Polylactic acid nano- and microchamber arrays for encapsulation of small hydrophilic molecules featuring drug release via high intensity focused ultrasound

Abstract

Long term encapsulation combined with spatiotemporal release for a precisely defined quantity of small hydrophilic molecules on demand remains a challenge in various fields ranging from medical drug delivery, controlled release of catalysts to industrial anti-corrosion systems. Free-standing individually sealed polylactic acid (PLA) nano- and microchamber arrays were produced by one-step dip-coating a PDMS stamp into PLA solution for 5 s followed by drying under ambient conditions. The wall thickness of these hydrophobic nano-microchambers is tunable from 150 nm to 7 μm by varying the PLA solution concentration. Furthermore, small hydrophilic molecules were successfully in situ precipitated within individual microchambers in the course of solvent evaporation after sonicating the PLA@PDMS stamp to remove air-bubbles and to load the active substance containing solvent. The cargo capacity of single chambers was determined to be in the range of several picograms, while it amounts to several micrograms per cm. Two different methods for sealing chambers were compared: microcontact printing versus dip-coating whereby microcontact printing onto a flat PLA sheet allows for entrapment of micro-air-bubbles enabling microchambers with both ultrasound responsiveness and reduced permeability. Cargo release triggered by external high intensity focused ultrasound (HIFU) stimuli is demonstrated by experiment and compared with numerical simulations.

Stimuli-Responsive Drug Release from Smart Polymers

“…Micelles were tailored by controlling the ratio of hydrophilic and hydrophobic block copolymers and exhibited a significant release of dexamethasone. Gai et al developed free-standing biocompatible polylactic acid (PLA) nano- and micro-chamber arrays using two different methods for encapsulation, one-step dip-coating and microcontact printing of air, NaCl, and rhodamine B dye [26]. This work showed that the formation of microchambers can provide long-term encapsulation of small hydrophilic molecules and the release profiles of the microchambers with and without the use of HIFU [26].…”

“…Gai et al developed free-standing biocompatible polylactic acid (PLA) nano- and micro-chamber arrays using two different methods for encapsulation, one-step dip-coating and microcontact printing of air, NaCl, and rhodamine B dye [26]. This work showed that the formation of microchambers can provide long-term encapsulation of small hydrophilic molecules and the release profiles of the microchambers with and without the use of HIFU [26]. With the use of HIFU treatment, the microchambers release around four times the amount of the group without the HIFU treatment [26].…”

Colloids, nanoparticles, and materials for imaging, delivery, ablation, and theranostics by focused ultrasound (FUS)

“…Gai et al, also used trapped air inside the microwells for the on-demand release of encapsulated drugs 230. They first prepared microwells on PDMS membranes and loaded the wells with a model compound; Rhodamine B.…”

Polyelectrolyte–Graphene Oxide Multilayer Composites for Array of Microchambers which are Mechanically Robust and Responsive to NIR Light

“…Enhanced mechanical properties of PEGOM films could be specifically advantageous for making 3D structures, e.g., an array of microchambers developed recently . Potential applications of these structures include micropackaging of drugs, or sensors for rapid diagnostics of biological fluids, where resilience of the microchambers toward external stresses is required to avoid accidental burst release, the event that could be catastrophic. Moreover, GO could be used to provide near infrared (NIR) light responsiveness, which is important for many release‐on‐demand applications in biological systems as NIR light penetrates into the biological tissues for up to 10 cm causing no harm …”