in terms of the boundary layer thickness without considering the particle size distribution, physical state, or viscoelastic properties. This representation was supported by numerical simulations using a high-resolution mesh. The influence of the topography on the modeling was also examined. Results: Besides the prediction of the influence of a surface reaction limitation or the solubility of a diffusion controlled drug, the boundary layer thickness at the tablet surface is modellable in terms of a freely selectable length and as a function of the diffusion coefficient, drug solubility, and the flow velocity of the dissolution medium. Conclusions: Using different methods and a large dataset, this study presents a modeling approach that can contribute to a deeper understanding of intrinsic dissolution behavior. Full article

Background: Diffuse intrinsic pontine glioma [DIPG] is a fatal pediatric disease characterized by a post-translational modification, a replacement of lysine by methionine in position 27 of the N-terminal [H3K27M] tail of histone 3 isoform-1 [H3.1] or histone 3 isoform-3 [H3.3], respectively, expressed in the DIPG-36 and DIPG-50 cells. We investigated the role of cation channels in DIPG cells for the first time and the effects of ATP-sensitive K⁺[KATP] and TRPV1 channel modulators. Methods: Experiments were performed using “in vitro” cytotoxic assays combined with the patch clamp technique, RT-PCR, Western blot, and flow cytometry assays. Results: The most effective anti-proliferative drugs were repaglinide and glibenclamide after short and long-term incubation [6–96 h]. These drugs reduced macroscopic currents of the DIPG cells recorded in whole-cell patch clamp. Repaglinide concentration dependently enhanced the target protein H3K27ac in Western blotting after 48 h of incubation. This drug reduced cell diameter and enhanced cleaved caspase-3 in DIPG cells; total AKT/mTOR levels and phospho-mTOR were downregulated in DIPG-36. Conclusions: KATP and TRPV1 channels are functionally expressed, and sulphonylureas are effective antiproliferative upregulating H3K27ac with apoptosis in DIPG cells and the sub-micromolar concentrations in DIPG-50. Full article

Background/Objectives: Silybum marianum extract, obtained via microwave-enhanced extraction, was evaluated for its antioxidant, antidiabetic, and antimicrobial activities to explore its therapeutic potential. Methods: The extraction was performed using microwave-enhanced techniques, and LC-MS/MS was employed to profile the metabolites in the extract. Total phenolic and flavonoid contents were quantified using spectrophotometric methods. Antioxidant activity was assessed using DPPH, ABTS, CUPRAC, Phenanthroline, and FRAP assays. Enzyme inhibition assays were conducted to evaluate antidiabetic activity against α-glucosidase and α-amylase. Antimicrobial activity was determined using the disc diffusion method, and in silico ADMET and drug-likeness analyses were performed for key metabolites. Results: The extract contained 251.2 ± 1.2 mg GAE/g of total phenolics and 125.1 ± 1.6 mg QE/g of total flavonoids, with 33 metabolites identified, including phenolic acids, tannins, flavonoids, and flavolignans. Strong antioxidant activity was observed, with IC₅₀ values of 19.2 ± 2.3 μg/mL (DPPH), 7.2 ± 1.7 μg/mL (ABTS), 22.2 ± 1.2 μg/mL (CUPRAC), 35.2 ± 1.8 μg/mL (Phenanthroline), and 24.1 ± 1.2 μg/mL (FRAP). Antidiabetic effects were significant, with IC₅₀ values of 18.1 ± 1.7 μg/mL (α-glucosidase) and 26.5 ± 1.3 μg/mL (α-amylase). Antimicrobial activity demonstrated inhibition zones of 8.9 ± 1.1 mm (Bacillus subtilis), 12.6 ± 1.6 mm (Escherichia coli), 8.2 ± 1.2 mm (Fusarium oxysporum), and 9.2 ± 1.1 mm (Aspergillus niger). In silico analyses showed high absorption, favorable metabolism and excretion, and minimal toxicity, with no hERG channel inhibition or hepatotoxicity. Conclusions: The comprehensive results highlight the significant antioxidant, antidiabetic, and antimicrobial activities of S. marianum extract, suggesting its potential for therapeutic and preventive applications. Full article

Background/Objectives: The etiology of diffuse gingival enlargement is multifactorial, and the definitive diagnosis may be challenging. To highlight the nuances of the differential diagnosis, we present two cases of generalized gingival overgrowth and discuss the diagnostic dilemmas. Case description: In the first case, an 82-year-old male with a medical history of hypertension and prostatitis had a chief complaint of symptomatic oral lesions of a 20-day duration, accompanied by fever and loss of appetite. The clinical examination revealed diffusely enlarged, hemorrhagic, and focally ulcerative upper and lower gingiva, ecchymoses on the buccal mucosa, as well as bilateral cervical lymphadenitis. The histopathologic and immunohistochemical findings combined with the hematologic examination led to a final diagnosis of acute myeloid leukemia, and the patient was referred to a specialized hematology/oncology unit for further management. The second case was a 74-year-old female with a medical history of breast cancer (successfully managed in the past), type II diabetes mellitus, and cardiovascular disease, taking various medications. An intraoral examination revealed diffusely enlarged, erythematous, and hemorrhagic upper and lower gingiva. An incisional biopsy showed hyperplastic granulation and fibrous connective tissue with a predominantly chronic inflammatory infiltrate. Considering the patient’s medical history and current medications, the clinical and microscopic findings were in support of the diagnosis of drug-induced gingival overgrowth associated with calcium channel blocker (amlodipine), partially controlled diabetes serving as an additional predisposing factor. Gingivectomy and periodontal scaling, along with substitution of the offending medication, were curative, and better diabetic control was recommended. Conclusions: Diffuse gingival overgrowth may be caused by a variety of diverse conditions, ranging from an exuberant response to local factors, potentially exacerbated by hormonal influences (e.g., puberty or pregnancy), to drug side effects to genetic, systemic, or even neoplastic diseases. A careful evaluation of the medical and drug history and clinicopathologic correlation is essential for accurate diagnosis and appropriate management. Full article

Background: The effectiveness of paclitaxel (PTX) in treating non-small-cell lung carcinoma (NSCLC) is restricted by its poor pharmacokinetic profile and side effects. This limitation stems from the lack of a suitable delivery vector to efficiently target cancer cells. Therefore, there is a critical need to develop an efficient carrier for the optimised delivery of PTX in NSCLC therapy. Methods: The present study describes the fabrication of mesoporous polydopamine (mPDA) nano-bowls via an emulsion-induced interfacial anisotropic assembly method, designed for efficient entrapment of PTX and pH-responsive release behaviour. Results: The nano-bowls depicted a typical bowl-like shape, with connecting mesoporous channels and a central hollow cavity, allowing optimal loading of PTX. The fabricated nanocarrier system, mPDA-PTX-nb, had a mean hydrodynamic bowl diameter of 200.4 ± 5.2 nm and a surface charge of −39.2 ± 1.3 mV. The entrapment efficiency of PTX within the nano-bowls was found to be 95.7%, with a corresponding release of 85.1% achieved at the acidic pH 5.9 (simulated tumour microenvironment) at 48 h. Drug release was best fitted to the Peppas–Sahlin model, indicating the involvement of both diffusion and relaxation mechanisms. Treatment with mPDA-PTX-nb significantly suppressed A549 lung cancer cell proliferation at 48 and 72 h, resulting in cell viability of 14.0% and 9.3%, respectively, at the highest concentration (100 µg/mL). Conclusions: These results highlight the potential of mPDA-PTX-nb as an effective nanocarrier for PTX, promoting enhanced anti-proliferative effects in NSCLC therapy. Full article

The currently available point-of-care hemostasis tests are burdened by criticisms concerning the use of different activators and inhibitors and the lack of dynamic flow. These operating conditions may constitute an impediment to the determination of the patient’s hemostatic condition. Hence, the diffusion of these tests in clinical practice is still limited to specific scenarios. In this work, we present a new method for analyzing the patient’s global hemostasis based on the visualization of the main components of the coagulation process and its computerized quantitative image analysis. The automated “Smart Clot” point-of-care system presents a micro-fluidic chamber in which whole blood flows, without the addition of any activator or inhibitor. In this micro-channel, platelet adhesion, activation and aggregation to the type I collagen-coated surface take place (primary hemostasis), leading to the production of endogenous thrombin on the surface of platelet aggregates and the consequent fibrin mesh and thrombus formation (secondary hemostasis). These observations are verified by inhibiting primary hemostasis with the antiplatelet drugs Indomethacin (−70% on platelet aggregation, −60% on fibrin(ogen) formation) and Tirofiban (complete inhibition of platelet aggregation and fibrin(ogen) formation) and secondary hemostasis with the antithrombin drugs Heparin (−70% on platelet aggregation, −80% on fibrin(ogen) formation) and Lepirudin (−80% on platelet aggregation, −90% on fibrin(ogen) formation). Smart Clot, through a single test, provides quantitative results concerning platelet aggregation and fibrin formation and is suitable for undergoing comparative studies with other coagulation point-of-care devices. Full article

Organ-on-a-chip technologies show exponential growth driven by the need to reduce the number of experimental animals and develop physiologically relevant human models for testing drugs. In vitro, microfluidic devices should be carefully designed and fabricated to provide reliable tools for modeling physiological or pathological conditions and assessing, for example, drug delivery through biological barriers. The aim of the current study was to optimize the utilization of three existing skin-on-a-chip microfluidic diffusion chambers with various designs. For this, different perfusion flow rates were compared using cellulose acetate membrane, polyester membrane, excised rat skin, and acellular alginate scaffold in the chips. These diffusion platforms were integrated into a single-channel microfluidic diffusion chamber, a multi-channel chamber, and the LiveBox2 system. The experimental results revealed that the 40 µL/min flow rate resulted in the highest diffusion of the hydrophilic model formulation (2% caffeine cream) in each system. The single-channel setup was used for further analysis by computational fluid dynamics simulation. The visualization of shear stress and fluid velocity within the microchannel and the presentation of caffeine progression with the perfusion fluid were consistent with the measured data. These findings contribute to the development and effective application of microfluidic systems for penetration testing. Full article

Light-responsive hydrogels containing light-thermal convertible pigments have received interest for their possible applications in light-responsive shutters, valves, drug delivery systems, etc. However, their utility is limited by the slow response time. In this study, we investigated the use of micro-nano bubble water as a preparation solvent to accelerate the volume phase transition kinetics of poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAM-co-AAc) hydrogels. The hydrogels were characterized by dynamic light scattering (DLS) and dissolved oxygen (DO) measurements. The mechanical properties, surface morphology, and chemical composition of the hydrogels were analyzed by Young’s modulus measurements, scanning electron microscopy (SEM), and Fourier transform infrared (FT-IR) spectroscopy, respectively. The results showed that hydrogels prepared with bubble water changed the volume transition rate by more than two orders of magnitude by simply changing the standing time of the bubble water for only a few hours. The cooperative diffusion coefficients obtained from the light-induced volume transition kinetics correlated linearly with Young’s modulus and metastable state swelling ratio. Our results suggest that bubbles act as efficient water channels, thereby modulating the response rate and providing a simple, additive-free method for preparing hydrogels with a wide range of response rates. Full article

The Internet of bio-nano things (IoBNT) is an emerging paradigm employing nanoscale (~1–100 nm) biological transceivers to collect in vivo signaling information from the human body and communicate it to healthcare providers over the Internet. Bio-nano-things (BNT) offer external actuation of in-body molecular communication (MC) for targeted drug delivery to otherwise inaccessible parts of the human tissue. BNTs are inter-connected using chemical diffusion channels, forming an in vivo bio-nano network, connected to an external ex vivo environment such as the Internet using bio-cyber interfaces. Bio-luminescent bio-cyber interfacing (BBI) has proven to be promising in realizing IoBNT systems due to their non-obtrusive and low-cost implementation. BBI security, however, is a key concern during practical implementation since Internet connectivity exposes the interfaces to external threat vectors, and accurate classification of anomalous BBI traffic patterns is required to offer mitigation. However, parameter complexity and underlying intricate correlations among BBI traffic characteristics limit the use of existing machine-learning (ML) based anomaly detection methods typically requiring hand-crafted feature designing. To this end, the present work investigates the employment of deep learning (DL) algorithms allowing dynamic and scalable feature engineering to discriminate between normal and anomalous BBI traffic. During extensive validation using singular and multi-dimensional models on the generated dataset, our hybrid convolutional and recurrent ensemble (CNN + LSTM) reported an accuracy of approximately ~93.51% over other deep and shallow structures. Furthermore, employing a hybrid DL network allowed automated extraction of normal as well as temporal features in BBI data, eliminating manual selection and crafting of input features for accurate prediction. Finally, we recommend deployment primitives of the extracted optimal classifier in conventional intrusion detection systems as well as evolving non-Von Neumann architectures for real-time anomaly detection. Full article

Nanoparticle-based drugs offer attractive advantages like targeted delivery to the diseased site and size and shape-controlled properties. Therefore, understanding the particulate flow of the nanodrugs is important for effective delivery, accurate prediction of required dosage, and developing efficient drug delivery platforms for nanodrugs. In this study, the transport of nanodrugs including flow velocity and deposition is investigated using three model metal oxide nanodrugs of different sizes including iron oxide, zinc oxide, and combined Cu-Zn-Fe oxide synthesized via a modified polyol approach. The hydrodynamic size, size, morphology, chemical composition, crystal phase, and surface functional groups of the water-soluble nanodrugs were characterized via dynamic light scattering, transmission electron microscopy, scanning electron microscopy-energy dispersive X-ray, X-ray diffraction, and fourier transform infrared spectroscopy, respectively. Two different biomimetic flow channels with customized surfaces are developed via 3D printing to experimentally monitor the velocity and deposition of the different nanodrugs. A diffusion dominated mechanism of flow is seen in size ranges 92 nm to 110 nm of the nanodrugs, from the experimental velocity and mass loss profiles. The flow velocity analysis also shows that the transport of nanodrugs is controlled by sedimentation processes in the larger size ranges of 110–302 nm. However, the combined overview from experimental mass loss and velocity trends indicates presence of both diffusive and sedimentation forces in the 110–302 nm size ranges. It is also discovered that the nanodrugs with higher positive surface charges are transported faster through the two test channels, which also leads to lower deposition of these nanodrugs on the walls of the flow channels. The results from this study will be valuable in realizing reliable and cost-effective in vitro experimental approaches that can support in vivo methods to predict the flow of new nanodrugs. Full article

Tumor-on-chips have become an effective resource in cancer research. However, their widespread use remains limited due to issues related to their practicality in fabrication and use. To address some of these limitations, we introduce a 3D-printed chip, which is large enough to host ~1 cm³ of tissue and fosters well-mixed conditions in the liquid niche, while still enabling the formation of the concentration profiles that occur in real tissues due to diffusive transport. We compared the mass transport performance in its rhomboidal culture chamber when empty, when filled with GelMA/alginate hydrogel microbeads, or when occupied with a monolithic piece of hydrogel with a central channel, allowing communication between the inlet and outlet. We show that our chip filled with hydrogel microspheres in the culture chamber promotes adequate mixing and enhanced distribution of culture media. In proof-of-concept pharmacological assays, we biofabricated hydrogel microspheres containing embedded Caco2 cells, which developed into microtumors. Microtumors cultured in the device developed throughout the 10-day culture showing >75% of viability. Microtumors subjected to 5-fluorouracil treatment displayed <20% cell survival and lower VEGF-A and E-cadherin expression than untreated controls. Overall, our tumor-on-chip device proved suitable for studying cancer biology and performing drug response assays. Full article

In medical validation experiments, such as drug testing and clinical trials, 3D bioprinted biomimetic tissues, especially those containing blood vessels, can be used to replace animal models. The difficulty in the viability of printed biomimetic tissues, in general, lies in the provision of adequate oxygen and nutrients to the internal regions. This is to ensure normal cellular metabolic activity. The construction of a flow channel network in the tissue is an effective way to address this challenge by both allowing nutrients to diffuse and providing sufficient nutrients for internal cell growth and by removing metabolic waste in a timely manner. In this paper, a three-dimensional TPMS vascular flow channel network model was developed and simulated to analyse the effect of perfusion pressure on blood flow rate and vascular-like flow channel wall pressure when the perfusion pressure varies. Based on the simulation results, the in vitro perfusion culture parameters were optimised to improve the structure of the porous structure model of the vascular-like flow channel, avoiding perfusion failure due to unreasonable perfusion pressure settings or necrosis of cells without sufficient nutrients due to the lack of fluid passing through some of the channels, and the research work promotes the development of tissue engineering in vitro culture. Full article

Polyhydroquinoline (PHQ) are the unsymmetrical Hantzsch derivatives of 1,4-dihydropyridines with several biological applications. In this work, twenty-five (3–27) new Schiff’s base derivatives of polyhydroquinoline hydrazide were synthesized in excellent to good yields by a multi-component reaction. The structures of the synthesized products (1–27) were deduced with the help of spectroscopic techniques, such as ¹H-, ¹³C -NMR, and HR-ESI-MS. The synthesized products (1–27) were tested for their antibacterial and in vitro calcium -channel-blocking (CCB) potentials using the agar-well diffusion method, and isolated rat aortic ring preparations, respectively. Among the series, sixteen compounds were found to inhibit the growth of Escherichia coli and Enterococcus faecalis. Among them, compound 17 was observed to be the most potent one at a dose 2 µg/mL, with an 18 mm zone of inhibition against both bacteria when it was compared with the standard drug amoxicillin. Eight compounds showed CCB activity of variable potency; in particular, compound 27 was more potent, with an EC₅₀ value of 0.7 (0.3–1.1) µg/mL, indicating their CCB effect. Full article

Generating and maintaining the concentration dilutions of diffusible molecules in microchannels is critical for high-throughput chemical and biological analysis. Conventional serial network microfluidic technologies can generate high orders of arbitrary concentrations by a predefined microchannel network. However, a previous design requires a large occupancy area and is unable to dynamically generate different profiles in the same chip, limiting its applications. This study developed a microfluidic device enabling dynamic variations of both the concentration in the same channel and the concentration distribution in multiple channels by adjusting the flow resistance using programmable pneumatic microvalves. The key component (the pneumatic microvalve) allowed dynamic adjustment of the concentration profile but occupied a tiny space. Additionally, a Matlab program was developed to calculate the flow rates and flow resistance of various sections of the device, which provided theoretical guidance for dimension design. In silico investigations were conducted to evaluate the microvalve deformation with widths from 100 to 300 µm and membrane thicknesses of 20 and 30 µm under the activation pressures between 0 and 2000 mbar. The flow resistance of the deformed valve was studied both numerically and experimentally and an empirical model for valve flow resistance with the form of $R_h=a{e}^{bP}$ was proposed. Afterward, the fluid flow in the valve region was characterized using Micro PIV to further demonstrate the adjustment mechanism of the flow resistance. Then, the herringbone structures were employed for fast mixing to allow both quick variation of concentration and minor space usage of the channel network. Finally, an empirical formula-supported computational program was developed to provide the activation pressures required for the specific concentration profile. Both linear ($C_k$ = −0.2k + 1) and nonlinear $(C_k$ = ${\left(\frac{1}{\sqrt{10}}\right)}^k)$ concentration distribution in four channels were varied using the same device by adjusting microvalves. The device demonstrated the capability to control the concentration profile dynamically in a small space, offering superior application potentials in analytical chemistry, drug screening, and cell biology research. Full article

Superdiffusion processes significantly promote the transport of tiny passive particles within biological fluids. Activity, one of the essential measures for living matter, however, is less examined in terms of how and to what extent it can improve the diffusivity of the moving particles. Here, bacterial suspensions are confined within the microfluidic channel at the state of bacterial turbulence, and are tuned to different activity levels by oxygen consumption in control. Systematic measurements are conducted to determine the superdiffusion exponent, which characterizes the diffusivity strength of tracer particles, depending on the continuously injecting energy converted to motile activity from swimming individuals. Higher activity is quantified to drastically enhance the superdiffusion process of passive tracers in the short-time regime. Moreover, the number density of the swimming bacteria is controlled to contribute to the field activity, and then to strengthen the super-diffusivity of tracers, distinguished by regimes with and without collective motion of interacting bacteria. Finally, the non-slip surfaces of the microfluidic channel lower the superdiffusion of immersed tracers due to the resistance, with the small diffusivity differing from the counterpart in the bulk. The findings here suggest ways of controlled diffusion and transport of substances within the living system with different levels of nutrition and resources and boundary walls, leading to efficient mixing, drug delivery and intracellular communications. Full article