Multicellular Lipid Compartments for Scalable Micro-Compartmentalization with Environmentally Responsive Release.

Smart drug release systems have gained attention as a method of using existing medicines in a more effective manner. However, topically applied medicines still rely on uncontrolled diffusion for delivery. Here we propose the use of multicellular lipid compartments (MCLCs) to encapsulate, regulate and control the release of encapsulated drugs. MCLC systems are lipid-based, semi-solid, high internal phase emulsions (HIPEs) with an aqueous dispersed phase pressed into tightly bound micro-compartments with a multicellular-like morphology. The resulting micro-compartments are typically between 20-200 µm and delineated by a continuous lipid-hybrid membrane. The lipid membranes show high stability over months of observations and have semi-permeable properties, allowing water and other small molecules across while retaining larger target molecules. MCLC systems are easily formed on milliliter scales within seconds from desired aqueous solutions by simple application of “lipid-inks”. These lipid-inks are formed from a mixture of natural phospholipids, commercial surfactants, and oils. We show that phospholipids play a crucial role in driving the distinctive cellular morphologies while the surfactants help increase the stability of the system. <br/>To create properties for real-world applications, we encapsulate MCLC systems within polysaccharide hydrogels to improve their stability and enable their use as practical, tangible devices. Using these MCLC-hydrogels we demonstrate the release of the encapsulated contents into external aqueous environments using membrane solubilization strategies. Release rates from the membrane are shown to be related to compartmentalization conditions due to sequential membrane breakdown. Additionally, we show membrane breakdown can be triggered and enhanced by introducing ionic species, leading to environmentally sensitive release conditions. The compartmentalization strategy also allowed for heterogenous cellular mixing, creating single MCLC systems consisting of multiple different types of separated drugs, and multiple release conditions leading to multi-step or sustained delivery outputs. We believe this work could lead to medical patches for smart and customizable trans-dermal drug delivery. Their environmental sensitivity could lead to smart-release capabilities capable of modulating drug release depending on skin conditions, further increasing their effectiveness by introducing conditional delivery. <br/>Beyond drug delivery, we also hope to develop MCLC systems into simple cell models, communicating permeable networks and bio-inspired soft-robots.