[3S03m] 08. Functional Molecules and Materials for Biological Systems - Part 1

10:00 AM - 10:40 AM JST(1:00 AM - 1:40 AM UTC)

[3FMBS-02-KL] Tiny Bubbles, Big Impact: Microfluidic Strategies for Precision Drug Delivery

○Stephen Evans¹ (1. University of Leeds (UK))

Keywords:

Therapeutic delivery,microfluidics,on chip models,microbubbles,ultrasound

Microfluidically engineered micro and nanobubbles are emerging as powerful theranostic agents that combine high resolution ultrasound imaging with targeted low toxicity drug delivery This talk presents advances in the generation characterisation and therapeutic application of diagnostic and drug loaded microbubbles DLMB ThMB produced using precision microfluidic platforms Our systems generate monodisperse lipid coated microbubbles 15 to 25 um at approximately 10e8 MB per mL and Microspray derived populations at 10e9 MB per mL with tight control between 05 and 35 um Solutions can be saturated with chosen gases or fluorocarbon liquids while surface tension is reduced through fluorinated lipids and surfactants and shell stiffness tuned with long chain lipids These features support stable acoustically responsive bubbles with predictable in vitro and in vivo lifetimes Nanobubble formulations reach 10e11 to 10e12 particles per mL typically forming buoyant echogenic mixtures of nanobubbles liposomes and fluorocarbon droplets Distinct phase change behaviour particularly in C4F10 nanobubbles suggests reversible gas liquid transitions that may underpin their long stability and potential for triggered drug release A major focus is DLMBs produced on chip at 10e9 MB per mL for highly localised ultrasound triggered drug deposition In multiple cancer models DLMB plus ultrasound suppresses tumour growth or achieves complete elimination while using dramatically reduced drug concentrations With SN38 DLMBs require around 20 fold less drug than systemic delivery to achieve the same therapeutic effect widening the therapeutic window and eliminating systemic toxicity DLMBs can also be freeze dried and stored for over six months enabling long term stability Incorporating liposomes into the microbubble shell significantly extends intravascular drug circulation compared with free liposomes enhancing exposure and delivery efficiency Therapeutic mechanisms are investigated using advanced in vitro systems including 3D pancreatic and colorectal cancer spheroids vascular on chip models and 2D monolayers These platforms provide mechanistic insight into transport dynamics acoustic behaviour and sonoporation mediated uptake under physiologically relevant conditions Beyond oncology DLMBs and peptide loaded microbubbles demonstrate potent efficacy against Staphylococcus aureus biofilms highlighting their potential for treating persistent bacterial communities Overall this work shows how microfluidic control of bubble size shell chemistry fluorocarbon loading and acoustic responsiveness enables a new generation of high precision low toxicity theranostic agents Integrating microbubble engineering with ultrasound physics and disease relevant 3D and preclinical models outlines a translational pathway for targeted therapy across cancer infectious disease and beyond