pH-responsive Liposome Development Service
Introduction Preparation Applications
pH-responsive liposomes are designed to release their contents in response to changes in pH, making them particularly suitable for drug delivery in the acidic tumor microenvironment. Creative Biolabs can provide customized solutions for pH-responsive liposomes, dedicated to enhancing targeted drug delivery and improving therapeutic efficacy in challenging environments.
What are pH-responsive Liposomes?
pH-responsive liposomes, also known as pH-sensitive liposomes, maintain stability at physiological pH while becoming unstable in low pH environments, which triggers drug release. They possess advantages such as endosomal/lysosomal escape, targeting ability, and sustained release, and are commonly employed as smart drug delivery systems. Different parts of the human body exhibit varying pH levels: the pH of normal tissue and blood is around 7.4; that of endosomes and lysosomes ranges from 4.5 to 5.5; within tumor tissues, the pH typically falls between 6.7 and 7.2 due to the high glycolytic activity of tumor cells converting glucose into lactic acid; The pH levels in regions such as the stomach, large intestine, and small intestine are approximately 0.9-1.5, 8.3-8.4, and 7.6, respectively. By leveraging these differences in pH across various tissues, pH-responsive liposomes can enhance drug release at specific sites, reduce release in normal cells, minimize side effects, and improve bioavailability.
Fig.1 The pH-sensitive liposomes in cancer drug delivery.1, 2
Preparation of pH-responsive Liposomes
The differences in the preparation methods of pH-sensitive liposomes compared to conventional liposomes primarily depend on the specific pH-sensitive materials used. These pH-sensitive materials include pH-sensitive lipids, pH-sensitive polymers, and pH-sensitive peptides. Depending on the composition of the materials used in the pH-sensitive liposomes, they exhibit different response mechanisms:
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Introduction of pH-sensitive liposomes with protonatable groups
H-sensitive liposomes are typically composed of neutral DOPE and amphiphilic substances containing protonatable acidic groups, such as oleic acid (OA), and cholesteryl hemisuccinate (CHEMS). DOPE exhibits an unstable inverted hexagonal structure when present alone, making it unable to form stable liposomes. At physiological pH, the negatively charged carboxyl groups of CHEMS experience electrostatic repulsion from the positively charged amines in DOPE, allowing CHEMS to insert between DOPE molecules and form a complementary structure that stabilizes the liposomes. When the pH decreases, the protonation of the carboxyl groups in CHEMS disrupts this structure, inducing DOPE to revert to the hexagonal phase, which in turn leads to the destabilization of the liposomes or their fusion with endosomes to release the drug.
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Introduction of pH-sensitive liposomes with acid-sensitive bonds
The introduction of acid-sensitive bonds into liposomal structures ensures that they remain intact in neutral or alkaline environments but undergo cleavage upon exposure to the acidic tumor microenvironment, thereby releasing the encapsulated drug and exerting a therapeutic effect. Common types of acid-sensitive bonds include hydrazone bonds, imine bonds, and amide bonds. Hydrazone bonds are typically synthesized through a condensation reaction between aldehyde/ketone carbonyl groups and hydrazine, and they exhibit rapid hydrolysis under acidic conditions (pH 5.0–6.0), offering moderate sensitivity.
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Introduction of pH-sensitive liposomes with pH-sensitive peptides
Peptides with different structures exhibit varied functions. Modifying liposomes with pH-sensitive peptides can facilitate drug release in acidic environments. The transmembrane and insertion regions of the pH-low insertion peptides contain numerous acidic residues. At physiological pH levels, the peptide adopts a coiled conformation with a negative charge, maintaining a hydrophilic state that prevents it from penetrating the lipid bilayer. However, in an acidic environment, the protonated peptide exhibits neutralized charges, transitions into an α-helical structure, and shifts to a more neutral, lipophilic state, thereby anchoring itself as a transmembrane protein within the lipid bilayer.
Commonly used pH-sensitive materials are as follows:
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pH-sensitive Component (Lipid/polymer/peptide)
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DOPE
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POPE
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DDAB
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Diolein
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Succinylated poly(glycidol) (SucPG)
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Cholesteryl hemisuccinate (CHEMS)
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Alkylated N isopropylacrylamide (NIPAM)
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Palmitoyl homocysteine (PHC)
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Oleic acid-PEG-poly(monomethylitaconate)-CholC6 (PEG-PMMI-CholC6)
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GALA peptide
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STP peptide
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Applications of pH-responsive Liposomes
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Tumor targeting
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Nucleic acid delivery
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Immunoliposomes
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Multiple response
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Medical dressings
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Imaging
Elevate your drug delivery strategies with Creative Biolabs' pioneering pH-responsive liposomes. At the forefront of smart delivery systems, our multidisciplinary team of experts in raw material synthesis and formulation development collaborates seamlessly to advance your projects. Contact us today to transform your research and development with our innovative solutions.
References
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Ashrafizadeh, Milad, et al. "Stimuli-responsive liposomal nanoformulations in cancer therapy: Pre-clinical & clinical approaches." Journal of controlled release 351 (2022): 50-80.
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Distributed under Open Access license CC BY 4.0, without modification.
For Research Use Only. Not For Clinical Use
