Unravelling the interactions between small molecules and liposomal bilayers via molecular dynamics and thermodynamic modelling.

Lipid-based drug delivery systems hold immense promise in addressing critical medical needs, from cancer and neurodegenerative diseases to infectious diseases. By encapsulating active pharmaceutical ingredients - ranging from small molecule drugs to proteins and nucleic acids - these nanocarriers enhance treatment efficacy and safety. However, their commercial success faces hurdles, such as the lack of a systematic design approach and the issues related to scalability and reproducibility. This work aims to provide insights into the drug-phospholipid interaction by combining molecular dynamic simulations and thermodynamic modelling techniques. In particular, we have made a connection between the structural properties of the drug-phospholipid system and the physicochemical performance of the drug-loaded liposomal nanoformulations. We have considered two prototypical drugs, felodipine (FEL) and naproxen (NPX), and one model hydrogenated soy phosphatidylcholine (HSPC) bilayer membrane. Molecular dynamic simulations revealed which regions within the phospholipid bilayers are most and least favoured by the drug molecules. NPX tends to reside at the water-phospholipid interface and is characterized by a lower free energy barrier for bilayer membrane permeation. Meanwhile, FEL prefers to sit within the hydrophobic tails of the phospholipids and is characterized by a higher free energy barrier for membrane permeation. Flory-Huggins thermodynamic modelling, small angle X-ray scattering, dynamic light scattering, TEM, and drug release studies of these liposomal nanoformulations confirmed this drug-phospholipid structural difference. The naproxen-phospholipid system has a lower free energy barrier for permeation, higher drug miscibility with the bilayer, larger liposomal nanoparticle size, and faster drug release in the aqueous medium than felodipine. We suggest that this combination of molecular dynamics and thermodynamics approach may offer a new tool for designing and developing lipid-based nanocarriers for unmet medical applications.

Plastic surgery procedure unit: A streamlined care model for minor and intermediate procedures: A cost-benefit analysis.

INTRODUCTION: The advent of wide-awake local anaesthesia has led to a reduced need for main theatre for trauma and elective plastic procedures. This results in significant cost-benefits for the institution. This study aims to show how a dedicated 7 days/ week plastic surgery procedural (PSP) unit, performing both elective and trauma surgeries, can lead to significant cost-benefits for the institution. METHODS: Retrospective review of all cases performed in the PSP unit between 1 September and 31 August 2018. We utilised hospital directory admissions data and the hospital's intranet operating theatre system to calculate hospital days saved. Cost analysis was performed using Saolta financial data. RESULTS: A total of 3058 operations were performed. Of these operations, 2388 cases were elective and 670 were trauma cases. The average waiting time for trauma cases for main operating theatre was 1.4 days, saving a total of 487 hospital days. The total savings associated with hospital bed days were €347,861. The estimated resource savings from performing a procedure in PSP compared with main theatre with regional anaesthesia were €529.00 and €391.00 without regional anaesthesia. The cost saved due to resources was therefore €337,226. The total cost-benefit associated with performing surgeries in PSP including hospital days and resources saved was calculated as €685,087. CONCLUSION: This study shows the benefit of performing elective and trauma operations in minor procedure units such as PSP. PSP results in a more efficient service, reducing waiting times for surgery, shorter hospital stay, reduced operating cost and an overall significant cost saving.