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Updated: Jun 6, 2026
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Enhanced Gene Delivery and Expression using Intraosseous Injection of Chitosan Nanoparticles Encapsulated Adenine Base Editor Plasmids
Published on: May 16, 2025
Chondroitin sulfate capsule system for efficient and secure gene delivery
Tomoaki Kurosaki1, Takashi Kitahara, Shintaro Fumoto
1Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
Summary
Chondroitin sulfate (CS) enhances gene delivery by forming stable ternary complexes. These CS-encapsulated polyplexes show targeted spleen delivery and reduced toxicity, indicating potential for safe gene therapy.
Area of Science:
- Biomaterials Science
- Gene Therapy
- Nanotechnology
Background:
- Gene delivery systems face challenges with efficiency and safety.
- Cationic polyplexes and lipoplexes show promise but often exhibit high cytotoxicity and agglutination.
- Developing safer and more effective delivery vectors is crucial for advancing gene therapy.
Purpose of the Study:
- To develop and evaluate ternary complexes of polyplexes and lipoplexes encapsulated with chondroitin sulfate (CS) for gene delivery.
- To investigate the universal applicability of these CS-based complexes for gene delivery applications.
- To assess the in vitro and in vivo performance, including transfection efficiency, cytotoxicity, and hematotoxicity.
Main Methods:
- Preparation of cationic complexes using pDNA with poly-L-arginine, poly-L-lysine, or DOTMA-based liposomes.
- Formation of ternary complexes by encapsulating cationic complexes with chondroitin sulfate (CS).
- Evaluation of in vitro transfection efficiency in B16-F10 cells, cytotoxicity, and erythrocyte agglutination.
- Assessment of in vivo transfection efficiency in mice, particularly after intravenous administration.
Main Results:
- Cationic complexes demonstrated high in vitro transgene efficiency but also significant cytotoxicity and erythrocyte agglutination.
- CS encapsulation yielded stable ternary complexes with improved in vitro transfection efficiency, reduced cytotoxicity, and minimal agglutination.
- In vivo studies showed CS-encapsulated polyplexes achieved high, targeted transgene efficiency in the spleen following intravenous administration.
- CS encapsulation, however, diminished the transgene efficiency of lipoplexes.
Conclusions:
- Chondroitin sulfate (CS) effectively stabilizes polyplexes and lipoplexes, improving their safety profile for gene delivery.
- CS-mediated encapsulation offers a strategy for targeted gene delivery, particularly to the spleen, with reduced adverse effects.
- CS holds significant potential as a component in developing safe and effective polyplex-based gene delivery systems for therapeutic applications.
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