OUR ArchiveThe Otago University Research Archive digital repository system captures, stores, indexes, preserves, and distributes digital research material.https://ourarchive.otago.ac.nz:4432024-03-19T08:50:25Z2024-03-19T08:50:25ZTestable counterfactual equivalence in Two-Way Fixed-Effect designs: theory and practiceStirk-Wang, Leon Oyahttp://hdl.handle.net/10523/166522024-03-18T13:00:55Z2024-03-18T01:50:01ZTestable counterfactual equivalence in Two-Way Fixed-Effect designs: theory and practice
2024
Stirk-Wang, Leon Oya
Two-way fixed-effects (TWFE) designs are a popular identification strategy in the non-experimental program evaluation literature. The approach produces what are considered to be convincing causal effect estimates where the identifying assumptions hold. Unfortunately, the “parallel paths” assumption can be vulnerable to confounding that may not be detectable by pre-treatment trends tests and may not be controlled for through observable covariate adjustment. This dissertation proposes a testable condition that might replace the assumption of parallel paths in the context of location based confounders. It provides an outline of the circumstances where such a condition might be met; demonstrates how this condition may be used to recover the (joint) distribution of “unobservable” confounding variables; and quantifies the reduction in omitted variable bias.
Using the framework of matching as non-parametric control, this dissertation applies a machine learner (specifically a genetic algorithm) to the problem of estimating the (spatial) distribution of an “unobserved” confounder. In the first chapter, the performance of the method is evaluated in a series of simulations.
The latter chapters apply this method in two empirical contexts, estimating the size of natural hazard effects in residential real estate markets. These applications provide opportunities to compare results against conventional estimation procedures. They also provide opportunities to test the limitations of the method and discuss its value as a supplementary diagnostic tool.
The first empirical chapter finds that conventional estimation methods substantially underestimate the “true” effect of interest. Conventional estimates are anywhere from 12% to 70% smaller in size than the unconfounded effect depending on how those models are specified. This chapter suggests (and shows) that this underestimation may be explained by post-treatment confounding arising in the control observations. Controlling for the estimated distribution of the “unobserved” (spatial) confounder ensures that the control group is restricted to those observations with similar “location” characteristics.
The second finds that, despite having the appearance of an ideal natural experiment, compelling unconfounded location controls cannot be easily found. Consequently, estimates of the effect of interest should be interpreted with some additional caveats. The failure to converge on a convincing spatially confounding distribution is in itself a valuable piece of diagnostic information and is also discussed.
2024-03-18T01:50:01ZHunt for the Taro people: Investigations of microbotanical remains from N3/638 (north-western Motutangi Swamp, Aupōuri Peninsula), a former Māori wetland ditch-system.Benham, Rebecca Waikuinihttp://hdl.handle.net/10523/166512024-03-18T14:40:41Z2024-03-18T00:53:10ZHunt for the Taro people: Investigations of microbotanical remains from N3/638 (north-western Motutangi Swamp, Aupōuri Peninsula), a former Māori wetland ditch-system.
2023
Benham, Rebecca Waikuini
The northwestern margins of Motutangi Swamp, located on the Aupouri Peninsula in far-northern Aotearoa, incorporate several former wetland ditch systems below high dunes. Māori ancestors used these ditch systems during the early phase of human occupation in Aotearoa. Radiocarbon dates suggest an occupational period from (if not before) c. 1450 – c. 1700 CE. This thesis will analyse sediment samples from archaeological site N3/638 to investigate these ditch systems. Previous archaeobotanical research at Motutangi has identified starch comparable to kūmara (Ipomoea batatas), taro (Colocasia esculenta) and uwhi/yam (Dioscorea alata) (Horrocks and Barber, 2005, Horrocks et al., 2007b). These studies argue that both crops were productive in the marginally subtropical to warm-temperate climate of the Aupouri Peninsula tombolo. Succeeding publications have disputed the identification of taro remains at N3/638, arguing that the use of light microscopy to analyse microbotanical remains is not sufficient for a confident identification (Crowther, 2009b, Prebble et al., 2020). Calcium oxalate raphides, another type of taro evidence identified at N3/638, have also been critiqued because previous studies did not apply detailed morphometric analysis or utilize scanning electron microscopy (SEM). My thesis will address these critiques by implementing SEM analysis to analyse raphides from N3/638. My research examines starch and raphides extracted from soil deposits at Motutangi. By employing a combination of light microscopy and SEM analysis, this study critiques starch and raphides as diagnostic microbotanical elements at Motutangi. From the samples analysed, I have identified starch granules that are consistent with reference samples of D. alata and I. batatas, and starch amyloplasts and raphides comparable to Araceae, of which C. esculenta was the only Polynesian crop in precontact Aotearoa. SEM examination of archaeological soil samples shows raphides with diagnostic Araceae features including a long thin morphology, asymmetric terminations, and a median groove along two of the raphide’s opposite faces. Collectively and within the context of the variable microbotanical remains at Motutangi, this evidence supports the thesis that early Māori ancestors modified natural wetland environments during the early stages of Polynesian settlement to establish 3 the crop staples of tropical Polynesia, semiaquatic taro and dry soil uwhi, alongside kūmara, in the sub-tropical climate and fields of far-northern Aotearoa.
2024-03-18T00:53:10ZDrivers of population dynamics and fishery status of blackfoot pāua (Haliotis iris)Ryder, Finn Joelhttp://hdl.handle.net/10523/166502024-03-18T14:40:31Z2024-03-17T20:06:43ZDrivers of population dynamics and fishery status of blackfoot pāua (Haliotis iris)
2024
Ryder, Finn Joel
Drivers of coastal fishery status and population dynamics are complex due to the broad range of stressors to which coastal species are subjected. For successful fisheries management it is essential to understand drivers of population variability so that management can be adjusted accordingly. The population dynamics, and individual traits of abalone (Haliotids) can vary on the scale of metres to kilometres. In New Zealand, the cultural keystone, pāua (Haliotis iris, blackfoot abalone) has undergone considerable stock declines, and stock enhancement efforts have had limited success. For fisheries managers, it is important to know how a population of interest has changed over time, what factors may influence a populations spatial distribution and if they can use this information to adjust management. Therefore, the aim of this thesis is to disentangle drivers of fishery status and population dynamics of H. iris. First, I examined how a H. iris population in Peraki Bay, Banks Peninsula changed after 45 years. Comprehensive historic population data from the 1970s provided a baseline of abundance, size structure, and population dynamics before exposure to a commercial fishery and a range of environmental stressors. Repeat monitoring of the H. iris population at a 45-year interval indicate that a large change in population size and structure had occurred. Since 1976, there has been an 84% decrease in estimated population size. The remaining population is restricted to where juveniles were found in the original survey. This chapter indicates that H. iris may be susceptible to multiple stressors including habitat loss, climate change, and low and inconsistent recruitment. I then examined spatial drivers of H. iris density and shell length using multiple regression modelling, and generalised linear modelling. Physical and biological habitat and fishing restrictions data were gathered across six Customary fishery Protection Areas (CPAs, Mātaitai Reserves and Taiāpure Local Fisheries) across the takiwā (tribal area) of the Te Waipounamu (South Island) iwi (tribe) Ngāi Tahu. Model averaging indicate that H. iris density and size are driven by different factors. Haliotis iris density was negatively correlated to time under fishing restrictions, and macroalgal density. Shell length of H. iris was larger in deep habitats and negatively related to the density of the gastropod, Cookia sulcata. Spatial drivers were then investigated further in the East Otago Taiāpure (EOT), a CPA in southern Te Waipounamu. In-situ and modelled wave data, and drift algae biomass were used to determine whether H. iris reach higher densities and larger shell lengths in more wave exposed environments. Principal component regression and bootstrapping indicate that H. iris density was positively related to wave bottom orbital velocity, but negatively related to days exposed to large wave events. No relationship was observed between drift algae biomass and density or mean shell length of H. iris. Lastly, I investigated the depth distribution of H. iris in the EOT in light of a proposal by the EOT Management Committee to harvest H. iris at wading depths. Wading-only harvest involves gathering in shallow waters (depths up to around knee deep) without the use of a mask and snorkel. The reasoning behind the proposal being that a wading-only fishery could keep the fishery open while providing protection for populations in deeper water. The abundance and shell length of H. iris were recorded at 0.1 m depth intervals using belt transects. Provided a wadable limit of 0.5 metres is set, 78% of the H. iris surveyed would be accessible to wading harvest at chart datum, although this percentage differed among sites from 55 – 99%. Shell length increased with depth, indicating that a depth refuge would provide protection to mature individuals. This study indicates that some sites may be suited to wading harvest while others may not, highlighting the need to consider the reef by reef implications of management decisions.
Overall, this thesis provides new insights on how H. iris populations can change on long timescales and small spatial scales. This information, can be used to make more informed management decisions for H. iris, on ecologically relevant scales, in New Zealand. The environmental drivers discussed throughout this thesis however, will likely apply to other abalone species, and may be useful to guide management decisions and restoration efforts in other abalone fisheries globally.
2024-03-17T20:06:43ZProfiling free amino acid pool in the muscles of triplefin-fish after being fed with chitosan and zein-based films containing heavy metals to identify the potential changes in amino acid metabolismZhao, Chunhttp://hdl.handle.net/10523/166492024-03-15T02:43:46Z2024-03-15T02:43:46ZProfiling free amino acid pool in the muscles of triplefin-fish after being fed with chitosan and zein-based films containing heavy metals to identify the potential changes in amino acid metabolism
2024
Zhao, Chun
Previous studies have demonstrated that plastic particles (PLA), degraded from food packaging waste, have high affinity with heavy metals (HM) that result in a worse combined marine plastic pollution than plastic pollution alone. Chitosan and zein-based edible food film (CZF) is biodegradable and environmentally friendly which could be considered as an alternative material to reduce the plastic pollution. On the other hand, the heavy metals bound to PLA could induce oxidative stress disrupting the amino acid metabolism of fish, hence there is a need to evaluate whether CZF can reduce the heavy metal complex formation as well as the resulting oxidative stress that affects the amino acid metabolism of fish. The heavy metals came from the contaminants originally present in the ingredients used in the film making.
For this study, Triplefin-fish (Forsterygion capito, TPN-fish), a local species found in New Zealand waters was selected as our model organism due to its integral role within marine ecosystems, particularly in contributing to the lower levels of marine food chains. We exposed them to PLA and CZF at similar dosage and frequency for the same predefined feeding time (39 days). The profile of amino acid pool was measured only in the muscle portion of the fish. Based on the literature review, analysis of the free amino acid (FAA) pool was selected as a key biomarker to evaluate the effects of CZF and PLA exposure on TPN-fish muscle. The FAA pool profiling was conducted using gas chromatography with flame ionization detector (GC- FID) as an analytical approach. Multivariate and univariate statistical approaches, namely principal component analysis (PCA) and orthogonal partial least squares–discriminant analysis (OPLS-DA), and Mann–Whitney U test and one-way analysis of variance (ANOVA), were used to identify FAA discriminators associated with exposure to CZF and PLA. The identified discriminators were further evaluated by pathway analysis to identify potentially affected areas of amino acid metabolism.
The FAA pool in the white muscle of TPN-fish exposed to CZF was found to be altered, including a decreased level of branched chain amino acids (BCAAs), serine, methionine, phenylalanine, histidine, tyrosine, tryptophan, ornithine, and an increased level of alanine and glutamine. In addition, specific impacted pathways were identified in relation to the change in the FAA pool, namely phenylalanine, tyrosine and tryptophan biosynthesis; alanine, aspartate, glutamic acid and glutamine metabolism; valine, leucine and isoleucine biosynthesis. Overall, the altered amino acid metabolism was attributed to abnormal energy metabolism, reduction of weight gain and a disturbed immune system in TPN-fish. Moreover, the decreased levels of phenylalanine, tryptophan and histidine were found to be associated with changes in fish behaviour and swimming performance. The present study has demonstrated that FAA pool profiling can be a robust and effective approach in monitoring the biophysical effects of exposing TPN-fish to CZF.
This study was the first to use GC-FID based FAA pool profiling to investigate the effect of an alternative food packaging material (CZF) in a New Zealand aquatic ecosystem. Evaluation of the FAA data indicated that this approach could specifically contribute to the evaluation of the safety of CZF in the environment. The results of the present study also provide a preliminary framework in relation to the application of FAA profiling to evaluate metabolic changes in a model organism, on exposure to an alternative food packaging material, and its potential effect on the environment.
2024-03-15T02:43:46ZImmune cell activation and function in Crohn's diseaseLaws, Gemma Ashleighhttp://hdl.handle.net/10523/166482024-03-18T14:41:03Z2024-03-15T01:27:46ZImmune cell activation and function in Crohn's disease
2024
Laws, Gemma Ashleigh
Crohn’s disease (CD) is a chronic inflammatory bowel disease with many contributing factors: the immune response, genetic susceptibility, environmental factors, intestinal epithelium, and the host microbiome. Current treatments aim to control excessive inflammation but are not always effective. Human intestinal organoids can be grown from patient intestinal biopsy stem cells and can be used in in vitro experimental models to account for patient heterogeneity when investigating the pathogenesis of CD. I developed a two-dimensional (2D) intestinal organoid monolayer transwell model that corresponds to the lumen and lamina propria of the human gut. The monolayer model was used to manipulate apical (lumen) and basal (lamina propria) compartments with the addition of commensal bacteria and patient-matched peripheral blood mononuclear cells (PBMCs), respectively, and to study the contribution of the immune response on the epithelial integrity.
Using these 2D human intestinal organoids, I modelled the gut immune responses in people with CD compared to healthy controls (HC), as well as the effect of bacteria and immune cells from the same patient on the epithelial integrity of the monolayers. Addition of PBMCs and heat killed bacteria to CD monolayers resulted in reduced epithelial resistance compared to monolayers derived from HC donors.
I developed a model of inflammation using HC monolayers and polyclonally active immune cells. The degree of immune cell activation was correlated with reduced epithelial integrity. Epithelial integrity was restored with the addition of anti-tumour necrosis factor (TNF) antibody in all HC derived monolayers and some CD derived monolayers (responders) and this response was associated with reduced abundance of CD4 and CD8 T cells and reduced inflammatory cytokine (TNF and interferon (IFN)-γ) production.
CD is associated with microbial dysbiosis and probiotic use has been an attractive therapeutic option to alter the microbiota in patients with CD. In this thesis, I developed a co-culture of human organoid monolayers, autologous immune cells and live probiotic bacteria. The influence of live probiotic bacteria on cytokine production, PBMCs phenotypes and epithelial integrity in the inflammation model was investigated. Addition of either the live probiotics Escherichia coli Nissle 1917 (EcN) or Vivomixx restored epithelial integrity in only some HC and CD derived monolayers, and affected the expression and localisation of tight junction proteins. Epithelial protection mediated by addition of probiotics was associated with reduced inflammatory immune cell phenotypes and reduced TNF and IFN-g cytokine production.
Taken together, activated immune cells caused inflammatory mediated epithelial damage to human organoid monolayers, and epithelial protection by anti-TNF or probiotic bacteria was associated with reduced abundance of T cells populations and decreased concentrations of TNF and IFN-γ, suggesting that epithelial damage in CD is the result of these inflammatory cytokines. Investigating the interaction of gut bacteria, immune cells and the intestinal epithelial cells will help in understanding the pathogenesis of CD. This organoid model, which is derived from individual patient tissues, accounts for patient heterogeneity and leads towards a personalised medicine approach.
2024-03-15T01:27:46ZFire & Ice Using ancient DNA to reconstruct the phylogeography of the extinct New Zealand Goose Cnemiornis spp. Te Ahi me te Hukapapa Te matai whenua ā-ira o te TarepoGreer, Liamhttp://hdl.handle.net/10523/166472024-03-18T14:40:17Z2024-03-15T01:17:48ZFire & Ice Using ancient DNA to reconstruct the phylogeography of the extinct New Zealand Goose Cnemiornis spp. Te Ahi me te Hukapapa Te matai whenua ā-ira o te Tarepo
2024
Greer, Liam
Changes in the physical environment over time has a sustained impact on the physical and genetic features of taxa and populations within a species. New Zealand has had a long and varied history in its 80-million-year existence which has shaped the endemic and native biota that call it home. The recent field of Palaeogenomics has shed light on the complex ways that the changes in the environment have impacted those species. The New Zealand goose Cnemiornis is a genus of recently extinct large and flightless waterfowl which was previously resident on both two main islands in the archipelago: Cnemiornis gracilis on the North Island, and Cnemiornis calcitrans on the South Island. In this thesis, palaeogenetic approaches were used to sample the DNA of Cnemiornis and construct the phylogeographic history and structure of the genus, examining whether the genus has been impacted by geologic events in patterns like those observed in cohabitant avifauna. Recovered partial mitogenomes confirmed the placement of Cnemiornis within the Anatidae family as the sister taxon to the extant Cape Barren goose Cereopsis novaehollandiae. Strong support for the existence of two species of Cnemiornis was shown through phylogenetic analysis, indicating that the two species diverged in the Mid Pleistocene as a result of the closure of the Manawatū strait. Within the South Island species C. calcitrans, phylogenetic analysis found strong support for two genetically distinct clades, called here C. calcitrans “northern” and C. calcitrans “southern”, with divergence attributed to the glacial-interglacial cycles of glacier expansion and contraction in the Southern Alps, and the Mid Pleistocene climate transition (MPCT). Within the North Island species, evidence thought limited was found to support two clades called here C. gracilis “eastern” and C. gracilis “western”, with divergence attributed to the intermittent volcanic events of the Taupō Volcanic Zone in central North Island. This study represents the first in-depth examination of a previously little known extinct New Zealand genus and furthers the evidence for palaeogenomics as a significant tool in the understanding of how a changing world impacts living organisms.
2024-03-15T01:17:48ZOn the orientation of the soul toward grace or God: Simone Weil and Robert BressonVoigt Hogg, Vida Virginia Gertrudehttp://hdl.handle.net/10523/166462024-03-15T00:37:36Z2024-03-15T00:37:36ZOn the orientation of the soul toward grace or God: Simone Weil and Robert Bresson
2024
Voigt Hogg, Vida Virginia Gertrude
This thesis analyses and compares the religious and metaphysical philosophy of Simone Weil (1909-1943) with the cinema of auteur director, Robert Bresson (1901-1999), especially, in relation to their mutual concern regarding the soul in affliction. I argue that by understanding the contribution of Weil and Bresson, this knowledge may assist in learning that attention toward the soul will help to transcend the force of affliction experienced in one’s life. The methodological framework is based on Weil’s philosophical concepts, in particular, attachment, detachment, attention, affliction, decreation, necessity, and justice. I elucidate these concepts through the analysis of a select group of Bresson’s films. In my exploration, I show that in the cinematograph, Bresson’s approach converges with Weil’s philosophy as far as the natural (necessity) and the supernatural (divine grace) or God’s love are concerned. The analysis of specific scenes demonstrates Bresson’s emphasis on reality (the supernatural, as opposed to unreality or the natural), divination, and automatism, to reveal the force of affliction Weil asks us to transcend by way of attention. I suggest that Weil’s philosophy is a conscious practice which can be adapted to each individual soul. Here I draw on my experience of affliction, in addition to Bresson’s protagonists, Saint Augustine’s The Confessions, the BCE Hindu Scripture: The Bhagavad Gītā, and Homer’s Iliad or The Poem of Force; also, Plato’s “Allegory of the Cave” and the “Great Beast” in the Republic. This thesis argues that while the protagonists in Bresson’s films may be taken as figures for one or other of Weil’s concepts, the latter must be considered as “progressive,” namely: as each concept is first learned and then practiced, the soul only thus is reoriented to move closer toward its reunion with God, the creator.
2024-03-15T00:37:36ZInhaled dry powder to treat respiratory infectionsSaha, Tusharhttp://hdl.handle.net/10523/166452024-03-14T00:25:51Z2024-03-14T00:25:51ZInhaled dry powder to treat respiratory infections
2024
Saha, Tushar
Background: A number of viral and bacterial pathogens are responsible for multiple respiratory diseases in humans. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most recent example of the significant global health burden related to these infectious diseases. Although numerous antibacterial and antiviral treatments are available, not all of them are effective at rapidly achieving the desired therapeutic outcomes when administered in their conventional dosage forms such as tablets, capsules, or injections. The key limitations include numerous side effects due to the administration of high doses and insufficient drug concentration in the respiratory tract, the primary target site of many of these infections. Alternatively, inhaled treatment is considered an efficient approach for treating infections like SARS-CoV-2, by supporting the administration of lower doses and ensuring higher concentrations of the drug(s) in the lung. The inhaled treatment combining two or more anti-infective agents can increase potency and reduce the possibility of drug resistance. Repurposed drugs are often chosen against these respiratory pathogens and during pandemic situations as they are readily available and require less time to develop. Subsequently, this thesis aimed to develop both single and combinational inhalable dry powders containing suitable repurposed agents having anti-infective properties, mainly targeting viral respiratory pathogens, such as SARS-CoV-2, while also evaluating their effectiveness against selected bacterial respiratory pathogens (Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Klebsiella pneumoniae).
Methods: Early in the COVID-19 pandemic when limited options were available to target SARS-CoV-2, four commercially available and repurposed drugs having anti-infective properties, namely ivermectin, remdesivir, disulfiram, and ebselen were selected to develop as inhalable dry powders. Ivermectin and ebselen were developed as a single drug containing dry powder. On the other hand, remdesivir was developed as a combination with disulfiram or ebselen due to their reported synergistic activity. The inhalable dry powders were prepared by spray drying technique and in the presence/absence of different amino acids such as L-leucine, L-methionine, and L-tryptophan. The prepared dry powders were characterized using scanning electron microscopy (SEM), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy to assess the dry powder morphology and particle size, residual solvent amount, crystallinity, and drug-drug/drug-excipient interactions. The stability of ivermectin and remdesivir-disulfiram combinational dry powders was assessed at 25 °C/<15% RH and 25 °C/53% RH conditions for one month. The cytotoxicity and anti-SARS-CoV-2 activity of ivermectin dry powder and combinational dry powders of remdesivir with disulfiram/ebselen were assessed in vitro using cultured human airway epithelial cells (Calu-3 cells). In addition, the cytotoxicity and antimicrobial activity of ebselen dry powders were assessed using an alveolar epithelial cell line (A549 cells) and against Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa and Klebsiella pneumoniae.
Results: All the prepared dry powders were within the size range of 1–5 μm indicating their suitability for inhalation. The used raw materials were crystalline in nature. However, the spray-dried ivermectin dry powder was amorphous whereas the other formulations such as ebselen dry powders, remdesivir-disulfiram, and remdesivir-ebselen combinational dry powders remained crystalline. The residual solvent amount was ~1% (w/w) for all the dry powders, and no drug-drug/drug-excipient interactions were observed. Different drugs showed distinct morphological features after spray drying. The optimized ivermectin and ebselen dry powders were wrinkled whereas remdesivir-disulfiram and remdesivir-ebselen combinational dry powders were spherical. The average fine particle fraction of optimized ivermectin, remdesivir-disulfiram combination, remdesivir-ebselen combination, and ebselen dry powders were 83%, 61%, 65%, and 68%, respectively. All these optimized dry powders contained L-leucine as an excipient. The stability study conducted for ivermectin and remdesivir-disulfiram combinational dry powders revealed no significant difference in the physicochemical and in vitro aerosolization properties of the respective dry powders. The 50% cytotoxic concentration (CC50) values of the optimized ivermectin, remdesivir-disulfiram combination, and remdesivir-ebselen combinational dry powders were 39.1 μM, 41.51 μM and >100 μM, respectively. The half maximal inhibitory concentration (IC50) of optimized ebselen dry powder was 225 μg/mL tested in A549 cells. All the dry powders showed comparable anti-infective and antimicrobial activity to the raw drugs. The half maximal effective concentration (EC50) of the ivermectin, remdesivir-disulfiram combination, and remdesivir-ebselen dry powders against SARS-CoV-2 were 15.8 μM, 4.43 μM, and 8.04 μM, respectively. In addition, the ebselen dry powders showed potent antimicrobial effects against Gram-positive bacteria Staphylococcus aureus and Streptococcus pneumoniae with a low minimum inhibitory concentration (MIC) of 0.31 μg/mL and 0.16 μg/mL, respectively. However, the dry powders lacked potent antimicrobial activity against the Gram-negative pathogens Pseudomonas aeruginosa and Klebsiella pneumoniae. It is important to highlight that all the cellular toxicity (CC50 and IC50) and anti-infective as well as the antimicrobial (EC50 and MIC) values for the dry inhalable formulations were comparable to those obtained with respective non-formulated drugs.
Conclusions: The stable inhalable dry powders containing single and combinational antimicrobial agents were successfully developed by spray drying technique. L-leucine-containing dry powders showed better aerosolization properties compared to the L-leucine-free formulations or other amino acids. More importantly, the potency of all the prepared dry powders remained comparable to the raw active agents, with the dry powders showing limited cell toxicity in the respiratory cell lines used in this study. Further preclinical studies in animal models (e.g., humanized mice, African green monkeys) will test the suitability of the prepared dry powders to inhibit SARS-CoV-2, Staphylococcus aureus and Streptococcus pneumoniae.
2024-03-14T00:25:51Z