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Xu wenting

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Xu wenting

  1. 1. A study on the development of mucoadhesive targeting liposomes<br />Wenting Xu<br />Department of Pharmaceutical Engineering<br />2011.6.2<br />
  2. 2. Aims of the study<br /><ul><li>Development of folate-tethered mucoadhesive liposomes containing polymeric drug
  3. 3. To improve gastrointestinal absorption of hydrophilic polymer drug</li></li></ul><li>Ideas of the study<br /><ul><li>Approach 1: Increase of the rigidity of liposomal membrane </li></ul>DSPC Vs EPC liposomes<br /><ul><li>Approach 2: Increase of mucoadhesion of liposomes by coating with chitosan
  4. 4. Approach 3: Enhanced intestinal absoption of liposomes through folate transport system(Folate-PEG)</li></li></ul><li>Introduction<br />
  5. 5. What is a Liposome?<br /><ul><li>Vesicles made of lipid bilayer
  6. 6. In drug delivery system:
  7. 7. Bilayer: </li></ul>Hydrophobic drugs<br /><ul><li>Inside of liposomes:</li></ul>Hydrophilic drugs<br />
  8. 8. Basic composition of liposomes<br /><ul><li>Phospholipid
  9. 9. Cholesterol</li></li></ul><li>Phospholipids<br />EPC<br />(Egg phosphatidylcholine)<br />DSPC <br />(Distearoyl phosphatidyl choline)<br />Fatty acid chain<br />16:0-18:1<br />Fatty acid chain<br />18:0-18:0<br />
  10. 10. EPC &DSPC<br />
  11. 11. Cholesterol<br />Fluidityreduction<br />Hydrophilic<br />Hydrophobic<br />
  12. 12. Liposome/Cell Interaction <br />Adsoption<br />Fusion<br />Endocytosis<br />Lipid transfer<br />
  13. 13. Modification of liposomal surface<br /><ul><li>Protection of drug
  14. 14. Avoidance of RES</li></ul>(reticuloendothelial system)<br /><ul><li>Extended release
  15. 15. Targeting </li></li></ul><li>Mucoadhesion<br /> <br />Mucoadhesion<br /><ul><li>Attachment to a biological substrate</li></ul>Mucous gel layer<br /><ul><li>Increasing residence time of liposomes
  16. 16. Mucin</li></li></ul><li>Chitosan<br /><ul><li>Nontoxic
  17. 17. Mucinrecognitivemolecules
  18. 18. Chitosan-coatingliposome</li></ul>Liposome (-):A<br /> Chitosan(+):B<br />
  19. 19. Folate-conjugated liposomes<br />Intestinal absorption enhancement :<br />? Through folate transport system<br /> in brush border membrane <br />
  20. 20. FITC-dextran 3k <br />As a model drug mimicking peptide drug such as calcitonin <br /><ul><li>High sensitivity</li></ul>Concentrations down to 1ng/ml <br />can be detected in tissue fluids<br />
  21. 21. Experiments &Results<br />
  22. 22. Preparation of liposomes<br />
  23. 23. Composition of liposomes<br />
  24. 24. Preparation of Liposomes<br />Liposome suspension<br />
  25. 25. Preparation of Liposomes<br />Extrusion through 0.4um and then 0.2um membrane <br />
  26. 26. Removal of unencapsulated dextran- 3K<br />Dialysis<br />
  27. 27. Encapsulation efficiency <br />
  28. 28. Encapsulation efficiency<br /> Encapsulation efficiency =<br />Drug-to-phosphate ratio measured after dialysis<br />×100%<br />Drug-to-phosphate ratio of loading<br />
  29. 29. Encapsulation efficiency <br />Result:<br />
  30. 30. Uptake by Caco2 cell<br />
  31. 31. Uptake by Caco2 cell<br />The Caco-2 cell line <br /><ul><li>Derived from colon cancer cell
  32. 32. Known to have similar characteristics with the small intestinal</li></ul>epithelial cells <br /><ul><li>Can be used as HTSS for studing the drug uptake in instestine</li></ul> Hamilton test simulation system<br />
  33. 33. Uptake by Caco2 cell<br />Cell culture<br /><ul><li>Folate-free RPMI 1640 medium </li></ul>Folate receptoroverexpressed (2 weeks)·<br /><ul><li>Folate medium RPMI 1640 medium</li></ul>To study folate receptor mediated transport<br />
  34. 34. Procedure of Caco2 cell uptake experiment<br />
  35. 35. Result of Caco2 cell uptake experiment<br />
  36. 36. Mucoadhesion studies&<br />Evaluation of the absorption <br />of liposomes<br />
  37. 37. In vivo experiment<br />
  38. 38. Result of mucoadhesionstudies<br />
  39. 39. Blood dextran 3k concentration<br />
  40. 40. Conclusion<br />
  41. 41. <ul><li>Approach 1: Increase of the rigidity of liposomal membrane(DSPC)
  42. 42. DSPC significantly increased the drug retention in mucosal layer of intestine and blood drug concentration
  43. 43. Approach 2: Increase of the mucoadhesion of liposomes(Chitosan)
  44. 44. Modification with chitosan could not increase the mucoadhesion of liposomes (might be due to the bigger size and breaking the liposomes)
  45. 45. Approach 3: Enhanced intestinal absoption of liposomes</li></ul>through folate transport system(Folate-PEG)<br /><ul><li>Modification with folate could not increase the intestinal absoption of liposomes</li></li></ul><li>Thank you !<br />

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