Controllable Multicompartmental Capsules with Distinct Cores and Shells for Synergistic Release

Abstract

A facile and flexible approach is developed for controllable fabrication of novel multiple-compartmental calcium alginate capsules from all-aqueous droplet templates with combined coextrusion minifluidic devices for isolated coencapsulation and synergistic release of diverse incompatible components. The multicompartmental capsules exhibit distinct compartments, each of which is covered by a distinct part of a heterogeneous shell. The volume and number of multiple compartments can be well-controlled by adjusting flow rates and device numbers for isolated and optimized encapsulation of different components, while the composition of different part of the heterogeneous shell can be individually tailored by changing the composition of droplet template for flexibly tuning the release behavior of each component. Two combined devices are first used to fabricate dual-compartmental capsules and then scaled up to fabricate more complex triple-compartmental capsules for coencapsulation. The synergistic release properties are demonstrated by using dual-compartmental capsules, which contain one-half shell with a constant release rate and the other half shell with a temperature-dependent release rate. Such a heterogeneous shell provides more flexibilities for synergistic release with controllable release sequence and release rates to achieve advanced and optimized synergistic efficacy. The multicompartmental capsules show high potential for applications such as drug codelivery, confined reactions, enzyme immobilizations, and cell cultures.

Microfluidic fabrication of microparticles for biomedical applications

“…12b). 148 Each compartment is covered with a distinctive shell, allowing incorporation of multiple components and independent control over their release. In dual compartmental capsules with thermoresponsive nanogels introduced into one-half of the Janus shell, the release of actives in the two compartments can be triggered by temperature and concentration gradient, respectively.…”

“…b) Optical micrograph of microcapsules with dual compartments and heterogeneous shell, and illustration of microcapsules exhibiting both temperature triggered release and sustained release. 148 Reprinted with permission from ref. 148.…”

Heterogeneous multi-compartmental hydrogel particles as synthetic cells for incompatible tandem reactions

“…In this regard, hydrogels based systems appear promising for the construction of multi-compartmental systems. Several methods have been developed to fabricate structured hydrogels with multiple compartments 20 – 22 to load different drugs in separate compartments with a programmed, controllable sequential release. However, most such studies focused on controlling drug release from hydrogels, requiring a drug-reloading process for long-term drug delivery.…”

Functional aqueous droplet networks

“…Rupture could be induced by the addition of a chelator to sequester the divalent cations. Co-extrusion allowed the formation of multi-compartment capsules with two or three distinct compartments 180 ( Figure 33E-G). Microfluidically generated hydrogel capsules have been used to encapsulate droplet networks 56 (see Section 2.5).…”