pH-responsive biodegradable assemblies containing tunable phenyl-substituted vinyl ethers for use as efficient gene...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Developing effective nonviral gene delivery systems remains a challenge.
• pH-responsive materials offer potential for targeted drug and gene release.
• Existing systems often face limitations in transfection efficiency and cytotoxicity.

Purpose of the Study:

• To create novel pH-responsive liposomes utilizing phenyl-substituted vinyl ether (PIVE) cross-linkers.
• To investigate the pH-dependent hydrolysis and dePEGylation of these assemblies.
• To evaluate the in vitro transfection efficiency and cytotoxicity of the developed liposomes.

Main Methods:

• Preparation of PEG-lipid:DOPE liposomes incorporating PIVE cross-linkers.
• Hydrolysis studies of PIVE linkages at various acidic pH conditions (4.2, 5.4, 7.4).
• In vitro transfection assays using HEK 293 and COS-7 cells, comparing with polyethylenimine (PEI).

Main Results:

• PIVE hydrolysis rate and dePEGylation were found to be pH-dependent, influenced by phenyl ring substitutions.
• The pH-responsive assemblies demonstrated controlled content release triggered by acidic conditions.
• Higher transfection efficiency and lower cytotoxicity were observed for PEG-PIVE-lipid:DOPE liposomes compared to PEI.

Conclusions:

• Novel pH-sensitive PIVE linkages enable controlled dePEGylative triggering and content release from liposomes.
• PEG-PIVE-lipid:DOPE liposomes represent a promising nonviral vehicle for gene and drug delivery applications.
• The developed system offers a potential alternative to existing gene delivery vectors with improved safety and efficacy profiles.