Co-formulation of the rF1V plague vaccine with depot-formulated cytokines enhances immunogenicity and efficacy to elicit protective responses against aerosol challenge in mice.

This study evaluated a depot-formulated cytokine-based adjuvant to improve the efficacy of the recombinant F1V (rF1V) plague vaccine and examined the protective response following aerosol challenge in a murine model. The results of this study showed that co-formulation of the Alhydrogel-adsorbed rF1V plague fusion vaccine with the depot-formulated cytokines recombinant human interleukin 2 (rhuIL-2) and/or recombinant murine granulocyte macrophage colony-stimulating factor (rmGM-CSF) significantly enhances immunogenicity and significant protection at lower antigen doses against a lethal aerosol challenge. These results provide additional support for the co-application of the depot-formulated IL-2 and/or GM-CSF cytokines to enhance vaccine efficacy.

Label-Free Composition Analysis of Supramolecular Polymer-Nanoparticle Hydrogels by Reversed-Phase Liquid Chromatography Coupled with a Charged Aerosol Detector.

Supramolecular hydrogels formed through polymer-nanoparticle interactions are promising biocompatible materials for translational medicines. This class of hydrogels exhibits shear-thinning behavior and rapid recovery of mechanical properties, providing desirable attributes for formulating sprayable and injectable therapeutics. Characterization of hydrogel composition and loading of encapsulated drugs is critical to achieving the desired rheological behavior as well as tunable in vitro and in vivo payload release kinetics. However, quantitation of hydrogel composition is challenging due to material complexity, heterogeneity, high molecular weight, and the lack of chromophores. Here, we present a label-free approach to simultaneously determine hydrogel polymeric components and encapsulated payloads by coupling a reversed phase liquid chromatographic method with a charged aerosol detector (RPLC-CAD). The hydrogel studied consists of modified hydroxypropylmethylcellulose, self-assembled PEG-b-PLA nanoparticles, and a therapeutic compound, bimatoprost. The three components were resolved and quantitated using the RPLC-CAD method with a C4 stationary phase. The method demonstrated robust performance, applicability to alternative cargos (i.e., proteins) and was suitable for composition analysis as well as for evaluating in vitro release of cargos from the hydrogel. Moreover, this method can be used to monitor polymer degradation and material stability, which can be further elucidated by coupling the RPLC method with (1) a multi-angle light scattering detector (RPLC-MALS) or (2) high resolution mass spectrometry (RPLC-MS) and a Fourier-transform based deconvolution algorithm. We envision that this analytical strategy could be generalized to characterize critical quality attributes of other classes of supramolecular hydrogels, establish structure-property relationships, and provide rational design guidance in hydrogel drug product development.

Photooxidation-Initiated Aqueous-Phase Formation of Organic Peroxides: Delving into Formation Mechanisms.

Formation of highly oxygenated molecules (HOMs) such as organic peroxides (ROOR, ROOH, and H2O2) is known to degrade food and organic matter. Gas-phase unimolecular autoxidation and bimolecular RO2 + HO2/RO2 reactions are prominently renowned mechanisms associated with the formation of peroxides. However, the reaction pathways and conditions favoring the generation of peroxides in the aqueous phase need to be evaluated. Here, we identified bulk aqueous-phase ROOHs in varying organic precursors, including a laboratory model compound and monoterpene oxidation products. Our results show that formation of ROOHs is suppressed at enhanced oxidant concentrations but exhibits complex trends at elevated precursor concentrations. Furthermore, we observed an exponential increase in the yield of ROOHs when UV light with longer wavelengths was used in the experiment, comparing UVA, UVB, and UVC. Water-soluble organic compounds represent a significant fraction of ambient cloud-water components (up to 500 µM). Thus, the reaction pathways facilitating the formation of HOMs (i.e., ROOHs) during the aqueous-phase oxidation of water-soluble species add to the climate and health burden of atmospheric particulate matter.

Riboflavin based setup as an alternative method for a preliminary screening of face mask filtration efficiency.

Face masks are essential in reducing the transmission of respiratory infections and bacterial filtration efficiency, a key parameter of mask performances, requires the use of Staphylococcus aureus and specialised staff. This study aims to develop a novel method for a preliminary screening of masks or materials filtration efficiency by a green, easy and rapid setup based on the use of a riboflavin solution, a safe autofluorescent biomolecule. The proposed setup is composed of a commercial aerosol generator commonly used for aerosol therapy, custom 3D printed aerosol chamber and sample holder, a filter for downstream riboflavin detection and a vacuum pump. The filtration efficiency of four different masks was assessed using the riboflavin-based setup and the bacterial filtration efficiency (BFE). The averaged filtration efficiency values, measured with both methods, were similar but were higher for the riboflavin-based setup (about 2% for all tested samples) than bacterial filtration efficiency. Considering the good correlation, the riboflavin-based setup can be considered validated as an alternative method to bacterial filtration efficiency for masks and related materials fabrics filtration efficiency screening but This study aims to develop a novel method for a preliminary screening of masks or materials filtration efficiency by a green, easy and rapid setup based on the use of a riboflavin solution, a safe autofluorescent biomolecule, but not to replace regulation approaches. The proposed setup can be easily implemented at low price, is more rapid and eco-friendly and can be performed in chemical-physical laboratories without the needing of biosafety laboratory and specialised operators.

Developing Dry Powder Inhaler Formulations.

This section aims to provide a concise and contemporary technical perspective and reference resource covering dry powder inhaler (DPI) formulations. While DPI products are currently the leading inhaled products in terms of sales value, a number of confounding perspectives are presented to illustrate why they are considered surprisingly, and often frustratingly, poorly understood on a fundamental scientific level, and most challenging to design from first principles. At the core of this issue is the immense complexity of fine cohesive powder systems. This review emphasizes that the difficulty of successful DPI product development should not be underestimated and is best achieved with a well-coordinated team who respect the challenges and who work in parallel on device and formulation and with an appreciation of the handling environment faced by the patient. The general different DPI formulation types, which have evolved to address the challenges of aerosolizing fine cohesive drug-containing particles to create consistent and effective DPI products, are described. This section reviews the range of particle engineering processes that may produce micron-sized drug-containing particles and their subsequent assembly as either carrier-based or carrier-free compositions. The creation of such formulations is then discussed in the context of the material, bulk, interfacial and ultimately drug-delivery properties that are considered to affect formulation performance. A brief conclusion then considers the future DPI product choices, notably the issue of technology versus affordability in the evolving inhaler market.

Relative Humidity-Dependent Phase Transitions in Submicron Respiratory Aerosols.

Respiratory viruses, such as influenza and severe acute respiratory syndrome coronavirus 2, represent a substantial public health burden and are largely transmitted through respiratory droplets and aerosols. Environmental factors such as relative humidity (RH) and temperature impact virus transmission rates, and a precise mechanistic understanding of the connection between these environmental factors and virus transmission would improve efforts to mitigate respiratory disease transmission. Previous studies on supermicrometer particles observed RH-dependent phase transitions and linked particle phase state to virus viability. Phase transitions in atmospheric aerosols are dependent on size in the submicrometer range, and actual respiratory particles are expelled over a large size range, including submicrometer aerosols that can transmit diseases over long distances. Here, we directly investigated the phase transitions of submicrometer model respiratory aerosols. A probe molecule, Nile red, was added to particle systems including multiple mucin/salt mixtures, a growth medium, and simulated lung fluid. For each system, the polarity-dependent fluorescence emission was measured following RH conditioning. Notably, the fluorescence measurements of mucin/NaCl and Dulbecco's modified Eagle's medium particles indicated that liquid-liquid phase separation (LLPS) also occurs in submicron particles, suggesting that LLPS can also impact the viability of viruses in submicron particles and thus affect aerosol virus transmission. Furthermore, the utility of fluorescence-based measurements to study submicrometer respiratory particle physicochemical properties in situ is demonstrated.

Relevance of radon progeny measurements for the assessment of inhalation doses in groundwater utilities.

The high radon concentrations measured in the indoor air of groundwater facilities and the prevalence of the problem have been known for several years. Unlike in other workplaces, in groundwater plants, radon is released into the air from the water treatment processes. During the measurements of this study, the average radon concentrations varied from 500 to 8800 Bq m-3. In addition, the indoor air of the treatment plants is filtered and there are no significant internal aerosol sources. However, only a few published studies on groundwater plants have investigated the properties of the radon progeny aerosol, such as the equilibrium factor (F) or the size distribution of the aerosol, which are important for assessing the dose received by workers. Moreover, the International Commission on Radiological Protection has not provided generic aerosol parameter values for dose assessment in groundwater treatment facilities. In this study, radon and radon progeny measurements were carried out at three groundwater plants. The results indicate surprisingly high unattached fractions (fp= 0.27-0.58), suggesting a low aerosol concentration in indoor air. The correspondingFvalues were 0.09-0.42, well below those measured in previous studies. Based on a comparison of the effective dose rate calculations, either the determination of thefpor, with certain limitations, the measurement of radon is recommended. Dose rate calculation based on the potential alpha energy concentration alone proved unreliable.

Concern about the risk of aerosol contamination from ultrasonic scaler: a systematic review and meta-analysis.

BACKGROUND: Many instruments used in dentistry are rotary, such as handpieces, water syringes, and ultrasonic scalers that produce aerosols. The spray created by these instruments can carry, in addition to water, droplets of saliva, blood, and microorganisms, which can pose a risk of infections for healthcare professionals and patients. Due to the COVID-19 pandemic, this gained attention. OBJECTIVE: The aim was to carry out a systematic review of the evidence of the scope of the aerosol produced by ultrasonic scaler in environmental contamination and the influence of the use of intraoral suction reduction devices. DESIGN: Scientific literature was searched until June 19, 2021 in 6 databases: Pubmed, EMBASE, Web of science, Scopus, Virtual Health Library and Cochrane Library, without restrictions on language or publication date. Studies that evaluated the range of the aerosol produced by ultrasonic scaler during scaling/prophylaxis and the control of environmental contamination generated by it with the use of low (LVE) and high (HVE) volume evacuation systems were included. RESULTS: Of the 1893 potentially relevant articles, 5 of which were randomized controlled trials (RCTs). The meta-analysis of 3 RCTs showed that, even at different distances from the patient's oral cavity, there was a significant increase in airborne bacteria in the dental environment with the use of ultrasonic scaler. In contrast, when meta-analysis compared the use of HVE with LVE, there was no significant difference (P = 0.40/CI -0.71[-2.37, 0.95]) for aerosol produced in the environment. CONCLUSIONS: There is an increase in the concentration of bioaerosol in the dental environment during the use of ultrasonic scaler in scaling/prophylaxis, reaching up to 2 m away from the patient's mouth and the use of LVE, HVE or a combination of different devices, can be effective in reducing air contamination in the dental environment, with no important difference between different types of suction devices.

Size-resolved aerosol at a Coastal Great Lakes Site: Impacts of new particle formation and lake spray.

The quantification of aerosol size distributions is crucial for understanding the climate and health impacts of aerosols, validating models, and identifying aerosol sources. This work provides one of the first continuous measurements of aerosol size distribution from 1.02 to 8671 nm near the shore of Lake Michigan. The data were collected during the Lake Michigan Ozone Study (LMOS 2017), a comprehensive air quality measurement campaign in May and June 2017. The time-resolved (2-min) size distribution are reported herein alongside meteorology, remotely sensed data, gravimetric filters, and gas-phase variables. Mean concentrations of key aerosol parameters include PM2.5 (6.4 µg m-3), number from 1 to 3 nm (1.80x104 cm-3) and number greater than 3 nm (8x103 cm-3). During the field campaign, approximately half of days showed daytime ultrafine burst events, characterized by particle growth from sub 10 nm to 25-100 nm. A specific investigation of ultrafine lake spray aerosol was conducted due to enhanced ultrafine particles in onshore flows coupled with sustained wave breaking conditions during the campaign. Upon closer examination, the relationships between the size distribution, wind direction, wind speed, and wave height did not qualitatively support ultrafine particle production from lake spray aerosol; statistical analysis of particle number and wind speed also failed to show a relationship. The alternative hypothesis of enhanced ultrafine particles in onshore flow originating mainly from new particle formation activity is supported by multiple lines of evidence.

Emission and optical characteristics of brown carbon in size-segregated particles from three types of Chinese ships.

Brown carbon (BrC) is one of the important light absorption substances that have high light absorption ability under short wavelength light. However, limit studies have focused on the BrC emission from ships. In this study, size-segregated particulate matters (PM) were collected from three different types of ships, light absorption characteristics and size distribution of methanol-soluble BrC and water-soluble BrC in PM from ship exhausts were investigated. Results showed that four-stroke low-power diesel fishing boat (4-LDF) had the highest mass concentrations of methanol-soluble organic carbon (MSOC) and water-soluble organic carbon (WSOC), followed by 2-stroke high-power heavy-fuel-oil vessel (2-HHV), and four-stroke high-power marine-diesel vessel (4-HMV). While 2-HHV had obviously higher light absorption coefficients of methanol-soluble BrC (Abs365,M) and water-soluble BrC (Abs365,W) in unit weight of PM than the other two types of ships. The tested ships presented comparable or higher absorption efficiency of BrC in water extracts (MAE365,W) compared with other BrC emission sources. Majority of BrC was concentrated in fine particles, and the particle size distributions of both Abs365,M and Abs365,W showed bimodal patterns, peaking at 0.43-0.65 µm and 4.7-5.8 µm, respectively. However, different particle size distributions were found for MAE365,M between diesel and heavy fuel oil ships. Besides, different wavelength dependence in particles with different size were also detected. Ship exhaust could be confirmed as a non-ignorable BrC emission source, and complex influencing factor could affect the light absorption characteristics of ship emissions. Particle size should also be considered when light absorption ability of BrC was evaluated.

Efficacy and safety of visnadine in the treatment of symptoms of sexual dysfunction in heterosexual women: a systematic review of randomized clinical trials.

OBJECTIVE: To synthesize the primary evidence on the efficacy and safety of visnadine on symptoms of sexual dysfunction (SD) in heterosexual women. METHODS: We conducted a systematic review of randomized clinical trials (RCTs) with a primary search without language restriction in PubMed/Medline, Scopus, Embase, Web of Science, Cochrane Library, and international clinical trial registries. Trials reporting the use of visnadine by any route in women with SD were eligible. We performed screening, data extraction, and risk of bias assessment in a double-blind approach. The primary outcomes were the Female Sexual Function Index (FSFI) and its domains. Secondary outcomes were safety, arousal, lubrication, pleasure, orgasm, negative sensations, duration, and overall satisfaction. RESULTS: Initially, 242 records were retrieved. We selected nine papers for full-text reading and finally included two RCTs: one with a parallel design and one with a crossover design with a total of 96 patients. One study compared visnadine aerosol with a placebo, while the other compared different frequencies of visnadine aerosol use. Visnadine use showed a statistically significant improvement (p < 0.05) in overall FSFI scores, regardless of the frequency of use. A meta-analysis was not possible due to the high clinical and methodological heterogeneity between available studies. CONCLUSION: RCTs regarding the use of visnadine for the Female SD are scarce and methodologically limited. This preliminary evidence shows visnadine as a potentially effective and safe option to alleviate some of the clinical symptoms of SD in heterosexual women. However, future better-designed randomized studies with larger sample numbers are required.

Characteristics of second-hand exposure to aerosols from e-cigarettes: A literature review since 2010.

In recent years, the use of electronic vaping products (also named e-cigarettes) has increased due to their appealing flavors and nicotine delivery without the combustion of tobacco. Although the hazardous substances emitted by e-cigarettes are largely found to be much lower than combustible cigarettes, second-hand exposure to e-cigarette aerosols is not completely benign for bystanders. This work reviewed and synthesized findings on the second-hand exposure of aerosols from e-cigarettes and compared the results with those of the combustible cigarettes. In this review, different results were integrated based upon sampling locations such as residences, vehicles, offices, public places, and experimental exposure chambers. In addition, the factors that influence the second-hand exposure levels were identified by objectively reviewing and integrating the impacts of combustible cigarettes and e-cigarettes on the environment. It is a challenge to compare the literature data directly to assess the effect of smoking/vaping on the indoor environment. The room volume, indoor air exchange rate, puffing duration, and puffing numbers should be considered, which are important factors in determining the degree of pollution. Therefore, it is necessary to calculate the "emission rate" to normalize the concentration of pollutants emitted under various experimental conditions and make the results comparable. This review aims to increase the awareness regarding the harmful effects of the second-hand exposure to aerosols coming from the use of cigarettes and e-cigarettes, identify knowledge gaps, and provide a scientific basis for future policy interventions with regard to the regulation of smoking and vaping.

Characteristics of typical intermediate and semi volatile organic compounds in Shanghai during China International Import Expo event.

To ensure good air quality during the China International Import Expo (CIIE) event, stringent emission-reduction measures were implemented in Shanghai. To assess the efficacy of these measures, this study measured typical categories of intermediate/semi volatile organic compounds (I/SVOCs), including alkanes (C10-C26 n-alkanes and pristane), EPA-priority polycyclic aromatic hydrocarbons (PAHs), alkylnaphthalenes, benzothiazole (BTH) and chlorobenzenes (CBs), at an urban site of Shanghai before and during two CIIE events (2019 and 2020; non-CIIE versus CIIE). The average concentrations of alkanes and PAHs during both 2019 and 2020 CIIE events decreased by approximately 41% and 17%, respectively, compared to non-CIIE periods. However, the decline in BTH and CBs was only observed during CIIE-2019. Secondary organic aerosol (SOA) formation from alkanes, PAHs and BTH was evaluated under atmospheric conditions, revealing considerable SOA contributions from dimethylnaphthalenes and BTH. Positive matrix factorization (PMF) analysis further revealed that life-related sources, such as cooking and residential emissions, make a noticeable contribution (21.6%) in addition to the commonly concerned gasoline-vehicle sources (31.5%), diesel-related emissions (20.8%), industrial emissions (18.6%) and ship emissions (7.5%). These findings provide valuable insights into the efficacy of the implemented measures in reducing atmospheric I/SVOCs levels. Moreover, our results highlight the significance of exploring additional individual species of I/SVOCs and life-related sources for further research and policy development.

Human emissions of size-resolved fluorescent bioaerosols in control situations.

Human bioaerosols contribute significantly to indoor air quality. This study used a Wideband Integrated Bioaerosol Sensor (WIBS-4A) instrument for real-time measurement of particle size distribution and count to differentiate fluorescent bioaerosols from non-fluorescent aerosols. Through an experiment involving 12 subjects (six men and six women) wearing standard cotton clothing in a 2 m × 2 m × 2 m environmental chamber, we established a quantitative method to obtain the bioaerosol emission rate of a single subject, aiming to explore the effects of masks and sex on bioaerosol emissions from different individuals. The mean emission rates of fluorescent bioaerosols in the particle size ranges of 0.5-2.5 µm and 2.5-10 µm were 3.192±2.11×104 counts/(person·h) and 13.98±9.34×104 counts/(person·h), respectively. A comparison between those wearing and not wearing masks revealed no significant differences in the emissions of fluorescent bioaerosols. This suggests respiratory sources may not significantly impact the emissions of fluorescent bioaerosols from individuals under seated breathing conditions. Significant disparities in the fluorescent bioaerosol emission rates of different biological sexes were observed through independent sample analysis. Males exhibited 41 % and 15 % higher emission rates than females for particle size ranges of 0.5-2.5 µm and 2.5-10 µm, respectively, possibly because of different metabolic rates. A significant correlation between metabolic rates and fluorescent bioaerosols (sig = 0.044 < 0.05) was observed in all the subjects. These findings underscore the individual variations that affect bioaerosol emission rates. The data provided by this study will facilitate further analysis of the on-site measured data and source analysis.

Long-term effects of chronic exposure to electronic cigarette aerosol on the cardiovascular and pulmonary system in mice: A comparative study to cigarette smoke.

Electronic cigarettes (e-cigarettes) have rapidly gained popularity as alternatives to traditional combustible cigarettes. However, their long-term health impact remains uncertain. This study aimed to investigate the effects of chronic exposure to e-cigarette aerosol (ECA) in mice compared to conventional cigarette smoke (CS) exposure. The mice were exposed to air (control), low, medium, or high doses of ECA, or a reference CS dose orally and nasally for eight months. Various cardiovascular and pulmonary assessments have been conducted to determine the biological and prosthetic effects. Histopathological analysis was used to determine structural changes in the heart and lungs. Biological markers associated with fibrosis, inflammation, and oxidative stress were investigated. Cardiac proteomic analysis was applied to reveal the shared and unique protein expression changes in ECA and CS groups, which related to processes such as immune activation, lipid metabolism, and intracellular transport. Overall, chronic exposure to ECA led to adverse cardiovascular and pulmonary effects in mice, although they were less pronounced than those of CS exposure. This study provides evidence that e-cigarettes may be less harmful than combustible cigarettes for the long-term health of the cardiovascular and respiratory systems in mice. However, further human studies are needed to clarify the long-term health risks associated with e-cigarette use.

E-Cigarette Exposure Alters Neuroinflammation Gene and Protein Expression in a Murine Model: Insights from Perinatally Exposed Offspring and Post-Birth Mothers.

The use of E-cigarettes, often considered a safer alternative to traditional smoking, has been associated with high rates of cellular toxicity, genetic alterations, and inflammation. Neuroinflammatory impacts of cigarette smoking during pregnancy have been associated with increased risks of adverse childhood health outcomes; however, it is still relatively unknown if the same propensity is conferred on offspring by maternal vaping during gestation. Results from our previous mouse inhalation studies suggest such a connection. In this earlier study, pregnant C57BL/6 mice were exposed daily to inhaled E-cig aerosols (i.e., propylene glycol and vegetable glycerin, [PG/VG]), with or without nicotine (16 mg/mL) by whole-body inhalation throughout gestation (3 h/d; 5 d/week; total ~3-week) and continuing postnatally from post-natal day (PND) 4-21. As neuroinflammation is involved in the dysregulation of glucose homeostasis and weight gain, this study aimed to explore genes associated with these pathways in 1-mo.-old offspring (equivalent in humans to 12-18 years of age). Results in the offspring demonstrated a significant increase in glucose metabolism protein levels in both treatment groups compared to filtered air controls. Gene expression analysis in the hypothalamus of 1 mo. old offspring exposed perinatally to E-cig aerosols, with and without nicotine, revealed significantly increased gene expression changes in multiple genes associated with neuroinflammation. In a second proof-of-principal parallel study employing the same experimental design, we shifted our focus to the hippocampus of the postpartum mothers. We targeted the mRNA levels of several neurotrophic factors (NTFs) indicative of neuroinflammation. While there were suggestive changes in mRNA expression in this study, levels failed to reach statistical significance. These studies highlight the need for ongoing research on E-cig-induced alterations in neuroinflammatory pathways.

Review of the research status on the transmission and diffusion characteristics of indoor viral aerosol particles.

This study reviews the generation and diffusion characteristics of indoor viral aerosol particles, numerical simulation methods for the diffusion process of viral aerosols, and related research on the impact mechanism of different ventilation methods on the diffusion process of viral aerosols. Research has shown that the selection of initial conditions such as exhalation mode, initial airflow velocity, particle size, turbulence model, and calculation method for the generation of aerosol particles by the human body is of great significance for the numerical simulation of the diffusion process of viral aerosol particles. At the same time, on the basis of selecting appropriate ventilation methods, the reasonable setting of ventilation parameters (temperature, speed, height, etc.) can effectively suppress the spread of viral aerosols. This study can provide a theoretical basis for the study of related respiratory diseases, as well as technical and theoretical support for the selection of indoor ventilation methods to reduce the risk of human exposure caused by viral aerosols in the construction field. It also provides guidance and reference for aerosol transport and environmental protection in indoor atmospheric environments.

The Occupational and Environmental Hazards of Uncovered Toilets.

ABSTRACT: Substantial evidence demonstrates that plumes from uncovered toilets potentially expose nurses and other health care workers to aerosols containing infectious agents and hazardous drugs, including antineoplastic drugs. Most hospitals in the United States utilize flushometer-type toilets, which operate under high pressure and do not have a permanently attached closure or lid, which is known to reduce the aerosols generated by flushing. This article aims to raise awareness among nurses of the potential exposure risks associated with toilet plume aerosols, so they can educate other health care workers and take part in initiatives to address these risks.

Critical attributes of fine excipient materials in carrier-based dry powder inhalation formulations: The particle shape and surface properties.

The potential of fine excipient materials to improve the aerodynamic performance of carrier-based dry powder inhalation (DPI) formulations is well acknowledged but not fully elucidated. To improve the understanding of this potential, we studied two fine excipient materials: micronized lactose particles and silica microspheres. Inhalation formulations, each composed of a coarse lactose carrier, one of the two fine excipient materials (0.0-15.0 % w/w), and a spray-dried drug (fluticasone propionate) material (1.5 % w/w) were prepared. The physical structure, the flow behavior, the aerosolization behavior, and the aerodynamic performance of the formulations were studied. The two fine excipient materials similarly occupied carrier surface macropores. However, only the micronized lactose particles formed agglomerates and appeared to increase the tensile strength of the formulations. At 2.5 % w/w, the two fine excipient materials similarly improved drug dispersibility, whereas at higher concentrations, the micronized lactose material was more beneficial than the silica microspheres. The findings suggest that fine excipient materials improve drug dispersibility from carrier-based DPI formulations at low concentrations by filling carrier surface macropores and at high concentrations by forming agglomerates and/or enforcing fluidization. The study emphasizes critical attributes of fine excipient materials in carrier-based DPI formulations.

Ion Quantitation in Liposomal Products Using RP-HPLC with Charged Aerosol Detection.

Ion concentration in liposomal drugs is important for drug stability and drug release profile. However, quantifying ion concentration in liposomal drugs is challenging due to the absence of chromophores or fluorophores of ions and the efficiency of their release from the liposome structure. To address these issues, a method based on reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with a charged aerosol detector (CAD) has been developed to determine total, internal, and external ions in drug-loaded liposomal products. In this protocol, we focused on the quantitation of ammonium and sulfate ions in liposomal products, using generic PEGylated liposomal doxorubicin as an example. This method can be extended to calcium, acetate, and other ions in different liposomal formulations with slight modifications.