The Development And Application Of Polymeric Micelles In The Tumor Targeted Drug Delivery System
1. The Development and Application of Polymeric Micelles in the Tumor-Targeted Drug Delivery SystemYunpeng FengIndustrial PharmacySt John’s University
2. INTRODUCTION PREPARATION AND DRUG LOADING BIOLOGICAL SIGIFINANCE TARGETING MECHANISMS CONCLUSIONS AND FUTURE DIRECTION
3. Introduction Cancer is a group of disease characterized by unregulated cell growth and spread of cell from primary site to other sites of the body Six Hallmarks of Cancer Growth Signal Autonomy Evasion of Growth Inhibitory Signal Evasion of Apoptosis ( programmed cell death) Unlimited Replicative Potential Angiogenesis ( formation of new blood vessel) Invasion and Metastasis
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5. Perhaps the greatest immediate impact of nanotechnologies in the cancer therapy is in the realm of drug delivery
6. Nanomedicine: drug delivery systems in a nanometer size containing encapsulated, dispersed, adsorbed, or conjugated drugs and imaging agents.
11. Methods: ring-opening polymerization, free-radical polymerization, step condensation, modified nanoprecipitation method, and solvent polymerization Graft the hydrophobic part Graft copolymer
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13. Effective targeting payload drug to the tumor site via passive and/ or active mechanisms
14. Volume of distribution and toxicity of drug are reduced due to the restricting distribution to the targeting sites.
15. Indeed, the PMs are large enough to avoid the renal clearance(>10nm) and bypass the filtration by interendothelial cell slits in the spleen( <200nm)
19. Preparation and Drug Loading If the polymer is not readily soluble in water, dialysis, oil in water emulsion, solid dispersion, microphase method, etc can be used. a. Process of Dialysis
25. Fast drug release will also cause the insufficient time for polymeric micelles to accumulate at the tumor sites
26. Slow drug release from PMs allows accumulation of polymeric micelles at target sites due to the depot effect
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28. Enhanced Permeation and Retention Effect (EPR Effect) The Difference between normal tissue and tumor tissue to illustrate the EPR effect (Passive Targeting)
29. The Limitation of EPR Effect EPR effect can be observed in almost all human cancers with the exception of hypovascular tumors such as prostate cancer or pancreatic cancer The passive targeting depends on the degree of tumor vascularization and angiogenesis Extravasation of nanocarriers will vary with tumor types and anatomical sites The high interstitial fluid pressure of solid tumors avoids successful uptake and homogenous distribution of drugs in the tumor The high interstitial fluid pressure (IFP) of tumors associated with the poor lymphatic drainage explain the size relationship with the EPR effect: larger and long-circulating nanocarriers are more retained in the tumor, whereas smaller molecules easily diffuse
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31. In this strategy, the enhanced cellular internalization rather than increasing accumulation at the tumor sites is mainly responsible of the anti-tumoral efficacy
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33. The ligand can direct possible bind to its receptor after intravenous injection
34. Compared to tumor cells, endothelial cells is more genetically stable, which will reduce the potential risk of emerging resistance