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CN4218 Review of Doxorubicin Literature

CN4218 Review of Doxorubicin Literature. Cheong Chong You Koh Bei Wei Lee Wen Qi Wesley Ng. Group 9. 1. Introduction. What is Doxorubicin?. Cancer Therapy Drug Discovered and popularized in the 1970s . Cancer Killing Properties

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CN4218 Review of Doxorubicin Literature

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  1. CN4218Review of Doxorubicin Literature Cheong Chong You Koh Bei Wei Lee Wen Qi Wesley Ng Group 9

  2. 1 Introduction

  3. What is Doxorubicin? Cancer Therapy Drug Discovered and popularized in the 1970s. Cancer Killing Properties Releases reactive oxygen species (ROS) which generates high amounts of oxidative stress, lipid peroxidation, membrane and protein damage, DNA damage and most importantly facilitates pathways leading to cell death

  4. Common Applications

  5. Problems of Doxorubicin – Non-specific Cytotoxicity Cardiotoxicity • DOX causes cardiomyopathy and congestive heart failure upon chronic administration. • Specifically, DOX was shown to induce cytotoxicity to cardiovascular systems through mainly reactive oxygen species (ROS) induced apoptosis. Hepatotoxicity • Hepatotoxicity induced by DOX acts upon similar mechanisms of oxidative stress and free radical release which cause irreversible damage to cellular systems. Pulmonary Toxicity • It is postulated that pulmonary toxicity manifests much like cardiotoxicity and hepatotoxicity through ROS-induced apoptosis and release of free radicals. • Lung injuries sustained from DOX have been reported to show high severity where 10% of patients develop adult respiratory distress syndrome (ARDS)

  6. How does particle technology help??? Through particle technology research, we are able to develop new drug delivery systems for DOX which have: • High loading efficiency • High biocompatibility and biodegradability • Capacity for controlled, and sustained release • TARGETED release

  7. 2 Summary of Characteristics of Each Delivery Systems

  8. Hollow Mesoporous Silica Nanospheres • 40% release at pH 4.3, 10% at pH 7.2 over 16 days. • Requires 10 times less DOX for same cell viability. • MSNs have super-high drug loading capacity (> 1 gram drug per gram silica)

  9. Chitosan Magnetic Nano-Particles (CS MNP) • 75% release at pH 4.2, 50% release at pH 5.0 over 15 hours. 20% release at pH 7.4, up to 200 hours. • IC50 of 13.5 µM for DOX-loaded CS MNPs compared to 176 µM for free Dox. • 13-fold efficiency for MCF-7R compared to free DOX.

  10. Multifunctional Aptamer-based Nanoparticles • More drug release at pH 5 than 7.4. • Higher cytotoxicity on MCF-7R than free DOX at doses greater than 0.1 µM. • Better than free DOX in terms to reducing cell clonogenicity. • Reduced cytotoxicity effect on normal liver cells.

  11. PEGylated PLGA Nanoparticles • Higher cytotoxicity compared to free DOX at doses greater than 10µM. Similar performance below 10 µM. • Less cardiotoxicity compared to DOX, DOXIL and PEG.

  12. Stimuli-Responsive Hydrogel • Ability to maintain a sustained release of DOX for up to 15 days • Reduces cell viability to approximately 20% at concentrations of 1 µg/ml and beyond.

  13. DOX-Mic + TRAIL Co-delivery System • 40% more drug release at pH 5.6 than 7.4 • DOX-Mic + TRAIL has significantly higher cytotoxicity on SW-480 than just DOX-Mic at 10mg/l after 48 hours incubation • DOX-Mic + TRAIL decreases clonogenicity of SW480 cells 

  14. 3 Conclusion

  15. Conclusion Nanoparticles • Targeted delivery systems • Rapid, pH dependent release Hydrogels • Sustained release • pH independent release(for pH 2-12) Problems to Overcome: • Nanotoxicity • Limited biodegradability • Biocompatibility (Immune Response) • Stability & solubility of carrier drugs • Effects of carrier drugs on pharmacokinetic properties of DOX • Selection of appropriate particle sizes

  16. QUESTIONS?

  17. THE END

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