Synthesis and characterization of cystamine conjugated chitosan-SS-mPEG based 5-Fluorouracil loaded polymeric nanoparticles for redox responsive drug release

Trigger-responsive materials are capable of controlled drug release in the presence of a specific trigger. Reduction induced drug release is especially interesting as the reductive stress is higher inside cells than in the bloodstream, providing a conceptual controlled release mechanism after cellular uptake. In this work, we report the synthesis of 5-fluorouracil (5-FU) molecularly imprinted polymers (MIPs) based on poly(2-isopropenyl-2-oxazoline) (PiPOx) using 3,3′-dithiodipropionic acid (DTDPA) as a reduction-responsive functional cross-linker. The disulfide bond of DTDPA can be cleaved by the addition of tris(2-carboxyethyl)phosphine (TCEP), leading to a reduction-induced 5-FU release. Adsorption isotherms and kinetics for 5-FU indicate that the adsorption kinetics process for imprinted and non-imprinted adsorbents follows two different kinetic models, thus suggesting that different mechanisms are responsible for adsorption. The release kinetics revealed that the addition of TCEP significantly influenced the release of 5-FU from PiPOx-MIP, whereas for non-imprinted PiPOx, no statistically relevant differences were observed. This work provides a conceptual basis for reduction-induced 5-FU release from molecularly imprinted PiPOx, which in future work may be further developed into MIP nanoparticles for the controlled release of therapeutic agents.

Section: In Vitro Release Studiesmentioning

confidence: 95%

Reduction-Responsive Molecularly Imprinted Poly(2-isopropenyl-2-oxazoline) for Controlled Release of Anticancer Agents

Cegłowski

Jerca

et al. 2020

“…To modulate drug release in the tumour microenvironment, redox/enzyme responsive linkage can be inserted into the hydrophobic–hydrophilic conjugate structure. An example of this type of conjugate is the disulfide linkage for redox-responsive drug delivery, which is cleaved by a high intracellular glutathione concentration [65,66,67]. Specifically, in the work of Liu et al [49], cystamine was conjugated between deoxycholic acid (the hydrophobic segment) and chondroitin sulfate (the hydrophilic portion) for the delivery of docetaxel to treat melanoma.…”

Section: Modified Hydrophobic-hydrophilic Nanoconjugates For the Dmentioning

confidence: 99%

Nanoconjugation and Encapsulation Strategies for Improving Drug Delivery and Therapeutic Efficacy of Poorly Water-Soluble Drugs

Tran

2019

Nanoconjugations have been demonstrated to be a dominant strategy for drug delivery and biomedical applications. In this review, we intend to describe several strategies for drug formulation, especially to improve the bioavailability of poorly water-soluble molecules for future application in the therapy of numerous diseases. The context of current studies will give readers an overview of the conjugation strategies for fabricating nanoparticles, which have expanded from conjugated materials to the surface conjugation of nanovehicles. Moreover, nanoconjugates for theranostics are also discussed and highlighted. Overall, these state-of-the-art conjugation methods and these techniques and applications for nanoparticulate systems of poorly water-soluble drugs will inspire scientists to explore and discover more productive techniques and methodologies for drug development.

“…Cystamine is a disulfide diamine compound generated from the oxidation of two cysteamine thiols [19]. Both cystamine and cysteamine are found within the human body, thus potentially suitable for pharmaceutical purposes and as cross-linkers for redox function in drug carriers [20,21].…”

Section: Introductionmentioning

confidence: 99%

Redox-Sensitive Linear and Cross-Linked Cystamine-Based Polymers for Colon-Targeted Drug Delivery: Design, Synthesis, and Characterisation

Yusuf

Chiu

et al. 2020

Cystamine-based polymers may help to achieve controlled and targeted drug delivery to the colon due to their susceptibility to breakage of the disulfide linkage in the low redox potential environment of the colon. In this study, two linear cystamine-based polymers with similar repeating units (LP1 and LP2) and a cross-linked cystamine-based polymer (BP) were synthesised and their kinetics and the various physical conditions underlying cystamine-based polymerisation were evaluated. In brief, N1,N6-bis(2-(tritylthio)ethyl)adipamide (2) was synthesised from the reaction of triphenylmethanol and cysteamine. Next, the trityl group of 2 was removed with trifluoroacetic acid and triethylsilane before proceeding to oxidative polymerisation of the end product, N1,N6-bis(2-mercaptoethyl)adipamide (3) to LP1. The Schotten-Bauman reaction was applied to synthesise LP2 and BP from the reaction of cystamine with adipoyl chloride or trimesoyl chloride. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, and mapping showed that oxygen, nitrogen, sulfur, and carbon were homogenously distributed in the polymers, with LP2 and BP having less porous morphologies compared to LP1. Results of zinc-acetic acid reduction showed that all polymers began to reduce after 15 min. Moreover, all synthesised polymers resisted stomach and small intestine conditions and only degraded in the presence of bacteria in the colon environment. Thus, these polymers have great potential for drug delivery applications. LP2 and BP, which were synthesised using the Schotten-Bauman reaction, were more promising than LP1 for colon-targeted drug delivery.