Microbially Inspired Calcium Carbonate Precipitation Pathway Integrated Polyelectrolyte Capsules (MICPC) for Biomolecules Release.

Complexation between oppositely charged polyelectrolytes offers a facile single-step strategy for assembling functional micro-nano carriers for efficient drug and vaccine delivery. However, the stability of the delivery system within the physiological environment is compromised due to the swelling of the polyelectrolyte complex, driven by the charge shielding effect, and consequently leads to uncontrollable burst release, thereby limiting its potential applications. In a pioneering approach, cellular pathway-inspired calcium carbonate precipitation pathways are developed that are integrated into polyelectrolyte capsules (MICPC). These innovative capsules are fabricated at the interface of all-aqueous microfluidic droplets, resulting in a precisely controllable and sustained release profile in physiological conditions. Unlike single-step polyelectrolyte assembly capsules which always perform rapid burst release, the MICPC exhibits a sustainable and tunable release pattern, releasing biomolecules at an average rate of 3-10% per day. Remarkably, the degree of control over MICPC's release kinetics can be finely tuned by adjusting the quantity of synthesized calcium carbonate particles within the polyelectrolyte complex. This groundbreaking work not only deepens the insights into polyelectrolyte complexation but also significantly enhances the overall stability of these complexes, opening up new avenues for expanding the range of applications involving polyelectrolyte complex-related materials.

Bacteria-Inspired Aqueous-in-Aqueous Compartmentalization by In Situ Interfacial Biomineralization.

Compartmentalization is essential for living cells to orchestrate their biological processes with controlled external influences. Thus, compartmentalization has been a constant theme for cell-mimicking materials. Despite recent advances in engineering compartmentalized materials as synthetic cells and organelles, it remains difficult to produce robust and well-ordered compartments with secluded environments in aqueous surroundings. Nature creates hierarchically ordered compartmentalized materials by utilizing bio-catalyzed mineralization, inspired by which, mechanically robust all-aqueous compartments are developed by engineering a mild biomimetic mineralization at aqueous/aqueous interfaces. The enzyme-induced biomineralization generates a layer of densely-packed particles, acting as an armor to enclose aqueous interiors. This strategy of in situ bio-synthesized compartments is different from current strategies, where compartments are constructed by randomly adsorbed particles at interface, leading to inadequately controlled properties of compartments. To demonstrate the robustness and adaptiveness of the in situ bio-synthesized all-aqueous compartments, these are utilized as drug delivery materials by sequestering protein drugs at their aqueous interiors and releasing when exposing to gastric environments. The study provides new ways to fabricate compartmentalized materials with well-defined properties, unlocking routes to the next generation of self-assembled materials and structures by integrating aqueous two-phase systems with biomineralization.

Multishell Colloidosome Platform with Sequential Gastrointestinal Resistance for On-Demand Probiotic Delivery.

Probiotic-based oral therapy can potentially prevent and treat diseases by regulating the balance of intestinal flora. However, significant loss of viability and bioactivity of probiotics before reaching the colon results in low delivery efficiency and therapeutic effects, which limits their clinical applications. Here, this work proposes a multishell colloidosome (MSC) platform with sequential gastrointestinal resistance for on-demand probiotic delivery based on biomimetic mineralization and microfluidic technology. Notably, the viability of the decorated probiotics increases 280-fold compared to that of free bacteria during preservation. Because of the sequential gastrointestinal resistance of MSC, encapsulated probiotics exhibit high viability (61%) under continuous exposure to extreme acidity, bile salt erosion, and enzymatic action, whereas free bacteria have a viability of 0%. Moreover, in vitro and in vivo studies reveal that MSC mainly releases probiotics in the colon and improves colonic colonization by probiotics to maintain the integrity of the intestinal barrier and regulate the balance of intestinal flora. Consequently, MSC significantly improves the therapeutic effect on colitis in mice. The MSC platform provides a promising delivery strategy to enhance the efficacy of orally administered probiotics.