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Monitoring the Release Mechanism of Model Drugs from Loaded Lipid Nanoparticles interacting with Lipid Membranes

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This proposal continues our previous studies (Experiments 2220789 and 2410695) on the interaction of lyotropic liquid crystalline nanoparticles (LCNPs) with supported lipid bilayers (SLBs) mimicking cellular membranes. LCNPs such as cubosomes and hexosomes are highly efficient and biocompatible nanocarriers capable of encapsulating and releasing therapeutic molecules in a controlled manner. Our earlier neutron reflectometry (NR) experiments demonstrated that the internal structure and surface charge of LCNPs strongly affect their interaction with membranes: DOPE hexosomes fused with SLBs, while GMO cubosomes accumulated and disrupted them. Further work on pH-sensitive GMO/OA systems showed structural transitions at low pH, consistent with fusion and reorganisation at the interface. In this proposal, we aim to investigate the release of the antimicrobial peptide G3 from neutral and pH-responsive LCNPs and its interaction with SLBs of varying cholesterol content using NR. By correlating the structural response of the bilayer with pH-induced phase transitions and peptide release, this study will provide nanoscale insight into the mechanisms governing drug release and membrane disruption, guiding the design of responsive LCNP carriers for biomedical applications.

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