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Published on: November 29, 2018
Characterization of a microsphere formulation containing glucose oxidase and its in vivo efficacy in a murine solid
Qun Liu1, Andrew Michael Rauth, Jiang Liu
1Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario, M5S 3M2, Canada.
Purpose:
This work focused on the characterization and in vitro/in vivo evaluation of an alginate/chitosan microsphere (ACMS) formulation of glucose oxidase (GOX) for the locoregional delivery of reactive oxygen species for the treatment of solid tumors.
Methods:
The GOX distribution and ACMS composition were determined by confocal laser scanning microscopy and X-ray photoelectron spectroscopy. The mechanism of GOX loading and GOX-polymer interactions were examined with Fourier transform infrared spectroscopy and differential scanning calorimetry. In vitro cytotoxicity and in vivo efficacy of GOX-encapsulated ACMS (ACMS-GOX) were evaluated in EMT6 breast cancer cells and solid tumors.
Results:
GOX was loaded into calcium alginate (CaAlg) gel beads via electrostatic interaction and the CaAlg-GOX-chitosan complexation likely stabilized GOX. Higher concentrations of GOX near the surface of ACMS were detected. GOX retained its integrity upon adsorption to CaAlg gel beads during the coating and after release from ACMS. ACMS-GOX exhibited cytotoxicity to the breast cancer cells in vitro and their efficacy increased with increasing incubation time. Intratumorally delivered ACMS-GOX significantly delayed tumor growth with much lower general toxicity than free GOX.
Conclusion:
The results suggest that the ACMS-GOX formulation has the potential for the intratumoral delivery of therapeutic proteins to treat solid tumors.
Insights
Alginate/chitosan microspheres (ACMS) loaded with glucose oxidase (GOX) show potential for solid tumor treatment. This formulation enables locoregional delivery of reactive oxygen species, demonstrating efficacy in vitro and in vivo with reduced toxicity.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Cancer Therapeutics
Background:
- Solid tumors present challenges for conventional therapies.
- Locoregional delivery of therapeutic agents can improve efficacy and reduce systemic toxicity.
- Reactive oxygen species (ROS) have shown promise in cancer treatment.
Purpose of the Study:
- To characterize and evaluate an alginate/chitosan microsphere (ACMS) formulation of glucose oxidase (GOX).
- To assess the potential of ACMS-GOX for locoregional delivery of ROS for solid tumor treatment.
- To evaluate the in vitro and in vivo performance of the ACMS-GOX formulation.
Main Methods:
- Microsphere composition and GOX distribution analyzed using confocal microscopy and X-ray photoelectron spectroscopy.
- GOX loading mechanism and polymer interactions studied via Fourier transform infrared spectroscopy and differential scanning calorimetry.
- In vitro cytotoxicity and in vivo anti-tumor efficacy evaluated in breast cancer cells and solid tumors.
Main Results:
- Glucose oxidase (GOX) was successfully loaded into alginate/chitosan microspheres (ACMS) via electrostatic interactions, with higher GOX concentrations detected near the microsphere surface.
- ACMS-GOX demonstrated significant in vitro cytotoxicity against breast cancer cells, with efficacy increasing over time.
- Intratumoral administration of ACMS-GOX effectively delayed tumor growth in vivo, exhibiting substantially lower general toxicity compared to free GOX.
Conclusions:
- The developed alginate/chitosan microsphere formulation (ACMS-GOX) is a promising platform for the intratumoral delivery of therapeutic proteins.
- This formulation facilitates locoregional delivery of reactive oxygen species for potential solid tumor treatment.
- ACMS-GOX offers a potentially safer and more effective approach for cancer therapy compared to free drug administration.
