H2O2-Responsive Nanoparticle Based on the Supramolecular Self-Assemble of Cyclodextrin

Abstract

Designing stimuli responsive, controllable and biocompatible multifunctional nanoparticles is an important progress in the current quest for drug delivery systems. Herein, we devoted to developing a β-cyclodextrin (β-CD) based drug delivery nanoparticles (NPs) that release Bovine serum albumin (BSA) via glucose-responsive gate. The design involves synthesis of sodium alginate with β-CD modified (Alg-β-CD) and methoxypolyethylene glycol (mPEG-Fc) containing ferrocene (Fc) uncharged end-capping. When α-cyclodextrin (α-CD) was added with these two segments, the stable non-covalent supramolecular structure of Alg-β-CD/mPEG-Fc/α-CD can be self-assembled into NPs in aqueous solution. BSA loaded Alg-β-CD/mPEG-Fc/α-CD also has been prepared. Interestingly, these supramolecular Alg-β-CD/mPEG-Fc/α-CD/BSA NPs showed uniform sphere structure and constant BSA loading content. Also, this new kind of NPs can disassemble in the present of hydrogen peroxide (H2O2). Since glucose oxidase (GOD) can oxidize glucose and produce H2O2, so this kind of polymeric NPs can also have glucose responsive behavior in the GOD containing environment. Developed functional Alg-β-CD/mPEG-Fc/α-CD might be a promising drug delivery strategy for diabetes or immunotherapy with more efficiency.

Biocompatible Polymers Combined with Cyclodextrins: Fascinating Materials for Drug Delivery Applications

“…After oxidation of Fc, NPs became unstable as a result of cleavage of the IC between β-CD and further BSA may be released in a controlled manner. Moreover, the presence of β-CD in the NPs structure enhance the encapsulation efficiency [184]. Also, the well-known interaction between β-CD and adamantane [185] was used to prepared self-assembled NPs from two series of dextran polymers a) dextran modified by β-CD and b) dextran modified by adamantyl groups.…”

Cyclodextrins in drug delivery: applications in gene and combination therapy

“…Polyrotaxanes are often cationic polymers themselves, but have additional characteristics which make them unique. A linear polymer backbone, such as PEG, interacts with CDs such that they thread along the PEG axis, forming a supramolecular structure [81,82]. In a polypseudorotaxane, CDs can freely slide along and off the linear backbone.…”

“…Ferrocene (Fc) has also been used in host/guest fashion. With a strong initial association, (log K=3.68) [25] oxidation of Fc leads to dissociation of the complex, creating a redox-responsive system for delivery [82]. Regardless of the molecules used to form the CD complex, all these modifications impart additional properties to existing gene delivery systems.…”

“…The usage of CD is advantageous in these cases due to its ability to fulfill multiple functions: hosting small molecule drugs, acting as a linker or modular component, reducing immunogenicity, and disrupting membranes. CD forms inclusion complexes with many different drug types, including chemotherapeutics [59,104,[128][129][130], immunomodulators [105,118,131], cytokines [132], and even proteins [82,133]. When the modularity of CD hydroxyl groups is used to create gene delivery systems, the CD pocket often goes unused, and could be easily loaded with a small-molecule drug to integrate a secondary therapy type such as chemo-or immunotherapy.…”

Oxidant-responsive ferrocene-based cyclodextrin complex coacervate core micelles

“…By introducing host-guest interactions in C3Ms, the stability against salt and competing cyclodextrin could be adjusted by finely tuning the charge of the adamantane guest (15). Here, we selected ferrocene as guest for its well-known 1:1 inclusion complex with β-CD, with an association constant (k a ) around 4.1 10 3 M −1 (in its reduced form) (21)(22)(23)(24)(25)(26) and for its responsivity towards mild oxidants, such as FeCl 3 , AgNO 3 , I 2 (27)(28)(29) or H 2 O 2 (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). The oxidation reaction of ferrocene to ferrocenium (Fc + ) causes consequently the dissociation of the Fc + from the β-CD (k a 15 M −1 ).…”