Stimulus-responsive delivery systems hold great promise in cancer treatment. Recently, dual redox-responsive liposomes have garnered significant attention as a novel stimulus-responsive delivery method. CD Formulation is dedicated to leveraging state-of-the-art technologies and specialized expertise to create high-performance liposomes that respond to dual redox conditions, providing advanced solutions for precise and effective drug delivery.
Redox signaling plays an important role in many aspects of physiology, including the cardiovascular system. Disorder of redox regulation is associated with many pathological conditions. Redox signaling involves the production of a particular redox species in a specific place at a specific time. In the tumor microenvironment, cancer cells have higher levels of glutathione (about 2-20 mM) due to specific environmental and nutritional requirements as well as genetic changes. When administered, nanocarriers can accumulate in tumor tissues over long cycles by enhancing permeability and retention (EPR) and be absorbed by tumor cells through endocytosis. Subsequently, at high redox potential, the redox reaction chain is destroyed, resulting in structural decomposition of the nanocarriers leading to rapid drug release. In healthy tissues with low redox potential, the nanocarrier structure remains intact by exploiting the reduction potential gradient between cancer cells and healthy cells, minimizing side effects. Dual redox-responsive liposomes represent an innovative multi-reactive liposome system.
Fig.1 Schematic representation of DOX release under the conditions of GSH and H2O2. (Yadav S, et al., 2023)
Redox systems are crucial for maintaining cell homeostasis. In physiological conditions, cells maintain oxidation-reduction balance by generating and eliminating reactive oxygen/nitrogen species (ROS/RNS). We help our clients build suitable trigger strategies by studying ROS systems (such as free radicals like superoxide (O2−) and hydroxyl radical (HO·), as well as non-free radicals like hydrogen peroxide (H2O2)) and RNS systems (including nitric oxide (NO·), peroxynitrite (ONOO−)), GSH system, thioredoxin (Trx) system, glutaredoxin (Grx) system, and peroxidases (Prxs).
Crosslinkers play a crucial role in the development of stimulation-responsive vectors, and disulfide/diselenide bonds are a good candidate for crosslinkers because of their low bond dissociation energy and susceptibility to oxidation even under weak stimuli. To help customize dual oxidation-reduction liposomes that meet specific requirements, we use screening and a combination of linkers.
The service focuses on studying the Redox response behavior of liposomes by observing their morphology and size changes in different Redox environments. We will first simulate the conditions surrounding the tumor cells (GSH and H2O2 environment) and then observe the structural changes during lipid incubation with GSH and H2O2.
We provide physical and chemical characterization of liposomes such as particle size, charge distribution, charge load and encapsulation rate, viscosity, rheology, appearance, stability, etc. In vitro characterization services include cell uptake rate assay, cytotoxicity assay, and in vitro release assay. In vivo characterization services such as in vivo distribution analysis, in vivo bioactivity analysis, in vivo stability analysis, etc.
Techniques and Platforms | Specifics |
Redox trigger strategies study platform |
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Synthesis techniques of crosslinking agents |
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Characterization Platform |
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Technology: PD-L1 inhibitor conjugate polymer-liposomes technique
Journal: ACS Applied Materials & Interfaces
IF: 9.5
Published: 2017
Results: By the non-covalent supramolecular inclusion body interaction between ferrocene (CPT) and β-cyclodextrin (β-CD) modified by camptothecin at the end of methoxy polyethylene glycol (mPEG), a double REDOX and biolever-triggered supramolecular system was established. Using these two fragments, it is possible to form a stable non-covalent supramolecular structure, namely mPEG-β-CD/Fc-CPT, which then self-assembles into a micellar structure in water. Interestingly, these supramolecular micelles exhibited uniform globular structure, high and constant drug loading, ultrafast REDOX reactive drug release, and showed the same cell proliferation inhibition against A549 cancer cells. Cytotoxicity evaluation of mPEG-β-CD also showed good biocompatibility. It is expected that this supramolecular complex may become an alternative to a new promising drug delivery system.
Fig.2 Release profiles of CPT from the mPEG-β-CD/Fc-CPT supramolecular complex micelles. (Yang Kang, et al., 2017)
With state-of-the-art technology and platforms, CD Formulation strives to deliver the most intelligent dual redox-responsive liposomes. If you require any assistance, please do not hesitate to contact us.
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