Tumour targeting

Tumour targeting

1. TUMOUR TARGETING SIDDU K M 1 ST M PHARM DEPARTMENT OF PHARMACEUTICS AL AMEEN COLLEGE OF PHARMACY, BENGALURU

2. CONTENTS Introduction Difference between normal cell and cancer cell Stages of tumour development Tumour targeting Approaches for tumour targeting References 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 2

3. INTRODUCTION A tumour , also known as a neoplasm, is an abnormal mass of tissue that may be solid or fluid-filled . In general, tumours are divided into three groups : Benign:  These are not cancerous and cannot spread. A benign tumour will remain in its current form. They do not generally return after being removed. Premalignant:  A premalignant tumour is not yet cancerous but appears to be developing the properties of cancer. Malignant:  Malignant tumours are cancerous. They can grow, spread, and get worse. 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 3

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5. Difference Between Normal Cell And Cancer Cell NORMAL CELL TUMOUR CELL Cell repair & cell death Repair & apoptosis No repair & apoptosis Metastasize No Yes Rate of growth Controlled Uncontrolled Functioning Functional Non functional Angiogenesis Only when required for repair Always Mortality Mortal Immortal 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 5

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7. Stages Of Tumour Development 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 7

8. Tumour Targeting

9. Modified with targeting moieties, such as antibodies, antibody fragments, specific molecules, small peptides etc ., the carriers (nanoparticles) can  target specific receptors and antigens expressed exclusively or overexpressed on the tumour  cell surface or the  tumour  microenvironment, reducing side effects on normal  cells. TARGETED THERAPY TUMOUR TARGETING TARGETED DRUG DELIVERY 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 9

10. TARGETED THERAPY TARGETED DELIVERY It is a type of medication that blocks the growth of cancer cells by interfering with specific targets which are needed for carcinogenesis and tumor growth Refers to predominant drug accumulation within a target zone that is independent of the method and route of drug administration 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 10

11. APPROACHES FOR TUMOUR TARGETING PASSIVE TARGETING ACTIVE TARGETING TRIGGERED DRUG DELIVERY 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 11

12. PASSIVE TARGETING P assive targeting is based on drug accumulation in the areas around the tumours with leaky vasculature; commonly referred to as the enhanced permeation and retention (EPR) effect Passive targeting exploits the anatomical differences between normal and tumour tissue to deliver the drugs. Passive targeting involves transport of nanocarriers through leaky tumour capillary fenestrations into the tumour interstitium and cells by convection or passive diffusion & selective accumulation of nanocarriers and drug then occur by the EPR effect 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 12

13. Enhanced Permeability & Retention Effect The enhanced permeability and retention (EPR) effect is a unique phenomenon of solid tumors based on their anatomical and pathophysiological differences from normal tissues. M acromolecular drugs could accumulate and retain in solid tumor tissues selectively but they will not distribute much in normal tissue. EPR based chemotherapy is thus becoming an important strategy to improve the delivery of therapeutic agents to tumors for anticancer drug development. 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 13

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15. Examples : Approved Drugs Carrier Drug Name Indication Nano particles Doxorubicin Paclitaxel Transdrug Nanoxel Hepatocarcinoma Breast cancer Liposomes Doxorubicin Vincristine Myocet Marqibo Breast cancer Leukemia Polymeric micelles Paclitaxel Genexol -PM Breast , lung, pancreatic cancer 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 15

16. ACTIVE TARGETING Active targeting is used to describe specific interactions between drug/drug carrier and the target cells, usually through specific ligand–receptor interactions. A ctive targeting means a specific ligand–receptor type interaction for intracellular localization which occurs only after blood circulation and extravasation. Active drug targeting is generally implemented to improve target cell recognition and target cell uptake, and not to improve overall tumor accumulation. 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 16

17. Components of Active Targeting 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 17

18. Ligand mediated targeting is the major approach that involves ligands developed against cell receptors or antigenic determinants expressed on tumor cells or vasculature. Examples Folate Transferrin Lectins 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 18

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20. TRIGGERED DRUG DELIVERY The tumor microenvironment differs from that normal cells microenvironment. Advantage of the difference in pH, temperature and presence of enzymes is used to release the drug in the tumor microenvironment. p H sensitive drug release Enzyme activated conjugates Proteases External stimuli triggered (Magnetic field) 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 20

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22. References Targeted & controlled drug delivery Novel Carrier Systems by S P Vyas and R K Khar; 512- 557 Targeted drug delivery to tumours : Myths, reality and possibility https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272876/ Design of nanoparticle based carriers for targeted drug delivery https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936496/ 25-02-2019 Al Ameen College Of Pharmacy, Bengaluru 22

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