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Custom pH-redox Responsive Liposome Service

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Stimulus-responsive nanomedicine delivery systems can modulate the release of the payload in a precise manner based on internal microenvironment conditions (such as temperature, pH, oxidation-reduction, and enzymes) to achieve potent anti-cancer effects with reduced side effects. Among these, pH/oxidation-reduction dual-responsive nanocarriers have garnered significant attention and extensive research in drug delivery processes. CD Formulation supports developing intelligent liposomes using state-of-the-art technologies and expertise to create high-performance liposomes that respond to pH and redox.

Mechanism of pH-redox Responsive Liposomes

According to the research conducted, the pH of the tumor microenvironment (TME) is approximately 6.5. Compared to the extracellular pH of approximately 7.4 in tumor tissue, the difference is more pronounced in late endosomes and lysosomes (pH = 4.5-6.5). Therefore, pH is the most common stimulus factor in customizing stimulus-responsive nano drug delivery systems. In normal physiological conditions, charge-transfer nanoparticles (NPs) are neutral/negatively charged. However, when stimulated by reducing agents, pH, enzymes, reactive oxygen species (ROS), temperature, or light, their charge decreases, i.e., oxidation-reduction reactions, pH changes, enzymatic reactions, ROS generation, temperature changes, or light exposure occur. This allows for scalable circulation and improved tumor cell uptake. Thus, owing to the substantial disparities in intracellular and extracellular GSH concentration and pH levels, pH/redox dual-responsive nanocarriers may offer a crucial strategic approach for targeted delivery and intracellular release of therapeutic agents.

Fig.1 Illustrative diagram of pH/redox dual-responsive liposome mechanism.Fig.1 Illustrative diagram of pH-redox responsive liposome mechanism. (Badparvar, F., et al., 2023)

Our pH-redox Responsive Liposome Customization Service

Study on redox trigger mechanism

Lipids enclosed in liposomes typically contain triggerable moieties that govern the stability and permeability of the lipid bilayer. For example, the stability of disulfide bonds in nanocarrier structures is attributed to the low concentration of GSH in plasma, while cleavage of these bonds results in nanoparticle disintegration, leading to rapid cargo release due to high GSH concentration in plasma. Our services facilitate research on stimulus-responsive self-assembly structures by examining the formation and disruption of both covalent and non-covalent interactions at the nanoscale.

Study on pH response strategies

Two key features of the pH-triggered charge conversion method are (i) Protonation/deprotonation of surface groups on the nanocarrier; and (ii) Breaking of acid-labile bonds, which allows for faster response to pH changes without bond breaking. We provide ideas and strategies for our clients to develop novel pH-redox dual-responsive liposomes through this service.

Characterization and analysis

We offer a range of analyses for custom products not limited to the following service types.

  • Morphology
  • Characterization of pH-triggered charge transfer behavior of engineered liposomes
  • Both in vitro pH and ROX trigger the intracellular release of drugs
  • Intracellular uptake studies
  • apoptosis
  • Cell cycle arrest analysis
  • In vivo release study
  • In vivo targeting efficiency study
  • Drug distribution in vivo

Fig.2 Illustrative workflow of our customized pH-redox responsive liposome service.Fig.2 Illustrative diagram of customized pH-redox responsive liposome service. (CD Formulation)

Our Platforms for pH-redox Responsive Liposome Customization

Techniques and Platforms Specifics
pH-redox Responsive Development Platform
  • To support the study of the trigger mechanism of pH and redox stimuli.
  • Study on the binding strategy of trigger factor and liposome.
Product Application Platform
  • To support the development of levels and purity that are appropriate for specific application scenarios.
Characterization Platform
  • Physical and chemical characterization.
  • In vitro and in vivo characterization.
  • Advanced analytical instruments for in vitro and in vivo analysis.

Why Choose CD Formulation?

  • Smart pH/redox-responsive delivery system development platform. The platform supports pH-redox dual-responsive liposome formulation, process optimization, and analytical characterization.
  • Top teams. Our technical team is dedicated to the advancement of pH-redox dual-responsive liposomes and possesses extensive expertise and experience in this domain. The team members boast diverse backgrounds across multiple disciplines.
  • Powerful analytics platform. The platform is equipped with state-of-the-art analytical instruments for the verification of physical, in vitro, and in vivo analysis, systematically characterizing the quality of customized products.

Published Data

Technology: size-switchable intelligent nanovehicle technique

Journal: Scientific reports

IF: 3.8

Published: 2023

Results: In this study, (PAA-b-PCL-S-S-PCL-b-PAA) copolymerized nanoparticles (NPs) have size-switching capabilities and dual pH/ REDOX triggered drug release behavior, designed to significantly promote cancer uptake by MDA-MB-231 tumor cells (approximately 100% cell internalization within 30 minutes) and site-specific targeted doxorubicin (DOX) delivery. In conclusion, compared with free DOX, the dual pH/ REDOX reaction and size-switching DOX-supported NPs developed in this study have outstanding anti-tumor properties, which may provide a promising platform for tumor site-specific accumulation and drug release, and provide a basis for further in vivo studies.

Fig.3 Histogram of cell cycle distribution treated with liposomes.Fig.3 Histogram of cell cycle distribution for MDA-MB-231 cells treated with free DOX, DOX-loaded NPs, polymer NPs, and untreated cells. (Badparvar, F., et al., 2023)

With state-of-the-art technology and platforms, CD Formulation is dedicated to delivering intelligent pH/redox dual-responsive liposomes to our customers. If you require any assistance, please do not hesitate to contact us.

References

  1. Badparvar, F., Marjani, A.P., et al. pH/redox responsive size‐switchable intelligent nanovehicle for tumor microenvironment targeted DOX release. Sci Rep. 2023. 13, 22475.
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