Osmotic Delivery and Release of Lipid-Encapsulated Molecules via Sequential Solution Exchange

Passive targeted drug delivery to solid tumors is driven by the permeation of drug carriers through porous vasculature. Due to a dominant transport mechanism for the entry and migration of the drug carriers being diffusion, the passive drug delivery is relatively slow and ineffective in delivering large carriers to the desired location. Here, we propose a method for delivering liposomes into the interstitium at orders of magnitude faster than the diffusion. Using microfluidic model tumor microenvironment, we show that by exchanging the solutes of the interstitial fluid, the liposomes can respond to the change in the chemistry of the surrounding fluid, thereby penetrating deep into the confined pore space at an accelerated transport rate. In addition, by further exchanging the environment with a hypotonic solution, the delivered liposomes can expel their inner content continuously via periodic osmotic bursting, allowing controlled release of encapsulated molecules in hard-to-reach spaces. Our study suggests an active delivery strategy to enhance the permeation of therapeutic molecules into the interstitium.