-
Proceedings of the National Academy of... Sep 2021Bacterial suspensions show turbulence-like spatiotemporal dynamics and vortices moving irregularly inside the suspensions. Understanding these ordered vortices is an...
Bacterial suspensions show turbulence-like spatiotemporal dynamics and vortices moving irregularly inside the suspensions. Understanding these ordered vortices is an ongoing challenge in active matter physics, and their application to the control of autonomous material transport will provide significant development in microfluidics. Despite the extensive studies, one of the key aspects of bacterial propulsion has remained elusive: The motion of bacteria is chiral, i.e., it breaks mirror symmetry. Therefore, the mechanism of control of macroscopic active turbulence by microscopic chirality is still poorly understood. Here, we report the selective stabilization of chiral rotational direction of bacterial vortices in achiral circular microwells sealed by an oil/water interface. The intrinsic chirality of bacterial swimming near the top and bottom interfaces generates chiral collective motions of bacteria at the lateral boundary of the microwell that are opposite in directions. These edge currents grow stronger as bacterial density increases, and, within different top and bottom interfaces, their competition leads to a global rotation of the bacterial suspension in a favored direction, breaking the mirror symmetry of the system. We further demonstrate that chiral edge current favors corotational configurations of interacting vortices, enhancing their ordering. The intrinsic chirality of bacteria is a key feature of the pairing order transition from active turbulence, and the geometric rule of pairing order transition may shed light on the strategy for designing chiral active matter.
Topics: Bacteria; Bacteriological Techniques; Escherichia coli; Models, Biological; Suspensions
PubMed: 34561308
DOI: 10.1073/pnas.2107461118 -
Journal of Feline Medicine and Surgery Jun 2021The aim of this study was to determine famciclovir content (strength) in compounded formulations and to determine if potency changed over time.
OBJECTIVES
The aim of this study was to determine famciclovir content (strength) in compounded formulations and to determine if potency changed over time.
METHODS
Four concentrations of oral oil suspension in three distinct flavors, three concentrations of oral paste, three chew treats and 62.5 mg tablets from one compounding pharmacy were evaluated for famciclovir content. Specific sample preparation procedures were used for each drug formulation prior to determination of famciclovir content through mass spectrometry tandem liquid chromatography. Analysis was performed on arrival from the compounder and on days 7, 14, 28, 56 and 120. Samples were run in triplicate and concentration determined by comparison with a standard curve. Content was considered appropriate if within 90-110% of the labeled concentration.
RESULTS
On arrival from the compounding pharmacy, 5/12 oral oil suspensions of varying concentrations were <90% of the labeled concentration and 3/3 oral pastes were >110%. Famciclovir content in oil suspensions ranged from 72% to 118% of the label value while oral pastes ranged from 95% to 202% of the label concentration over the 120 study days, and all concentrations varied in an unpredictable fashion. Tablets contained 90-110% of the labeled value throughout the study period. Chew treats could not be successfully analyzed.
CONCLUSIONS AND RELEVANCE
This study found substantial variation in famciclovir content in the compounded products evaluated, which, in turn, raises concerns that substandard dosing could result in lack of efficacy or a failed treatment trial. Drug toxicity might also be encountered. Veterinarians must be aware that while compounded medications can improve compliance, they might not deliver the drug dose expected.
Topics: Administration, Oral; Animals; Drug Compounding; Drug Stability; Famciclovir; Suspensions
PubMed: 33019848
DOI: 10.1177/1098612X20961046 -
Journal of Controlled Release :... Sep 2022Drug delivery to the suprachoroidal space (SCS®) has become a clinical reality after the 2021 FDA approval of CLS-TA, a triamcinolone acetonide injectable suspension...
Drug delivery to the suprachoroidal space (SCS®) has become a clinical reality after the 2021 FDA approval of CLS-TA, a triamcinolone acetonide injectable suspension for suprachoroidal use (XIPERE®), administered via a microneedle-based device, the SCS Microinjector®. Suprachoroidal (SC) delivery facilitates targeting, compartmentalization, and durability of small molecule suspensions, thereby potentially addressing some of the efficacy, safety, and treatment burden limitations of current retinal therapies. Herein, the design features of the SCS Microinjector are reviewed, along with the biomechanics of SC drug delivery. Also presented are preclinical evaluations of SC small molecule suspensions from 4 different therapeutic classes (plasma kallikrein inhibitor, receptor tyrosine kinase inhibitor, corticosteroid, complement factor D inhibitor), highlighting their potential for durability, targeted compartmentalization, and acceptable safety profiles following microinjector-based SC delivery. The clinical evaluations of the safety, tolerability and efficacy of SC delivered triamcinolone further supports potential of SC small molecule suspensions as a clinically viable strategy for the treatment of chorioretinal diseases. Also highlighted are current limitations, key pharmacological considerations, and future opportunities to optimize the SC microinjector platform for safe, effective, and potentially long-acting drug delivery for the treatment of chorioretinal disorders.
Topics: Choroid; Complement Factor D; Plasma Kallikrein; Protein Kinase Inhibitors; Suspensions; Triamcinolone Acetonide
PubMed: 35868358
DOI: 10.1016/j.jconrel.2022.05.061 -
Scientific Reports Jan 2018Posaconazole is a triazole antifungal used to prevent invasive fungal infections (IFIs) in patients receiving chemotherapy or haemotopoietic stem cell transplantation.... (Observational Study)
Observational Study
Prevention of Invasive Aspergillus Fungal Infections with the Suspension and Delayed-Release Tablet Formulations of Posaconazole in Patients with Haematologic Malignancies.
Posaconazole is a triazole antifungal used to prevent invasive fungal infections (IFIs) in patients receiving chemotherapy or haemotopoietic stem cell transplantation. Due to highly variable bioavailability of the oral suspension formulation, a delayed-release tablet was developed which showed improved bioavailability. A minimal target posaconazole plasma concentration of 0.7 mg/L is recommended for prophylaxis of IFIs. However, the relationship between plasma concentration of posaconazole and its efficacy against IFIs remains unclear. We analysed trough posaconazole concentrations and response against IFIs in 50 and 104 patients with haematologic malignancies receiving prophylactic posaconazole as the tablet or suspension formulation, respectively. Mean plasma concentration of posaconazole was 1.91 ± 1.06 mg/L and 0.82 ± 0.57 mg/L in the tablet and the oral suspension group, respectively (p < 0.0001). The percentage of patients reaching the minimal target concentration of 0.7 mg/L was 92.0% and 47.1% in the tablet and oral suspension groups, respectively (p < 0.0001). Emergent aspergillosis occurred in 9 (8.7%) patients in the suspension group and in none of the patients taking the tablet formulation (p = 0.032). Our results show a relationship between plasma concentrations of posaconazole and its prophylactic efficacy in patients with haematologic malignancies. Target posaconazole concentrations are reached more efficiently with the tablet than with the suspension formulation.
Topics: Adult; Aged; Antifungal Agents; Chemoprevention; Delayed-Action Preparations; Female; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Male; Middle Aged; Plasma; Suspensions; Tablets; Treatment Outcome; Triazoles
PubMed: 29374234
DOI: 10.1038/s41598-018-20136-3 -
Soft Matter Mar 2022Few techniques can reliably measure the dynamics of colloidal suspensions or other soft materials over a wide range of turbidities. Here we systematically investigate...
Few techniques can reliably measure the dynamics of colloidal suspensions or other soft materials over a wide range of turbidities. Here we systematically investigate the capability of Differential Dynamic Microscopy (DDM) to characterise particle dynamics in turbid colloidal suspensions based on brightfield optical microscopy. We measure the Intermediate Scattering Function (ISF) of polystyrene microspheres suspended in water over a range of concentrations, turbidities, and up to 4 orders of magnitude in time-scales. These DDM results are compared to data obtained from both Dynamic Light Scattering (DLS) and Two-colour Dynamic Light Scattering (TCDLS). The latter allows for suppression of multiple scattering for moderately turbid suspensions. We find that DDM can obtain reliable diffusion coefficients at up to 10 and 1000 times higher particle concentrations than TCDLS and standard DLS, respectively. Additionally, we investigate the roles of the four length-scales relevant when imaging a suspension: the sample thickness , the imaging depth , the imaging depth of field DoF, and the photon mean free path . More detailed experiments and analysis reveal the appearance of a short-time process as turbidity is increased, which we associate with multiple scattering events within the imaging depth of the field. The long-time process corresponds to the particle dynamics from which particle-size can be estimated in the case of non-interacting particles. Finally, we provide a simple theoretical framework, ms-DDM, for turbid samples, which accounts for multiple scattering.
Topics: Dynamic Light Scattering; Microscopy; Particle Size; Photons; Suspensions
PubMed: 35171181
DOI: 10.1039/d1sm01598b -
Burns : Journal of the International... Sep 2021This systematic review evaluated the efficacy of autologous skin cell suspensions (ASCS) on the re-epithelialization of partial thickness burn injuries and skin graft... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of randomized trials evaluating the efficacy of autologous skin cell suspensions for re-epithelialization of acute partial thickness burn injuries and split-thickness skin graft donor sites.
BACKGROUND
This systematic review evaluated the efficacy of autologous skin cell suspensions (ASCS) on the re-epithelialization of partial thickness burn injuries and skin graft donor site wounds.
METHODS
Four databases (EMBASE, Google Scholar, MEDLINE, Web of Science), grey literature and select journal hand-searching identified studies from 1975 - 2020. Randomized trials evaluating partial thickness burn management with non-cultured ASCS compared to any other intervention were included. Time to re-epithelialization (TTRE) was the primary outcome. Three independent researchers completed screening, data extraction and certainty of evidence assessment using Cochrane Risk of Bias Tool and Grading of Recommendations Assessment, Development and Evaluation.
RESULTS
Five trials (n = 347) reported on adults (2 trials) and children (1 trial) with burn wounds, and adults with donor site wounds (2 trials). The effect of ASCS compared to control on TTRE in adult burn wounds was not estimable. TTRE was shorter in pediatric burn wounds (SMD -1.75 [95% CI: -3.45 to -0.05]) and adult donor site wounds (SMD-5.71 [95% CI: -10.61 to-0.81]) treated with ASCS. The certainty of evidence was very low.
CONCLUSION
Compared to standard care, ACSC may reduce pediatric partial thickness burn wound and adult split-thickness skin graft donor site TTRE.
REGISTRATION
PROSPERO CRD42019133171.
Topics: Burns; Child; Humans; Randomized Controlled Trials as Topic; Re-Epithelialization; Skin Transplantation; Soft Tissue Injuries; Suspensions; Wound Healing
PubMed: 33941398
DOI: 10.1016/j.burns.2021.04.005 -
Drug Design, Development and Therapy 2022The purpose of this work was to develop an ivacaftor self-nanoemulsion drug delivery system (IVA-SNEDDS) using the newly developed double headed miscellaneous lipid...
PURPOSE
The purpose of this work was to develop an ivacaftor self-nanoemulsion drug delivery system (IVA-SNEDDS) using the newly developed double headed miscellaneous lipid (DHML) as oil phase to reduce the food effect and inter-individual absorption variability of IVA.
METHODS
The lipids with the greatest solubility to IVA were selected as the oil phase of IVA-SNEDDS by saturation solubility method. Then, among different surfactants and co-surfactants, those with good emulsifying ability for the selected oil phase were selected, and the proportion of surfactant and co-surfactant was further selected by pseudo-ternary phase diagram. The prepared IVA-SNEDDS were screened and evaluated in vitro and in beagle dogs.
RESULTS
The optimized IVA-SNEDDS formulation consisting of DHML, Tween 80, and Transcutol HP with the weight ratio of 2:2:1 was physically stable and it was easy to disperse in water, pH 1.2 hydrochloric acid and pH 6.8 phosphate buffer solution, and generated a fine homogeneous nanoemulsion, with mean globule size less than 75 nm regardless of dilution ratio. In vitro drug release studies showed that the drug in IVA-SNEDDS could be completely released in a short time, while the drug release in IVA-suspension was less than 1% at 60 min. In vivo, using IVA-suspension (Fed) as a reference, the relative oral bioavailability of IVA-suspension (Fasted), IVA-SNEDDS (Fasted), and IVA-SNEDDS (Fed) were 23.35%, 153.63%, and 149.89%, respectively. This showed that IVA-SNEDDS could eliminate the positive food effect, improve the oral bioavailability, and reduce the IVA absorption difference between individuals.
CONCLUSION
As the oil phase of SNEDDS, DHML can significantly improve the drug solubility and drug loading of IVA-SNEDDS. Moreover, DHML was easily emulsified and can effectively form a nanoemulsion in vivo and in vitro. The prepared IVA-SNEDDS can reduce the inter-individual absorption variability of IVA, eliminate its food effect and improve its oral bioavailability.
Topics: Aminophenols; Animals; Biological Availability; Dogs; Drug Delivery Systems; Emulsions; Nanoparticles; Particle Size; Quinolones; Surface-Active Agents; Suspensions
PubMed: 35637746
DOI: 10.2147/DDDT.S356967 -
Journal of the Royal Society, Interface Feb 2023Sinking or sedimentation of biological aggregates plays a critical role in carbon sequestration in the ocean and in vertical material fluxes in wastewater treatment...
Sinking or sedimentation of biological aggregates plays a critical role in carbon sequestration in the ocean and in vertical material fluxes in wastewater treatment plants. In both these contexts, the sinking aggregates are 'active', since they are biological hot-spots and are densely colonized by microorganisms including bacteria and sessile protists, some of which generate feeding currents. However, the effect of these feeding currents on the sinking rates, trajectories and mass transfer to these 'active sinking particles' has not previously been studied. Here, we use a novel scale-free vertical tracking microscope (a.k.a. gravity machine; Krishnamurthy 2020 , 1040-1051 (doi:10.1038/s41592-020-0924-7)) to follow model sinking aggregates (agar spheres) with attached protists (), sinking over long distances while simultaneously measuring local flows. We find that activity due to attached causes significant changes to the flow around aggregates in a dynamic manner and reshapes mass transport boundary layers. Further, we find that activity-mediated local flows along with sinking modify the encounter and plume cross-sections of the aggregate and induce sustained aggregate rotations. Overall, our work shows the important role of biological activity in shaping the near-field flows around aggregates with potentially important effects on aggregate fate and material fluxes.
Topics: Seawater; Bacteria; Suspensions; Microscopy
PubMed: 36751929
DOI: 10.1098/rsif.2022.0537 -
Journal of the American Veterinary... Jun 2013To determine the concentration of doxycycline compounded from doxycycline hyclate tablets into liquid formulations for oral administration in veterinary species and...
OBJECTIVE
To determine the concentration of doxycycline compounded from doxycycline hyclate tablets into liquid formulations for oral administration in veterinary species and stored for 28 days.
DESIGN
Evaluation study.
SAMPLE
Doxycycline hyclate tablets (100 mg) crushed and mixed with a 50:50 mixture of syrup and suspension vehicles for oral administration to produce 3 batches each of 2 doxycycline formulations: 33.3 and 166.7 mg/mL.
PROCEDURES
Formulations were stored, protected from light, at room temperature (22° to 26°C [71.6° to 78.8°F]) and at a controlled cold temperature (refrigerated 2° to 8°C [35.6° to 46.4°F]). Doxycycline was extracted from the formulations, and concentration was measured by high-pressure liquid chromatography on days 0 (date of preparation), 1, 4, 7, 14, 21, and 28. Concentrations were compared with those of a US Pharmacopeial Convention reference standard. Formulation quality at each point was also assessed through color change, formulation consistency, and suspension uniformity.
RESULTS
On days 0, 1, 4, and 7, the concentration of each formulation was within 90% to 110% of the reference standard (range, 93% to 109%), which was deemed acceptable. However, doxycycline concentrations had decreased dramatically by day 14 and remained low for the duration of the study period. Doxycycline concentrations on days 14, 21, and 28 were all < 20% (range, 14% to 18%) of the reference standard, and the quality of the formulations decreased as well. No effect of storage temperatures on doxycycline concentration was identified.
CONCLUSIONS AND CLINICAL RELEVANCE
The concentration of doxycycline, compounded from commercial tablets in the vehicles evaluated to yield doses of 33.3 and 166.7 mg/mL, cannot be assured beyond 7 days.
Topics: Anti-Bacterial Agents; Chemistry, Pharmaceutical; Doxycycline; Drug Compounding; Drug Stability; Drug Storage; Suspensions; Time Factors; Veterinary Drugs
PubMed: 23725430
DOI: 10.2460/javma.242.12.1674 -
Yakugaku Zasshi : Journal of the... 2024The simple suspension method (SSM) involves administering tablets or capsules using a tube after disintegration and suspension in hot water without crushing or opening...
The simple suspension method (SSM) involves administering tablets or capsules using a tube after disintegration and suspension in hot water without crushing or opening the capsule. Particularly, for anticancer drugs, it is an excellent method of administration that reduces the risk of exposure during dispensing. In contrast, information on SSM for individual drugs is insufficient. Anticancer drugs present a therapeutic challenge because their information is limited. We investigated whether SSM is possible with 36 anticancer drugs. Furthermore, we examined the pH of the suspension of these drugs, for which no information on SSM is available. We found that suspension was possible for 24 of the 36 drugs. Furthermore, the pH of the suspension was measured, which provided important information when considering dissolution solutions other than hot water. Little changes in the pH were observed before or after passing through the tube. The results of this study may improve medication adherence in patients with cancer experiencing dysphagia.
Topics: Humans; Tablets; Suspensions; Water; Administration, Oral
PubMed: 38556318
DOI: 10.1248/yakushi.23-00194