Zwitterionic Nanocapsules with Salt- and Thermo-Responsiveness for Controlled Encapsulation and Release

Abstract

Intelligent polymer nanocapsules that can not only encapsulate substances efficiently but also release them in a controllable manner hold great potential in many applications. To date, although intensive efforts have been made to develop intelligent polymer nanocapsules, how to construct the well-defined core/shell structure with high stability via a straightforward method remains a considerable challenge. In this work, the target novel zwitterionic nanocapsules (ZN C s) with a stable hollow structure were synthesized by inverse reversible addition fragmentation transfer (RAFT) miniemulsion interfacial polymerization. The shell gradually grew from the water/oil interface due to the interfacial polymerization, accompanied by the cross-linking of the polyzwitterionic networks, where the core/shell structure could be well-tuned by adjusting the precursor compositions. The resultant ZN C s exhibited a salt-/thermoinduced swelling behavior through the phase transition of the external zwitterionic polymers. To further investigate the functions of ZN C s, different substances, such as methyl orange and bovine serum albumin (BSA), were encapsulated into the ZN C s with a high encapsulation efficiency of 89.3 and 93.6%, respectively. Interestingly, the loaded substances can be controllably released in aqueous solution triggered by salt or temperature variations, and such responsiveness also can be utilized to bounce off the bacteria adhered on target surfaces. We believe that these designed salt-and thermo-responsive intelligent polymer nanocapsules with well-defined core/shell structures and antifouling surfaces should be a promising platform for biomedical and saline related applications.

Zwitterionic Biomaterials

“…A triple-network hydrogel with two PSB networks demonstrated a high compression fracture stress of around 18.2 MPa, which can even be maintained in salt solutions such as PBS and seawater (Figure c,d) . The salt-responsiveness and thermoresponsiveness of PSB could also be utilized to design environmental stimuli-responsive materials, such as hydrogels, microgels, and nanogels for controlled drug release.…”

Zwitterionic nanocapsule-based wound dressing with the function of gradient release of multi-drugs for efficient wound healing

“…ZNs were synthesized by inverse RAFT miniemulsion interfacial polymerization according to our previous report. 42 To form a continuous oil phase, the amphi-RAFT agent (6 wt% in toluene, 0.96 g), Tween 80 (0.02 g), Span 80 (0.06 g) and toluene (20 mL) were added by sequence into the flask and the mixture was stirred for 30 min. In another flask, DVBAPS (0.975 g, 3.45 mmol), SBMA (0.325 g, 1.11 mmol), and APS (0.023 g, 0.1 mmol) were dissolved in deionized water (1.3 mL) as a dispersed aqueous phase, followed by stirring at room temperature for 30 min.…”

“…On one hand, the synthesis method does not require the use of harsh acid or alkali to remove the sacrificial template; on the other hand, the robust benzene group imparts rigidity of the polymeric shell, and a chemical cross-linker is easily introduced by this method to compensate the weak physical interactions of ZNs as well as improve the mechanical stability. 42 However, polyDVBAPS ZNs show obvious salt-triggered swelling behavior in a salt environment (swelling 2-5 times in 0.5 M saline) and the transition temperature range (45-50 1C) is far beyond the normal temperature of the human body, making polyDVBAPS ZNs unsuitable and unstable in physiological environments (salt containing environment and 37 1C). 42,43 Besides, constructing wound dressings with ZNs alone is still difficult for gradient release of two different drugs.…”

“…42 However, polyDVBAPS ZNs show obvious salt-triggered swelling behavior in a salt environment (swelling 2-5 times in 0.5 M saline) and the transition temperature range (45-50 1C) is far beyond the normal temperature of the human body, making polyDVBAPS ZNs unsuitable and unstable in physiological environments (salt containing environment and 37 1C). 42,43 Besides, constructing wound dressings with ZNs alone is still difficult for gradient release of two different drugs. As a result, a second carrier to load the 2nd drug as well as to load the 1st drug-containing ZNs is required.…”

Robust Construction of Supersmall Zwitterionic Micelles Based on Hyperbranched Polycarbonates Mediates High Tumor Accumulation

“…Polyzwitterions, as representatives of zwitterionic polymers, were facilely fabricated by reversible addition–fragmentation chain transfer (RAFT) polymerization or atom-transfer radical polymerization (ATRP) using zwitterionic (meth)­acrylate monomers. − However, these polymers with polyacrylate backbones do not possess biodegradability, which may result in bioaccumulation-related toxicity, hampering long-term applications. , Zwitterionic polypeptides possessing natural structures could be enzymatically digestible and metabolizable, exhibiting good biocompatibility and nontoxicity. , Nevertheless, synthesizing zwitterionic polypeptides requires precise control of the alternating sequence of amino acid units with opposite charges with the cumbersome process of protection and deprotection of free carboxyl and amino groups. − Therefore, flexible and concise synthetic biodegradable zwitterionic polymers are of high interest. ,− For example, Hedrick et al constructed a fully biodegradable linear zwitterionic polycarbonate based on postpolymerization functionalization of a versatile polycarbonate precursor containing substitutable pentafluorophenyl esters …”