Pulmonary drug delivery via microspheres has gained growing interest as a noninvasive method for therapy. However, drug delivery through the lungs via inhalation faces great challenges due to the natural defense mechanisms of the respiratory tract, such as the removal or deactivation of drugs. This study aims to develop a natural polymer-based microsphere system with a diameter of around 3 μm for encapsulating pulmonary drugs and facilitating their delivery to the deep lungs. Pectin was chosen as the foundational material due to its biocompatibility and degradability in physiological environments. Electrospray was used to produce the pectin-based hydrogel microspheres, and Design-Expert software was used to optimize the production process for microsphere size and uniformity. The optimized conditions were determined to be as follows: pectin/PEO ratio of 3:1, voltage of 14.4 kV, distance of 18.2 cm, and flow rate of 0.95 mL/h. The stability and responsiveness of the pectin-based hydrogel microspheres can be altered through coatings such as gelatin. Furthermore, the potential of the microspheres for pulmonary drug delivery (i.e., their responsiveness to the deep lung environment) was investigated. Successfully coated microspheres with 0.75% gelatin in 0.3 M mannitol exhibited improved stability while retaining high responsiveness in the simulated lung fluid (Gamble's solution). A gelatin-coated pectin-based microsphere system was developed, which could potentially be used for targeted drug delivery to reach the deep lungs and rapid release of the drug.
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http://dx.doi.org/10.3390/gels9090707 | DOI Listing |
Background: The hyperphosphorylation, mislocalization, and aggregation of the microtubule associated protein Tau (MAPT) is a driving force in tauopathies, a group of progressive, neurodegenerative disorders. These pathogenic intracellular aggregates, known as neurofibrillary tangles (NFTs), are a hallmark in several diseases such as frontotemporal dementia, progressive supranuclear palsy, and Alzheimer's Disease. While anti-Tau immunotherapies emphasize the clearance of extracellular Tau aggregates, they do not address the intracellular accumulation of NFTs.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Université de Lille, Lille, Hauts-de-France, France.
Background: Tau proteins aggregate in a number of neurodegenerative disorders known as tauopathies. Various studies have highlighted the role of microtubule-binding domains in the intracellular aggregation of Tau protein.
Method: Using a library of synthetic VHHs humanized in collaboration with Hybrigenics, we have developed a number of anti-tau VHHs.
Alzheimers Dement
December 2024
Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, NSW, Australia.
Background: Alzheimer's Disease (AD) poses a substantial global health burden, necessitating innovative therapeutic strategies. This study investigates the neuroprotective potential of a chrysin-loaded Nanostructured Lipid Carrier (NLC) drug delivery system in AD management. Employing the high-pressure homogenization method, chrysin-loaded NLCs were meticulously formulated to optimize drug delivery efficiency.
View Article and Find Full Text PDFBackground: Previously, we demonstrated therapeutic benefits following intraperitoneal delivery of the TGR5 agonist HY209 in 5xFAD, a transgenic mouse model of Alzheimer's Disease (AD). Given the desirability of a more acceptable administration route for prolonged AD treatment, we assessed the efficacy of HY209 via oral delivery. This study aims to elucidate the therapeutic potential of NuCerin, an oral formulation of HY209, in the aforementioned AD model, while simultaneously identifying potential blood biomarkers indicative of NuCerin's therapeutic action.
View Article and Find Full Text PDFPreclinical Alzheimer's prevention trials require a multi-year commitment from diverse, cognitively unimpaired individuals willing to receive biomarker results of confirmed Alzheimer's pathology and possible ApoE4 status. Participants learn new terms such as ARIA, edema and microhemorrhage and undergo numerous MRI scans for safety monitoring. They take quarterly composite Alzheimer's assessments that are anxiety-provoking and highlight weaknesses which may have been unrecognized in daily life.
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