Hypothesis: Nanoscale characterisation of the self-associated species formed by amphiphilic pharmaceuticals in aqueous solution carries relevance across their entire journey from development through to manufacture - relevant, therefore, not only as regards formulation of the drug products as medicines, but also potentially relevant to their bioavailability, activity, and clinical side effects. Such knowledge and understanding, however, can only be fully secured by applying a range of experimental and theoretical methodologies.
Experiments: Herein, we apply a synergistic combination of solubility, surface tension, SANS, NMR and UV spectroscopic studies, together with MD simulation and QM calculations, to investigate the meso-structures of propranolol hydrochloride aggregates in bulk aqueous solutions, at concentrations spanning 2.
Background: Birthing on Country principles in Australia have seen a revitalisation in midwifery care over the last decade with it being seen as a metaphor for the best start to life for First Nations peoples. This scoping review aimed to explore the extent of evidence of Australian First Nations women's experiences of out-of-hospital childbirth and the alignment with Birthing on Country principles to inform paramedic practice.
Methods: Four databases were searched including MEDLINE, CINAHL, EBSCOhost Health and Scopus utilising the Joanna Briggs Institute (JBI) methodology for Scoping Reviews.
Lipid-based drug carriers are an attractive option to solubilise poorly water soluble therapeutics. Previously, we reported that the digestion of a short tail PC lipid (2C6PC) by the PLA2 enzyme has a significant effect on the structure and stability of the micelles it forms. Here, we studied the interactions of micelles of varying composition representing various degrees of digestion with a model ordered (70 mol% DPPC & 30 mol% cholesterol) and disordered (100% DOPC) lipid membrane.
View Article and Find Full Text PDFNanoparticle (NP) formulations are inherently polydisperse making their structural characterization and justification of specifications complex. It is essential, however, to gain an understanding of the physico-chemical properties that drive performance in vivo. To elucidate these properties, drug-containing poly(lactic acid) (PLA)-poly(ethylene glycol) (PEG) block polymeric NP formulations (or PNPs) were sub-divided into discrete size fractions and analyzed using a combination of advanced techniques, namely cryogenic transmission electron microscopy, small-angle neutron and X-ray scattering, nuclear magnetic resonance, and hard-energy X-ray photoelectron spectroscopy.
View Article and Find Full Text PDFThe interfacial structure and morphology of films spread from hyperbranched polyethylene imine/sodium dodecyl sulfate (PEI/SDS) aggregates at the air/water interface have been resolved for the first time with respect to polyelectrolyte charged density. A recently developed method to form efficient films from the dissociation of aggregates using a minimal quantity of materials is exploited as a step forward in enhancing understanding of the film properties with a view to their future use in technological applications. Interfacial techniques that resolve different time and length scales, namely, ellipsometry, Brewster angle microscopy, and neutron reflectometry, are used.
View Article and Find Full Text PDFWe demonstrate control of the structure and morphology of polypeptide/surfactant films at the air/water interface as a function of the maximum compression ratio of the surface area, exploiting a recently developed film formation mechanism that requires minimal quantities of materials involving the dissociation of aggregates. The systems studied are poly(L-lysine) (PLL) or poly(L-arginine) (PLA) with sodium dodecyl sulfate (SDS), chosen because the surfactant (i) interacts more strongly with the latter polypeptide due to the formation of hydrogen bonds between the guanidinium group and its oxygen atoms, and (ii) induces bulk β-sheet and α-helix conformations of the respective polypeptides. The working hypothesis is that such different interactions may be used to tune the film properties when compressed to form extended structures (ESs).
View Article and Find Full Text PDFA deep and detailed understanding of drug-dendrimer conjugates key properties is needed to define the critical quality attributes that affect drug product performance. The characterization must be executed both in the formulation media and in biological matrices. This, nevertheless, is challenging on account of a very limited number of suitable, established methods for characterizing the physicochemical properties, stability, and interaction with biological environment of complex drug-dendrimer conjugates.
View Article and Find Full Text PDFLipopolyplexes (LPDs) are of considerable interest for use as gene delivery vehicles. Here LPDs have been prepared from cationic vesicles (composed of a 1 : 1 molar ratio of DOTMA with the neutral helper lipid, DOPE), singly branched cationic peptides and plasmid DNA. All peptides contained a linker sequence (cleaved by endosomal furin) attached to a targeting sequence selected to bind human airway epithelial cells and mediate gene delivery.
View Article and Find Full Text PDFBackground: Work-integrated learning (WIL) in rural communities provides students with important learning opportunities while also providing a service to those communities. To optimise the potential benefits of work-integrated learning for health students and rural communities it is important to explore the practices and outcomes of these experiences.
Methods: This study used a qualitative research design underpinned by the theoretical framework of Theory of Practice Architectures to examine the way students learn during these placements.
The recent emergence of drug-dendrimer conjugates within pharmaceutical industry research and development introduces a range of challenges for analytical and measurement science. These molecules are very high molecular weight (100-200kDa) with a significant degree of structural complexity. The characteristics and quality attributes that require understanding and definition, and impact efficacy and safety, are diverse.
View Article and Find Full Text PDFMost research involving Aboriginal and Torres Strait Islander peoples has been conducted by non-Indigenous people and has not been a positive experience for many Aboriginal and Torres Strait Islander communities. This scoping review maps approaches to health research involving Aboriginal and Torres Strait Islander peoples and communities in Australia from the last two decades. A literature search found 198 papers, of which 34 studies met the inclusion criteria.
View Article and Find Full Text PDFReversible control of the 3D structure of polyelectrolyte/surfactant films at the air/water interface is showcased. A recently discovered mechanism is exploited to form highly efficient, stable and biocompatible films by spreading aggregates composed of poly-L-lysine and sodium dodecyl sulfate on the surface of water. Reversible control of: (1) the surface monolayer coverage, (2) the switching on or off discrete extended structures, and (3) the extended structure coverage is demonstrated for the first time.
View Article and Find Full Text PDFIntroduction: This study investigated differences between rural Australian First Nations and non-First Nations survey respondents' perceptions of COVID-19-related risks and analysed other variables that could predict an exacerbation of anxiety related to COVID-19 harms.
Methods: A cross-sectional online and paper survey of rural residents from the western regions of NSW, Australia, was conducted. Descriptive and multivariate statistical analyses were used to assess links between First Nations status and demographic measures including postcode, age, gender, education, rural or town/village location, proximity to medical services and living situation.
ACS Appl Mater Interfaces
July 2022
Lipid nanoparticles (LNPs) are important delivery systems for RNA-based therapeutics, yet the mechanism of their interaction with endosomal membranes remains unclear. Here, the interactions of nucleic acid-loaded LNPs that contain an ionizable lipid with models of the early and late endosomal membranes are studied, for the first time, using different reflectometry techniques. Novel insight is provided with respect to the subphase pH, the stage of the endosome, and the nature of the nucleic acid cargo.
View Article and Find Full Text PDFSurfactants are used in a wide range of chemical and biological applications, and for pharmaceutical purposes are frequently employed to enhance the solubility of poorly water soluble drugs. In this study, all-atom molecular dynamics (MD) simulations and small-angle neutron scattering (SANS) experiments have been used to investigate the drug solubilisation capabilities of the micelles that result from 10 wt% aqueous solutions of the non-ionic surfactant, Triton X-100 (TX-100). Specifically, we have investigated the solubilisation of saturation amounts of the sodium salts of two nonsteroidal anti-inflammatory drugs: ibuprofen and indomethacin.
View Article and Find Full Text PDFBiochim Biophys Acta Biomembr
June 2022
The stratum corneum's lipid matrix is a critical for the skin's barrier function and is primarily composed of ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). The lipids form a long periodicity phase (LPP), a unique trilayer unit cell structure. An enzyme driven pathway is implemented to synthesize these key lipids.
View Article and Find Full Text PDFPolyelectrolyte multilayers are promising drug carriers with potential applications in the delivery of poorly soluble drugs. Furthermore, the polyelectrolyte multilayer contributes towards electrostatic interactions, which enhances the physical and chemical stability of colloids when compared to those prepared by other approaches. The aim of this work was to generate a polyelectrolyte multilayer on well characterised nanoparticles of the poorly water-soluble drug, griseofulvin.
View Article and Find Full Text PDFJ Colloid Interface Sci
September 2021
Liquid lipid nanoparticles (LLN) are oil-in-water nanoemulsions of great interest in the delivery of hydrophobic drug molecules. They consist of a surfactant shell and a liquid lipid core. The small size of LLNs makes them difficult to study, yet a detailed understanding of their internal structure is vital in developing stable drug delivery vehicles (DDVs).
View Article and Find Full Text PDFAust J Rural Health
April 2021
Aims And Context: As a University Department of Rural Health, we have identified recurrent areas of service need among vulnerable rural populations, specifically the need for allied health. Concurrently, we have also identified missed opportunities for deliberate collaborative practice in rural clinical placements. This paper provides a commentary on our work in progress as we work to leverage available opportunities to provide both service from and education for health profession students on rural clinical placements.
View Article and Find Full Text PDFThis paper reports the first use of a novel completely optically based photothermal method (O-PTIR) for obtaining infrared spectra of both fixed and living cells using a quantum cascade laser (QCL) and optical parametric oscillator (OPO) laser as excitation sources, thus enabling all biologically relevant vibrations to be analyzed at submicron spatial resolution. In addition, infrared data acquisition is combined with concomitant Raman spectra from exactly the same excitation location, meaning the full vibrational profile of the cell can be obtained. The pancreatic cancer cell line MIA PaCa-2 and the breast cancer cell line MDA-MB-231 are used as model cells to demonstrate the capabilities of the new instrumentation.
View Article and Find Full Text PDFHypothesis: Biomimetic liquid crystalline systems are widely used in skin care cosmetics and topical pharmaceutical preparations. Our ability to rationally design such formulations, however, is hampered by our incomplete understanding of their structure on the nanoscale.
Experiments: Using polarized light microscopy and small-angle and wide-angle X-ray scattering, the molecular architecture and properties of a barrier formulation prepared from distearoylphosphatidylcholine mixed with long chain fatty acid and alcohols, with and without antimicrobial pentanediols are directly probed.
It is well-established that oil-in-water creams can be stabilised through the formation of lamellar liquid crystal structures in the continuous phase, achieved by adding (emulsifier) mixtures comprising surfactant(s) combined (of necessity) with one or more co-surfactants. There is little molecular-level understanding, however, of how the microstructure of a cream is modulated by changes in co-surfactant and of the ramifications of such changes on cream properties. We investigate here the molecular architectures of oil-free, ternary formulations of water and emulsifiers comprising sodium dodecyl sulfate and one or both of the co-surfactants hexadecanol and octadecanol, using microscopy, small-angle and wide-angle X-ray scattering and small-angle neutron scattering.
View Article and Find Full Text PDFThis study is about fine tuning the targeting capacity of peptide-decorated nanoparticles to discriminate between cells that express different integrin make-ups. Using microfluidic-assisted nanoprecipitation, we have prepared poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles with a PEGylated surface decorated with two different arginine-glycine-aspartic acid (RGD) peptides: one is cyclic (RGDFC) and has specific affinity towards αβ integrin heterodimers; the other is linear (RGDSP) and is reported to bind equally αβ and αβ. We have then evaluated the nanoparticle internalization in two cell lines with a markedly different integrin fingerprint: ovarian carcinoma A2780 (almost no αβ, moderate in αβ) and glioma U87MG (very high in αβ, moderate/high in αβ).
View Article and Find Full Text PDFUnderstanding the structure of the stratum corneum (SC) is essential to understand the skin barrier process. The long periodicity phase (LPP) is a unique trilayer lamellar structure located in the SC. Adjustments in the composition of the lipid matrix, as in many skin abnormalities, can have severe effects on the lipid organization and barrier function.
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