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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
Clusterin antisense complexed with chitosan for controlled intratumoral delivery
Christopher M Springate1, John K Jackson, Martin E Gleave
1Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
International Journal of Pharmaceutics
|September 25, 2007
Summary
This study developed an injectable delivery system for clusterin antisense oligonucleotide (ASO) using chitosan microparticles and a polymeric paste. The system provides controlled release and maintains clusterin ASO bioactivity, inhibiting cancer protein expression.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Cancer Therapeutics
Background:
- Antisense oligonucleotides (ASOs) offer targeted gene silencing for therapeutic applications.
- Developing effective delivery systems is crucial for ASO stability and efficacy.
- Clusterin is a protein implicated in cancer progression, making it a target for ASO therapy.
Purpose of the Study:
- To characterize an injectable, controlled-release delivery system for clusterin antisense oligonucleotide (ASO).
- To investigate the impact of clusterin ASO/chitosan ratio on microparticle properties and ASO release.
- To evaluate the stability and bioactivity of clusterin ASO within the developed formulation.
Main Methods:
- Complexation of clusterin ASO with chitosan microparticles (CC complexes).
- Blending CC complexes with a biodegradable polymeric paste (CC in paste).
- In vitro release studies in PBS and plasma, stability assessments, and cell-based assays (PC-3 cells).
Main Results:
- Chitosan microparticles exhibited pH-dependent swelling and zeta potential changes.
- Increased chitosan content and lower pH enhanced clusterin ASO complexation.
- The formulation demonstrated a burst release followed by sustained release of clusterin ASO.
- Inclusion in the polymeric paste protected clusterin ASO from plasma degradation and maintained bioactivity, inhibiting clusterin protein expression by 52-62%.
Conclusions:
- The developed injectable system enables controlled and sustained release of bioactive clusterin ASO.
- Formulation parameters like chitosan ratio and pH significantly influence ASO loading and release kinetics.
- This delivery system shows promise for intratumoral gene silencing therapies.
