Sequential drug release via chemical diffusion and physical barriers enabled by hollow multishelled structures

Nailiang Yang,Yang Yang,Decai Zhao,Suojiang Zhang,Dan Wang,Hongyan He,Yanlei Wang,Quan Jin,Bing Han,Yan Wei

doi:10.1038/s41467-020-18177-2

Abstract

Hollow multishelled structures (HoMSs), with relatively isolated cavities and hierarchal pores in the shells, are structurally similar to cells. Functionally inspired by the different transmission forms in living cells, we studied the mass transport process in HoMSs in detail. In the present work, after introducing the antibacterial agent methylisothiazolinone (MIT) as model molecules into HoMSs, we discover three sequential release stages, i.e., burst release, sustained release and stimulus-responsive release, in one system. The triple-shelled structure can provide a long sterility period in a bacteria-rich environment that is nearly 8 times longer than that of the pure antimicrobial agent under the same conditions. More importantly, the HoMS system provides a smart responsive release mechanism that can be triggered by environmental changes. All these advantages could be attributed to chemical diffusion- and physical barrier-driven temporally-spatially ordered drug release, providing a route for the design of intelligent nanomaterials.

Highlights

Hollow multishelled structures (HoMSs), with relatively isolated cavities and hierarchal pores in the shells, are structurally similar to cells
TiO2–HoMS samples with different shell numbers were fabricated through STA20,23 by Responsive release Sustained release adjusting the adsorption conditions of metal ions, and MIT was loaded by a typical drug-loading process[24]
X-ray diffraction confirms that TiO2–HoMS is a composite of the anatase phase (JCPDS card No 21-1272) and rutile phase (JCPDS card No 211276) (Supplementary Fig. 2e)[25]

Summary

Introduction

Hollow multishelled structures (HoMSs), with relatively isolated cavities and hierarchal pores in the shells, are structurally similar to cells. In addition to the common passive transmission through cell membranes caused by a concentration gradient, stimulus transmission is another typical property of cells allowing them adapt to the changing environment[7] In this case, it is desired to design an artificial cell that can realize sequential mass release, including both passive and stimulus transmission. Our recent perspective has revealed that HoMSs have unique mass transport properties that strictly follow a temporal and spatial order during mass diffusion through the shells[20]. In this case, it can be predicted that using HoMS as a drug carrier for antibacterial agents will show some unexpected advantages. Because MIT molecules can form hydrogen bonds with TiO2 and π–π stacking with each other[22], and due to the capillary force in HoMS, notably, the sequential release, i.e., burst release, sustained release, and stimulus-responsive release, is realized in a single HoMS particle (Fig. 1), which is named as temporally, spatially ordered drug release

Methods

Results

Conclusion