SoftNanoHybrid · Polymer-Nanoparticle co-assembly for drug targeting and release kinetics: Investigation on Structure, Morphology, Responsiveness, and Nanoparticle distribution

Polymer-Nanoparticle co-assembly for drug targeting and release kinetics: Investigation on Structure, Morphology, Responsiveness, and Nanoparticle distribution

The soft nanohybrids formed by the bacterial amphiphiles in water are characterised with an aim to understand their role in various bacteriological processes e.g. bioadhesion, colonisation and antimicrobial resistance. A biopolymer (lipoteichoic acid, LTA) that is pH responsive has been used as a central building unit for the model systems for self-assembly. We have successfully formed and characterised the LTA self assemblies in water and examined their adsorption at the interfaces. In the actual bacteria membrane, the LTA is adhered directly via lipid-like chains with the phospholipid membrane, and accordingly could play a major role in the structural stability and integrity of the membrane. These possibilities were checked by designing mixed vesicles from phospholipids representing the actual composition of the bacteria membrane and LTA. These structures were analysed by SANS, DLS and CryoTEM, which provided conclusions on the structural effects caused by LTA on the size and distribution of the mixed vesicles. According to National Health Services (NHS) UK, several strains of bacteria have reportedly developed resistance to many different types of antibiotics, including: MRSA (methicillin-resistant Staphylococcus aureus), Clostridium difficile and the bacteria that cause multi-drug-resistant tuberculosis. In order to encounter this challenge, the molecular interactions within bacteria membrane must be understood by detailed experimental approaches, which would presumably provide suggestions for the design and development of the antibiotics with specific structural properties to tackle the resistance caused by the bacteria. Our experiments have provided useful results in this direction and this field remains open with several unanswered questions about the physicochemical understanding of these bacteria membrane processes. The objective of the project was to understand self-assembly behaviour of soft nanohybrids. Having examined the availability and costs of a number of block copolymers with different molecular weight distribution, we have focused on mixed liposomes/vesicles and their structural transformations on interactions with lipoteichoic acid (LTA).

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