Resealed erythrocytes

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Resealed erythrocytes

  1. 1. Presentation byPresentation by SUNILBOREDDYSUNILBOREDDY (M. Pharmacy)(M. Pharmacy) Resealed ErythrocyteResealed Erythrocyte As Drug CarrierAs Drug Carrier
  2. 2. Content Introduction Erythrocytes as drug carrier Basic concept of erythrocytes Advantages & limitation Source & Isolation of Erythrocytes Method of drug Loading Characterization Drug release, Storage Application Conclusion
  3. 3. INTRODUCTION Current Research: Aimed at development of drug delivery system to get max. therapeutic effect. Idea of drug carrier system:to get maximum therapeutic effects, Elimination of undesirable side effects and Increase patient compliance. Magic Bullet Concept: Paul Ehrlich proposed. Decrease toxic effect and increase therapeutic effect to the targeted cell.
  4. 4. Resealed Erythrocytes Properties as carrier :- Appropriate size, shape to permit passage through the capillaries. Biocompatible & minimum toxic side effects Minimum leakage before target site is achieved Should be able to carry broad spectrum of drugs Appreciable stability during storage period Should have sufficient space & should carry adequate amounts of drugs
  5. 5. Erythrocytes Erythro= red Cytes = cell Biconcave discs, anucleate. Filled with hemoglobin (Hb), a protein that functions in gas transport Contain the plasma membrane protein spectrin and other proteins that: Give erythrocytes their flexibility Allow them to change shape as necessary
  6. 6. Erythrocytes CHEMICAL CONSTITUENTS: Water(63%) Lipid(0.5%) Glucose(0.8%) Minerals(0.7%) Non-hemoglobin protiens(0.9%) Methehemoglobin(0.5%) and Hemoglobin (33.67%)
  7. 7. Erythrocytes Healthy adult male= 4.5 millions/µml Healthy adult female= 4.8 millions/µml Matured RBCs have no nucleus Ribosome & Mitochondria . Therefore all space is available for drug carrier. Reticulocytes- immature erythrocytes
  8. 8. Advantages of erythrocyte as carrier:- Biodegradable Isolation is easy Non immunogenic large volume of drug can be encapsulated in small volume of erythrocytes Prolong systemic activity of drug Protection from premature degration Prodrug concept (Bioreactor) ReduceAdverse Effect Peptide & Enzyme Delivery Disadvantages :- Possibility of Leakage of cells & dose dumping Molecule Alter Physiology Of cell
  9. 9. Source, fractionation & isolation of erythrocytes Source:- mice, cattle, pig, dog, sheep, goat, monkey, chicken, rat, rabbit & human Whole blood can be collected by venipuncture or from orbital sinus in heparinized tube Red blood cells can be harvested & centrifuged(2500rpm/5min at 40 c . Different centrifugal force & different buffer composition(PBS,pH7.4) for different species is used Fresh blood is used for loading of drugs.
  10. 10. Methods Of Drug Loading InMethods Of Drug Loading In ErythrocytesErythrocytes 1. Hypo-osmotic lyses method a) Dilution method b) Dialysis method c) Pre-swell method d) Isotonic osmotic lyses method 2. Electric breakdown method 3. Endocytosis method 4. Membrane perturbation method 5. Normal transport method 6. Lipid fusion method
  11. 11. Dilutional Haemolysis RBC Membrane ruptured RBC Loaded RBC Resealed Loaded RBC 0.4% NaCl Hypotonic Drug Loading buffer Resealing buffer Incubation at 250 c Efficiency  1-8% Enzymes delivery Hypotonic med Isotonic med. Washed
  12. 12. Isotonic Osmotic Lysis RBC Isotonically ruptured RBC Chemical – urea, polyethylene, polypropylene, and NH4Cl Physical rupturing Chemical rupturing Drug Isotonic Buffer Loaded RBC Resealed RBC Incubation at 250 C
  13. 13. Preswell Dilutional Haemolysis RBC 0.6%w/v NaCl Swelled RBC Drug + Loading buffer 5 min incubation at 0 0 c Loaded RBC Incubation at 25 0 c Resealing Buffer Resealed RBC Efficiency  72% Fig:- Preswell Method
  14. 14. Dialysis RBC Phosphate buffer + 80 % Haematocri t value Placed in dialysis bag with air bubble Dialysis bag placed in 200ml of lysis buffer with mechanical rotator 2hrs. 4c. DrugLoading buffer Loaded RBCDialysis bag placed in Resealing buffer with mechanical rotator 30 min 37c. Resealed RBC Efficiency  30-45%
  15. 15. Entrapment by Endocytosis RBC Drug Suspension + Buffer containing ATP, MgCl2, and CaCl2 At 250 C Loaded RBC Resealing Buffer Resealed RBC Fig;- Entrapment By Endocytos Method
  16. 16. Membrane perturbation method RBC Amphotericin B e.g. Chemical agents Increased permeability of RBC Resealing Buffer Drug Resealed RBC
  17. 17. In vitro characterizationIn vitro characterization
  18. 18. In vitro characterization
  19. 19. Mechanism of release of resealed erythrocytes Shelf & storage stability of resealed erythrocytes In vivo survival & immunological consequences Some Important Aspects Of Resealed Erythrocytes
  20. 20. Applications of resealed erythrocytes Erythrocytes as carrier for enzymes Erythrocytes as carrier for drugs Erythrocytes for drug targeting Drug targeting to reticuloendothelial system Drug targeting to liver -Treatment of liver tumors -Treatment of parasitic diseases -Removal of RES iron overload -Removal of toxic agents
  21. 21. Applications of resealed erythrocytes Delivery of antiviral agents Oxygen deficiency therapy Microinjection of macromolecules Novel systems Nanoerythrosomes Erythrosomes
  22. 22. References Jain.S., Jain.N.K., resealed erythrocytes as drug carriers, Edited Jain N.K., Controlled And Novel Drug Delivery, New Delhi, CBS publishers, New Delhi, 2004, 256-281. Vyas S.P., Khar R.K., Targeted And Controlled Drug Delivery: Novel Carrier Systems, New Delhi, CBS publisher, 2004, 387-413.

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