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pH

The potential of hydrogen (pH) is a measure of the acidity or basicity of a water-based solution determined by the concentration of hydronium ions (H3O+). In one liter of pure water at neutral pH, there are 1×10−7 moles of hydronium ions. However, the extensive range of hydronium ion concentrations present in water-based solutions makes measuring pH in moles cumbersome. Therefore, a pH scale was developed to convert moles of hydronium ions into the negative logarithm of the hydronium...

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On-Chip Octanol-Assisted Liposome Assembly for Bioengineering

On-Chip Octanol-Assisted Liposome Assembly for Bioengineering

Published on: March 17, 2023

Tunable pH Sensitive Lipoplexes.

Hélène Dhotel¹, Michel Bessodes¹, Nathalie Mignet²

¹Université de Paris Cité, CNRS, INSERM, UTCBS, Unité des Technologies Chimiques et Biologiques pour la Santé, Faculté de Pharmacie, Paris, France.

Methods in Molecular Biology (Clifton, N.J.)

|February 13, 2023

Summary

Researchers developed pH-sensitive, anionic pegylated lipoplexes for gene delivery. These nanoparticles reduce clearance, increase blood circulation time, and enhance tumor accumulation for improved gene therapy.

Keywords:

Anionic cholesterol Anionic lipoplexes Gene delivery to tumor Pegylated lipoplexes pH-sensitive lipoplexes

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Microfluidic Production of Lysolipid-Containing Temperature-Sensitive Liposomes

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Area of Science:

Biotechnology
Nanomedicine
Gene Therapy

Background:

Gene delivery requires nanoparticles that circulate long enough to reach tumors.
Reducing positive charges on gene carriers can decrease elimination and increase circulation time.
Tumor accumulation of nanoparticles can be improved by longer blood circulation.

Purpose of the Study:

To design long-circulating, pH-sensitive nanoparticles for effective gene delivery to tumor cells.
To create anionic pegylated lipoplexes by combining cationic lipoplexes and pegylated anionic liposomes.
To optimize the lipid ratio for pH-sensitive charge neutralization within the 5.5-6.5 range.

Main Methods:

Formulation of anionic pegylated lipoplexes from cationic lipoplexes and pegylated anionic liposomes.
Monitoring of particle surface charge neutralization using dynamic light scattering as a function of pH.
Assessment of DNA compaction via Picogreen assay for DNA accessibility.
In vitro evaluation of transfection efficiency and pH sensitivity using bafilomycin.

Main Results:

Anionic pegylated lipoplexes were successfully prepared and demonstrated pH sensitivity between pH 5.5-6.5.
Particle surface charge neutralization was optimized by adjusting the anionic and cationic lipid ratio.
DNA compaction within the anionic complexes was confirmed.
In vitro studies showed effective transfection and confirmed the pH-sensitive properties.

Conclusions:

Anionic pegylated lipoplexes offer a promising platform for long-circulating gene delivery systems.
The designed nanoparticles exhibit pH sensitivity, crucial for targeted release in tumor microenvironments.
These findings support the potential of these lipoplexes for enhanced tumor accumulation and gene therapy efficacy.