pH-sensitive liposomes are advanced delivery systems engineered to release encapsulated drugs in response to changes in serum pH, thereby enhancing therapeutic efficacy. These liposomes effectively transport therapeutics, gene fragments, and reagents into cells via the endocytosis pathway. At CD Formulation, we leverage our extensive expertise in nanodelivery systems and proprietary nanoparticle technology to offer bespoke pH-sensitive liposome solutions, supporting researchers and pharmaceutical companies in their innovative pursuits.
As a drug carrier, liposomes have the characteristics of targeting and slow release, which can improve drug efficacy and reduce drug toxicity to a certain extent. Nevertheless, in comparison to conventional liposomes, there are still numerous limitations in their clinical application. At sites of tumor stroma, ischemic infection, or inflammation, pH is much lower than surrounding normal tissue. Based on the changes in pH value within pathological tissues, a novel type of liposome known as pH-sensitive liposome has been developed. This innovation offers significant advantages in targeted delivery and controlled drug release within cells. The membrane structure of pH-sensitive liposomes changes with the adjustment of pH from 7.4 to 5.3 to 6.3, which can cause the liposome membrane to fuse with the endosome membrane, thereby releasing water-soluble contents.
Fig.1 Schematic diagram of pH sensitivity of the anionic liposomes at acidic pH. (Aoki, Asami, et al., 2015)
The primary excipient in pH-sensitive liposomes is unsaturated phosphatidylethanolamine. In acidic environments, the carboxyl groups of the phosphatidylethanolamine become protonated, leading to a reduction in the three-dimensional volume of the hydrophilic side. This reduction ultimately destabilizes the liposome membrane and results in the release of encapsulated biologically active molecules. Commonly used polymorphic lipids for pH-sensitive liposome preparation are referred to unsaturated phosphatidyl ethanolamine (PE). We can offer screening of lipids such as diacetylphosphatidyl ethanolamine (DAPE), palmitoyl oleoylphosphatidyl ethanolamine (POPE), dioleylphosphatidyl ethanolamine (DOPE), citracony-dioleoyl-phosphatidyl-ethanolamine (C-DOPE), N-citraconyl-dioleoyl-phosphatidylserine (C-DOPS), etc.
This service assists clients in the development of pH-sensitive liposomes by incorporating pH-sensitive peptides/proteins into the liposomal structure. Examples of such pH-sensitive peptides/proteins include GALA, hemin (influenza INF peptide) N-terminal, or Listeriolysin O inserted into phospholipid double fusion peptide or protein. In a neutral pH environment, the peptide or protein remains inactive; however, in an acidic environment, the conformational change of the fusion peptide or protein promotes membrane fusion between the liposome and cell membrane, ultimately leading to content release.
Currently, polymers used for pH-sensitive liposome design include poly alkyl acrylics, succinylated PEG, and N-isopropylacrylamide (NIPAM) copolymers. We are also researching the use of alternative polymers to construct pH-responsive liposomes.
Fig.2 Schematic diagram of our workflow for pH-sensitive liposome customization. (CD Formulation)
We have established a proprietary platform for the development of pH-sensitive liposomes and can offer the following technologies:
Techniques and Platforms | Specifics |
pH-sensitive Triggering Molecule Screening Platform |
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In Vitro Characterization Platform |
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Mechanisms Study Platform of Intracellular Delivery Mediated by pH-sensitive Liposomes |
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Application Development Platform of pH-sensitive Liposomes |
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Drug Delivery | Anti-tumor, anti-inflammatory |
Gene Therapy | Active targeting technology Non-viral vector |
Biomedical Science | pH biosensors, cell diagnostic reagents |
Imaging | MRI contrast agents |
Vaccine | Vaccine adjuvants |
Technology: Programmed liposome and PH-sensitive liposome techniques
Journal: J Nanobiotechnol
IF: 10.2
Published: 2019
Results: This paper describes a programmed release drug delivery system that avoids drug efflux and nuclear transport through a simple nanostructured drug strategy. Liposome-based nanostructured drugs (LNSD) based on programmed liposomes consist of two modules: doxorubicin (DOX) is loaded into tetrahedral DNA (TD, ~ 10 nm) to form small nanostructured DOX, and the nanostructured DOX is encapsulated into PH-sensitive liposomes. In vitro and in vivo studies have shown multiple benefits for the treatment of drug-resistant tumors:
(1) It not only enhances the uptake of DOX by cells but also maintains the optimal concentration of DOX in drug-resistant tumor cells through the anti-efflux effect induced by nanostructures.
(2) Small nanostructured DOX enters the nucleus effectively through size-dependent nuclear transport and is treated intensively.
(3) Improving pharmacokinetics and biodistribution by reducing the leakage of DOX during circulation. The system developed in this study has the potential to provide new treatments for drug-resistant tumors.
Fig.3 Mechanism of ultrasmall nanostructured drug-based pH-sensitive liposome for effective treatment of tumor. (Zhanwei Zhou, et al., 2019)
CD Formulation has established a specialized platform for the development of pH-sensitive liposomes in order to offer customers a wide range of highly effective pH-sensitive liposome products. Please do not hesitate to contact us if you require any assistance.
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