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Published on: June 28, 2021
Development and characterization of interleukin-18-loaded biodegradable microspheres
International Journal of Pharmaceutics
|March 7, 2006
Summary
Researchers developed biodegradable microspheres to deliver interleukin-18 (IL-18) directly into brain tumors, aiming to stimulate an anti-tumor immune response within the central nervous system (CNS). The S/O/W method showed optimal IL-18 release for potential glioma therapy.
Area of Science:
- Biomedical Engineering
- Immunology
- Neuro-oncology
Background:
- Malignant gliomas resist traditional immune responses within the central nervous system (CNS).
- Immunostimulation offers a strategy to eradicate cancer cells by harnessing the immune system.
- Interleukin-18 (IL-18) is a cytokine with known anti-tumor activity and immune-triggering properties.
Purpose of the Study:
- To develop and evaluate biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres for sustained delivery of IL-18 into CNS tumors.
- To optimize the encapsulation and in vitro release of active IL-18 from PLGA microspheres.
- To establish a reliable method for assessing IL-18 bioactivity post-encapsulation.
Main Methods:
- Development of PLGA microspheres for stereotactic implantation loaded with IL-18.
- Investigation of two encapsulation procedures: Water-in-Oil-in-Water (W/O/W) and Solid-in-Oil-in-Water (S/O/W).
- Assessment of IL-18 bioactivity using specific bioassays and verification of its stability during encapsulation.
- In vitro release studies using 125I-IL-18 and a continuous flow system to determine release profiles.
Main Results:
- The S/O/W encapsulation method yielded an optimal in vitro release profile for IL-18 from PLGA microspheres.
- S/O/W method demonstrated a moderate initial burst effect followed by sustained release of 16.5+/-8.4 ng/day over 21 days.
- The W/O/W method resulted in a lower sustained release of 6.1+/-4.2 ng/day.
- Analytical testing confirmed the stability and preserved biological activity of IL-18 after release from microspheres.
Conclusions:
- Biodegradable PLGA microspheres loaded with IL-18 are a viable strategy for localized immunotherapy in the CNS.
- The S/O/W encapsulation method is superior for achieving sustained and effective release of active IL-18.
- The developed system holds promise for in vivo evaluation and validation as a therapeutic approach for glioma treatment.
