Quantitative Visualization of Lipid Nanoparticle Fusion as a Function of Formulation and Process Parameters.

Lipid nanoparticles (LNPs) have proven to be promising delivery vehicles for RNA-based vaccines and therapeutics, particularly in LNP formulations containing ionizable cationic lipids that undergo protonation/deprotonation in response to buffer pH changes. These nanoparticles are typically formulated using a rapid mixing technique at low pH, followed by a return to physiological pH that triggers LNP-LNP fusion. A detailed understanding of these dynamic processes is crucial to optimize the overall performance and efficiency of LNPs. However, knowledge gaps persist regarding how particle formation mechanisms impact drug loading and delivery functions. In this work, we employ single-molecule Convex Lens-induced Confinement (CLiC) microscopy in combination with Förster resonance energy transfer (FRET) measurements to study LNP fusion dynamics in relation to various formulation parameters, including lipid concentration, buffer conditions, drug loading ratio, PEG-lipid concentrations, and ionizable lipid selection. Our results reveal a strong correlation between the measured fusion dynamics and the formulation parameters used; these findings are consistent with DLS and Cryo-TEM-based assays. These measurements offer a cost-effective method for characterizing and screening potential drug candidates and can provide additional insights into their design, with opportunities for optimization.

Key Components for the Delivery of Palliative and End-of-Life Care in Care Homes in Hong Kong: A Modified Delphi Study.

Integrating the palliative care approach into care home service to address the complex care needs of older adults with frailty or advanced diseases has been increasingly recognized. However, such a service is underdeveloped in Hong Kong owing to socio-cultural and legal concerns. We adopted a modified Delphi study design to identify the key components for the delivery of palliative and end-of-life care in care home settings for the local context. It was an iterative staged method to assimilate views of experts in aged care, palliative care, and care home management. A multidisciplinary expert panel of 18 members consented to participate in the study. They rated their level of agreement with 61 candidate statements identified through a scoping review in two rounds of anonymous surveys. The steering group revised the statements in light of the survey findings. Eventually, the finalized list included 28 key statements concerning structure and process of care in seven domains, namely policy and infrastructure, education, assessment, symptom management, communication, care for dying patients, and family support. The findings of this study underscored concerns regarding the feasibility of statements devised at different levels of palliative care development. This list would be instrumental for regions where the development of palliative and end-of-life care services in care home setting is at an initial stage.