Dataset Information

Pulmonary Inhalation of Biotherapeutics: A Systematic Approach to Understanding the Effects of Atomisation Gas Flow Rate on Particle Physiochemical Properties and Retained Bioactivity.

ABSTRACT: The identification of spray-drying processing parameters capable of producing particles suitable for pulmonary inhalation with retained bioactivity underpins the development of inhalable biotherapeutics. Effective delivery of biopharmaceuticals via pulmonary delivery routes such as dry powder inhalation (DPI) requires developing techniques that engineer particles to well-defined target profiles while simultaneously minimising protein denaturation. This study examines the simultaneous effects of atomisation gas flow rate on particle properties and retained bioactivity for the model biopharmaceutical lysozyme. The results show that optimising the interplay between atomisation gas flow rate and excipient concentration enables the production of free-flowing powder with retained bioactivity approaching 100%, moisture content below 4%, and D₅₀ < 4 µm, at yields exceeding 50%. The developed methodologies inform the future design of protein-specific spray-drying parameters for inhalable biotherapeutics.

SUBMITTER: Foley L

PROVIDER: S-EPMC11359500 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Pulmonary Inhalation of Biotherapeutics: A Systematic Approach to Understanding the Effects of Atomisation Gas Flow Rate on Particle Physiochemical Properties and Retained Bioactivity.

Foley Laura L Ziaee Ahmad A Walker Gavin G O'Reilly Emmet E

Pharmaceutics 20240801 8

The identification of spray-drying processing parameters capable of producing particles suitable for pulmonary inhalation with retained bioactivity underpins the development of inhalable biotherapeutics. Effective delivery of biopharmaceuticals via pulmonary delivery routes such as dry powder inhalation (DPI) requires developing techniques that engineer particles to well-defined target profiles while simultaneously minimising protein denaturation. This study examines the simultaneous effects of ...[more]

PMID: 39204365

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Project description:Particle inhalation rate (PIR) is an air pollution exposure metric that relies on age-, sex-, and physical activity-specific estimates of minute respiratory volume (MRV; L/min-kg) to account for personal inhalation patterns. United States Environmental Protection Agency (USEPA)-generated MRV estimates derive primarily from relatively homogenous populations without substantial cardiorespiratory challenges. To determine if these MRV estimates are relevant to populations in generally poor cardiorespiratory health (e.g., the Boston Puerto Rican Health Study (BPRHS) population) or whether population-specific estimates are needed, we 1) estimated population-specific MRVs and compared them to USEPA MRV estimates, and 2) compared exposure distributions and health effect estimates using PIR with population-specific MRVs, PIR with USEPA MRVs, and ambient particle number concentration (PNC). We recruited 40 adults (80% Puerto Rican, mean age = 60.2 years) in Boston with health characteristics similar to the BPRHS population. We measured pulse, oxygen saturation, respiration rate, and inspiratory volume while participants walked, stood, sat, and lay down. Pulse, respiration rate, inspiratory volume, and MRV were greater when participants were walking/standing compared to sitting or lying down. We then calculated MRVs adjusted for age, sex, measured body weight, and physical activity using data from 19 Puerto Rican participants who wore a nose clip or held their nostrils closed. We applied the population-specific and USEPA MRVs to estimate ultrafine particle exposure for participants in the BPRHS (n = 781). We compared exposure distributions and health effect estimates using the PIR with population-specific MRV estimates, PIR with USEPA MRV estimates, and ambient concentrations. We found that while population-specific MRVs differed from USEPA MRVs, particularly for unhealthy participants, PIR exposure distributions and health effect estimates were similar using each exposure metric. Confidence intervals were narrower using the PIR metrics than ambient PNC, suggesting increased statistical efficiency. Even in our understudied population, using USEPA MRVs did not meaningfully change PIR estimates.

Project description:BackgroundAn important aspect of nanomaterial (NM) risk assessment is establishing relationships between physicochemical properties and key events governing the toxicological pathway leading to adverse outcomes. The difficulty of NM grouping can be simplified if the most toxicologically relevant dose metric is used to assess the toxicological dose-response. Here, we thoroughly investigated the relationship between acute and chronic inflammation (based on polymorphonuclear neutrophil influx (% PMN) in lung bronchoalveolar lavage) and the retained surface area in the lung. Inhalation studies were performed in rats with three classes of NMs: titanium dioxides (TiO2) and carbon blacks (CB) as poorly soluble particles of low toxicity (PSLT), and multiwall carbon nanotubes (MWCNTs). We compared our results to published data from nearly 30 rigorously selected articles.ResultsThis analysis combined data specially generated for this work on three benchmark materials - TiO2 P25, the CB Printex-90 and the MWCNT MWNT-7 - following subacute (4-week) inhalation with published data relating to acute (1-week) to subchronic (13-week) inhalation exposure to the classes of NMs considered. Short and long post-exposure recovery times (immediately after exposure up to more than 6 months) allowed us to examine both acute and chronic inflammation. A dose-response relationship across short-term and long-term studies was revealed linking pulmonary retained surface area dose (measured or estimated) and % PMN. This relationship takes the form of sigmoid curves, and is independent of the post-exposure time. Curve fitting equations depended on the class of NM considered, and sometimes on the duration of exposure. Based on retained surface area, long and thick MWCNTs (few hundred nm long with an aspect ratio greater than 25) had a higher inflammatory potency with 5 cm2/g lung sufficient to trigger an inflammatory response (at 6% PMN), whereas retained surfaces greater than 150 cm2/g lung were required for PSLT.ConclusionsRetained surface area is a useful metric for hazard grouping purposes. This metric would apply to both micrometric and nanometric materials, and could obviate the need for direct measurement in the lung. Indeed, it could alternatively be estimated from dosimetry models using the aerosol parameters (rigorously determined following a well-defined aerosol characterization strategy).

Dataset Information

Pulmonary Inhalation of Biotherapeutics: A Systematic Approach to Understanding the Effects of Atomisation Gas Flow Rate on Particle Physiochemical Properties and Retained Bioactivity.

Publications

Pulmonary Inhalation of Biotherapeutics: A Systematic Approach to Understanding the Effects of Atomisation Gas Flow Rate on Particle Physiochemical Properties and Retained Bioactivity.

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