-
Biomaterials Advances Sep 2024Microbial colonization and development of infections in wounds is a sign of chronicity. The prevailing approach to manage and treat these wounds involves dressings....
Microbial colonization and development of infections in wounds is a sign of chronicity. The prevailing approach to manage and treat these wounds involves dressings. However, these often fail in effectively addressing infections, as they struggle to both absorb exudates and maintain optimal local moisture. The system here presented was conceptualized with a three-layer design: the outer layer made of a fibrous polycaprolactone (PCL) film, to act as a barrier for preventing microorganisms and impurities from reaching the wound; the intermediate layer formed of a sodium alginate (SA) hydrogel loaded with ampicillin (Amp) for fighting infections; and the inner layer comprised of a fibrous film of PCL and polyethylene glycol (PEG) for facilitating cell recognition and preventing wound adhesion. Thermal evaluations, degradation, wettability and release behavior testing confirmed the system resistance overtime. The sandwich demonstrated the capability for absorbing exudates (≈70 %) and exhibited a controlled release of Amp for up to 24 h. Antimicrobial testing was performed against Staphylococcus aureus and Escherichia coli, as representatives of Gram-positive and Gram-negative bacteria: >99 % elimination of bacteria. Cell cytotoxicity assessments showed high cytocompatibility levels, confirming the safety of the proposed sandwich system. Adhesion assays confirmed the system ease of detaching without mechanical effort (0.37 N). Data established the efficiency of the sandwich-like system, suggesting promising applications in infected wound care.
Topics: Alginates; Wound Infection; Staphylococcus aureus; Escherichia coli; Anti-Bacterial Agents; Polyesters; Ampicillin; Humans; Hydrogels; Polyethylene Glycols; Animals; Bandages; Microbial Sensitivity Tests; Mice; Wound Healing
PubMed: 38924805
DOI: 10.1016/j.bioadv.2024.213931 -
CPT: Pharmacometrics & Systems... Jun 2024Significant pharmacokinetic (PK) differences exist between different forms of valproic acid (VPA), such as syrup and sustained-release (SR) tablets. This study aimed to...
Significant pharmacokinetic (PK) differences exist between different forms of valproic acid (VPA), such as syrup and sustained-release (SR) tablets. This study aimed to develop a population pharmacokinetic (PopPK) model for VPA in children with epilepsy and offer dose adjustment recommendation for switching dosage forms as needed. The study collected 1411 VPA steady-state trough concentrations (C) from 617 children with epilepsy. Using NONMEM software, a PopPK model was developed, employing a stepwise approach to identify possible variables such as demographic information and concomitant medications. The final model underwent internal and external evaluation via graphical and statistical methods. Moreover, Monte Carlo simulations were used to generate a dose tailoring strategy for typical patients weighting 20-50 kg. As a result, the PK characteristics of VPA were described using a one-compartment model with first-order absorption. The absorption rate constant (k) was set at 2.64 and 0.46 h for syrup and SR tablets. Body weight and sex were identified as significant factors affecting VPA's pharmacokinetics. The final PopPK model demonstrated acceptable prediction performance and stability during internal and external evaluation. For children taking syrup, a daily dose of 25 mg/kg resulted in the highest probability of achieving the desired target C, while a dose of 20 mg/kg/day was appropriate for those taking SR tablets. In conclusion, we established a PopPK model for VPA in children with epilepsy to tailor VPA dosage when switching between syrup and SR tablets, aiming to improve plasma VPA concentrations fluctuations.
PubMed: 38923247
DOI: 10.1002/psp4.13191 -
Clinical Oral Investigations Jun 2024The primary objective of this in vitro experiment was an assessment of proliferative capacity, metabolic activity, and potential cellular detriment of human periodontal...
OBJECTIVES
The primary objective of this in vitro experiment was an assessment of proliferative capacity, metabolic activity, and potential cellular detriment of human periodontal ligament cells (hPDL) exposed to cigarette smoke (CS), electronic cigarette vapor (eCV), and heated tobacco product aerosol (HTP), or air (control).
MATERIALS AND METHODS
Using a CAD/CAM-designed exposition chamber, hPDL were exposed to CS, eCV, HTP, or air (control) based on the Health Canada Intense Smoking Regime. Cell proliferation, metabolic activity, and cellular detriment were assessed at various time points.
RESULTS
Compared to the control, hPDL exposed to CS exhibited significantly decreased cell numbers at all time points. HTP exposure led to reduced cell numbers 48 h and 72 h post-exposure, while eCV-exposed cells showed no significant decrease. The metabolic activity of eCV-treated hPDL was slightly reduced at 7 h but recovered at 24 h and 48 h. In contrast, CS-treated cells exhibited significantly decreased metabolic activity at 24 h and 48 h, and HTP-exposed cells showed a significant decrease after 48 h. Flow cytometry indicated both apoptotic and necrotic cell death following CS exposure, with necrotic cell death being more pronounced.
CONCLUSIONS
eCV and HTP demonstrated comparatively reduced detrimental effects on hPDL compared to CS.
CLINICAL RELEVANCE
The findings suggest that conventional cigarette smoke poses a substantial risk to periodontal health by significantly impairing cell proliferation and metabolic activity. However, alternatives such as eCV and HTP may offer a comparatively reduced risk.
Topics: Periodontal Ligament; Humans; Cell Proliferation; Cells, Cultured; Electronic Nicotine Delivery Systems; Tobacco Products; Flow Cytometry; In Vitro Techniques; Smoke; E-Cigarette Vapor; Aerosols; Nicotine; Apoptosis
PubMed: 38922383
DOI: 10.1007/s00784-024-05797-x -
Anais Da Academia Brasileira de Ciencias 2024The ecology of movement is an expanding area, marked by the diversity of analytical methods and protocols, which enables this integrative reading. We investigated...
Tracking the little ones: use of fluorescent powder to follow a leaf litter lizard (Coleodactylus meridionalis, Squamata: Sphaerodactylidae) in the Atlantic Forest of southern Bahia, Brazil.
The ecology of movement is an expanding area, marked by the diversity of analytical methods and protocols, which enables this integrative reading. We investigated movement ecology aspects of Coleodactylus meridionalis in southern Bahia, northeastern Brazil, using fluorescent powder with mineral oil to track individuals. We monitored 69 individuals of C. meridionalis that walked an average distance of 148 cm in 2h. We identified this movement as foraging due to the orientation of the step sequence and microenvironments used. We find no significant differences between walking distance and weight. However, we found a decrease in activity over the follow-up period. Most of the lizard's movements were directed north, while south, east, and west were followed equally. The individuals stayed predominantly on the ground (leaf litter), but it was possible to observe the use of other surfaces, such as trunks and burrows on the ground. Therefore, we studied the movement in three dimensions (ground height, distance traveled, and orientation of steps). We observed the lizard's foraging, one of the most common and least investigated movements in small lizards like C. meridionalis. This involves not only the species' activity schedule but other intrinsic and extrinsic factors that shape the movement decisions of individuals.
Topics: Animals; Lizards; Brazil; Forests; Powders; Male
PubMed: 38922256
DOI: 10.1590/0001-3765202420230728 -
Cells Jun 2024Exposure to cigarette smoke is known to induce disease during pregnancy. Recent evidence showed that exposure to secondhand smoke (SHS) negatively impacts fetal and...
Exposure to cigarette smoke is known to induce disease during pregnancy. Recent evidence showed that exposure to secondhand smoke (SHS) negatively impacts fetal and placental weights, leading to the development of intrauterine growth restriction (IUGR). Electronic cigarettes (eCigs) represent a phenomenon that has recently emerged, and their use is also steadily rising. Even so, the effects of SHS or eCigs during gestation remain limited. In the present study, we wanted to characterize the effects of SHS or eCig exposure at two different important gestational points during mouse pregnancy. C57/Bl6 mice were exposed to SHS or eCigs via a nose-only delivery system for 4 days (from 14.5 to 17.5 gestational days (dGA) or for 6 days (from 12.5 dGA to 17.5 dGA)). At the time of necropsy (18.5 dGA), placental and fetal weights were recorded, maternal blood pressure was determined, and a dipstick test to measure proteinuria was performed. Placental tissues were collected, and inflammatory molecules in the placenta were identified. Treatment with SHS showed the following: (1) a significant decrease in placental and fetal weights following four days of exposure, (2) higher systolic and diastolic blood pressure following six days of exposure, and (3) increased proteinuria after six days of exposure. Treatment with eCigs showed the following: (1) a significant decrease in placental weight and fetal weight following four or six days of exposure, (2) higher systolic and diastolic blood pressure following six days of exposure, and (3) increased proteinuria after six days of exposure. We also observed different inflammatory markers associated with the development of IUGR or PE. We conclude that the detrimental effects of SHS or eCig treatment coincide with the length of maternal exposure. These results could be beneficial in understanding the long-term effects of SHS or eCig exposure in the development of placental diseases.
Topics: Pregnancy; Female; Animals; Tobacco Smoke Pollution; Mice; Mice, Inbred C57BL; Placenta; Placenta Diseases; E-Cigarette Vapor; Maternal Exposure; Blood Pressure; Fetal Growth Retardation; Electronic Nicotine Delivery Systems
PubMed: 38920640
DOI: 10.3390/cells13121009 -
Journal of Biosciences 2024Fibroblasts embedded in a 3D matrix microenvironment can remodel the matrix to regulate cell adhesion and function. Collagen hydrogels are a useful system to study...
Fibroblasts embedded in a 3D matrix microenvironment can remodel the matrix to regulate cell adhesion and function. Collagen hydrogels are a useful system to study cell-matrix interactions in a 3D microenvironment. While major matrix reorganizations are easily recognizable, subtle changes in response to environmental or biochemical cues are challenging to discern in 3D hydrogels. Three-dimensional collagen gels at 1.0 mg/ml vs 1.5 mg/ml were labelled with DQ-collagen and imaged by confocal reflectance microscopy to evaluate these small changes. An image analysis pipeline was developed, hydrogel area and number of crosssections analysed were optimized, and fibrillar collagen properties (number of branches, number of junctions, and average branch length) were quantified. While no significant changes were seen in fibrillar collagen organization between 1.0 mg/ml and 1.5 mg/ml collagen hydrogels, embedded mouse fibroblasts caused a significant increase in collagen branching and organization. Using the phalloidin-labelled cells, this change was quantitated in immediate proximity of the cell. A distinct increase in branch and junction numbers was observed, significantly altered by small changes in collagen concentration (1.0 mg/ml vs 1.5 mg/ml). Together, this analysis gives a quantitative evaluation of how cells respond to and modify their immediate microenvironment in a 3D collagen hydrogel.
Topics: Hydrogels; Animals; Fibroblasts; Mice; Extracellular Matrix; Fibrillar Collagens; Microscopy, Confocal; Collagen; Cell Adhesion
PubMed: 38920105
DOI: No ID Found -
Journal of the Royal Society, Interface Jun 2024The inactivation of viruses in aerosol particles (aerosols) and droplets depends on many factors, but the precise mechanisms of inactivation are not known. The system... (Review)
Review
The inactivation of viruses in aerosol particles (aerosols) and droplets depends on many factors, but the precise mechanisms of inactivation are not known. The system involves complex physical and biochemical interactions. We reviewed the literature to establish current knowledge about these mechanisms and identify knowledge gaps. We identified 168 relevant papers and grouped results by the following factors: virus type and structure, aerosol or droplet size, temperature, relative humidity (RH) and evaporation, chemical composition of the aerosol or droplet, pH and atmospheric composition. These factors influence the dynamic microenvironment surrounding a virion and thus may affect its inactivation. Results indicate that viruses experience biphasic decay as the carrier aerosols or droplets undergo evaporation and equilibrate with the surrounding air, and their final physical state (liquid, semi-solid or solid) depends on RH. Virus stability, RH and temperature are interrelated, but the effects of RH are multifaceted and still not completely understood. Studies on the impact of pH and atmospheric composition on virus stability have raised new questions that require further exploration. The frequent practice of studying virus inactivation in large droplets and culture media may limit our understanding of inactivation mechanisms that are relevant for transmission, so we encourage the use of particles of physiologically relevant size and composition in future research.
Topics: Aerosols; Virus Inactivation; Humans; Hydrogen-Ion Concentration; Humidity; Temperature; Particle Size; Virion
PubMed: 38920060
DOI: 10.1098/rsif.2024.0018 -
Patient Preference and Adherence 2024There is no consistent framework for patient-centric drug product design, despite the common understanding that drug product acceptability and preferences influence... (Review)
Review
BACKGROUND
There is no consistent framework for patient-centric drug product design, despite the common understanding that drug product acceptability and preferences influence adherence and, therefore, drug product effectiveness. The aim of this review was to assess current understanding of patient acceptability and preferences for solid oral dosage form (SODF) drug product attributes, and the potential impact of these attributes on patient behaviors and outcomes.
PATIENTS AND METHODS
A scoping review was conducted. Embase, Ovid MEDLINE, and PubMed were searched for full-text articles published between January 2013 and May 2023. Following screening and assessment against predefined inclusion criteria, data were analyzed thematically.
RESULTS
Nineteen studies were included. Four overarching domains of drug product attributes were identified and summarized in a framework: appearance, swallowability, palatability, and handling. Each domain was informed by specific drug product attributes: texture, form, size, shape, color, marking, taste, mouthfeel, and smell. The most frequently studied domains were swallowability and appearance, while the most studied attributes were size, shape, and texture. Smell, marking, and mouthfeel were the least studied attributes. Texture intersected all domains, while form, shape, and size intersected appearance, swallowability, and handling. Swallowability and size appeared to be the key domain and attribute, respectively, to consider when designing drug products. Few studies explored the impact of drug product attributes on behaviors and outcomes.
CONCLUSION
While existing studies of drug product attributes have focused on appearance and swallowability, this review highlighted the importance of two less well-understood domains-palatability and handling-in understanding patients' acceptability and preferences for SODF drug products. The framework provides a tool to facilitate patient-centric design of drug products, organizing and categorizing physical drug product attributes into four overarching domains (appearance, swallowability, palatability, and handling), encouraging researchers to comprehensively assess the impact of drug product attributes on patient acceptability, preferences, and outcomes.
PubMed: 38919378
DOI: 10.2147/PPA.S443213 -
Journal of Nanobiotechnology Jun 2024Bacteriophages (phages) represent a unique category of viruses with a remarkable ability to selectively infect host bacteria, characterized by their assembly from... (Review)
Review
Bacteriophages (phages) represent a unique category of viruses with a remarkable ability to selectively infect host bacteria, characterized by their assembly from proteins and nucleic acids. Leveraging their exceptional biological properties and modifiable characteristics, phages emerge as innovative, safe, and efficient delivery vectors. The potential drawbacks associated with conventional nanocarriers in the realms of drug and gene delivery include a lack of cell-specific targeting, cytotoxicity, and diminished in vivo transfection efficiency. In contrast, engineered phages, when employed as cargo delivery vectors, hold the promise to surmount these limitations and attain enhanced delivery efficacy. This review comprehensively outlines current strategies for the engineering of phages, delineates the principal types of phages utilized as nanocarriers in drug and gene delivery, and explores the application of phage-based delivery systems in disease therapy. Additionally, an incisive analysis is provided, critically examining the challenges confronted by phage-based delivery systems within the domain of nanotechnology. The primary objective of this article is to furnish a theoretical reference that contributes to the reasoned design and development of potent phage-based delivery systems.
Topics: Bacteriophages; Humans; Nanomedicine; Drug Delivery Systems; Animals; Gene Transfer Techniques; Drug Carriers; Nanoparticles; Nanotechnology
PubMed: 38918839
DOI: 10.1186/s12951-024-02576-4 -
Journal of Nanobiotechnology Jun 2024Hemangioma of infancy is the most common vascular tumor during infancy and childhood. Despite the proven efficacy of propranolol treatment, certain patients still...
Hemangioma of infancy is the most common vascular tumor during infancy and childhood. Despite the proven efficacy of propranolol treatment, certain patients still encounter resistance or face recurrence. The need for frequent daily medication also poses challenges to patient adherence. Bleomycin (BLM) has demonstrated effectiveness against vascular anomalies, yet its use is limited by dose-related complications. Addressing this, this study proposes a novel approach for treating hemangiomas using BLM-loaded hyaluronic acid (HA)-based microneedle (MN) patches. BLM is encapsulated during the synthesis of polylactic acid (PLA) microspheres (MPs). The successful preparation of PLA MPs and MN patches is confirmed through scanning electron microscopy (SEM) images. The HA microneedles dissolve rapidly upon skin insertion, releasing BLM@PLA MPs. These MPs gradually degrade within 28 days, providing a sustained release of BLM. Comprehensive safety assessments, including cell viability, hemolysis ratio, and intradermal reactions in rabbits, validate the safety of MN patches. The BLM@PLA-MNs exhibit an effective inhibitory efficiency against hemangioma formation in a murine hemangioma model. Of significant importance, RNA-seq analysis reveals that BLM@PLA-MNs exert their inhibitory effect on hemangiomas by regulating the P53 pathway. In summary, BLM@PLA-MNs emerge as a promising clinical candidate for the effective treatment of hemangiomas.
Topics: Bleomycin; Animals; Mice; Rabbits; Hemangioma; Hyaluronic Acid; Needles; Delayed-Action Preparations; Drug Delivery Systems; Polyesters; Humans; Microspheres; Antibiotics, Antineoplastic; Drug Liberation
PubMed: 38918811
DOI: 10.1186/s12951-024-02557-7