Engineered Emulsions Stabilised by Thermoresponsive Branched Copolymers for Pharmaceutical Applications
Creators: name: Rajbanshi, Abhishek
Publisher: name: UH Research Archive
Year: 2023
Subjects: Thermoresponsive emulsion
Gels
branched copolymer surfactants

description: This research work explored thermoresponsive emulsions and investigated their potential in delivering drugs through in situ gelling pharmaceutical formulations. Employing thermoresponsive branched copolymer surfactants (BCSs), this study established their efficacy in creating stable emulsions with reversible gelation triggered by changes in temperature. While previous research had shown BCSs' capacity to transition emulsions to gels via pH alteration, this study innovatively proposed the concept of thermoresponsive emulsions that respond at physiological temperatures. The focus was on generating materials capable of shifting from a liquid to a gel state upon warming, promising enhanced healthcare technologies like in situ gel-forming materials for diverse drug delivery routes. The thermoresponsive BCSs used to stabilise the emulsions that showed sol-gel transition upon heating were synthesised with a lower critical solution temperature (LCST) monomer, a hydrophilic macromonomer, a crosslinker and a hydrophobic chain transfer agent. All these components were proven to contribute to the gelation behaviour. The research investigated the interplay between temperature and BCS structure at both macro and nanoscales, dissecting how these engineered emulsions react to temperature shifts. Moreover, the emulsions held the potential for solubilisation of various drug chemistries and explored their drug delivery activities via in situ gelation. This thesis evaluated the rheology of the engineered emulsions based on polymer architecture, branching, molecular weight, and hydrophobic end groups, influencing gel formation on heating. Furthermore, poly(ethylene glycol) methyl ether methacrylate’s role in controlling emulsion responsiveness was highlighted, with longer poly(ethylene glycol) chains inducing thermogelation and shorter chains causing emulsion breakdown upon mild heating. The ratio of LCST monomer to hydrophilic macromonomer tightly governed gelation temperature. Expanding these findings, the research explored various pharmaceutically relevant oils in the emulsion system, along with additives to enhance stability. The addition of methylcellulose significantly improved stability, and small-angle neutron scattering (SANS) helped to understand the gelation mechanism and the nanoscale processes within BCS-stabilised emulsions. Furthermore, these emulsion systems were investigated as pharmaceutical formulations, analysing drug release mechanisms and compatibility with nasal spray devices. These advanced emulsions showed promise in controlled drug release and nasal spray device compatibility. In summary, this thesis showed a new frontier in drug delivery through temperatureresponsive emulsions, offering smart dosage forms with transformative potential. The work not only advances understanding in thermoresponsive engineered emulsions but also lays the groundwork for personalised medicine and targeted drug delivery, promising improved patient outcomes and reduced dosing frequency.