3-Erythrocytes as Drug Carriers
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Presented by. Atif Ali
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ErythrocytesAs Drug Carriers
Presentation by
Atif Ali
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Content • Introduction • Erythrocytes as drug carriers • Basic concept of erythrocytes• Advantages & limitations• Source & Isolation of Erythrocytes• Methods of drug Loading • Characterization• Drug release, Storage • Applications• Conclusion
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ErythrocytesProperties as carrier :- Appropriate size, shape. 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
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Erythrocytes • Erythro= red• Cytes = cells
• Biconcave discs, anucleate.• Filled with hemoglobin
(Hb), a protein that functions in oxgen transport
• Contain the plasma membrane protein and other proteins that:– Give erythrocytes their
flexibility– Allow them to change shape
as necessary
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Erythrocytes
Healthy adult male= 5.4 millions cells/mm 3Healthy adult female= 4.8 millions cells/mm 3
Matured RBCs have no nucleus Ribosome & Mitochondria . Therefore all space is available for drug carrier.
Reticulocytes- immature erythrocytes
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Advantages of erythrocyte as carrier:-Biodegradable Isolation is easy Non immunogenic
large volume of drug can be encapsulated in small volume of erythrocytesProlong systemic activity of drug
• Protection from premature degration• Reduce Adverse Effect• Peptide & Enzyme Delivery
limitations :-Possibility of Leakage of cells & dose dumping
Molecule Alter Physiology Of cell
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Source, fractionation & isolation of erythrocytes
Source:- mice, cattle, pig, dog, sheep, goat, monkey, chicken, rat, rabbit & human
Whole blood can be collected by venipuncture in heparinized tube
Red blood cells can be harvested & centrifuged
Different centrifugal force & different buffer composition for different species is used
Fresh blood is used for loading of drugs.
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Membrane perturbation method
RBCAmphotericin B
e.g. Chemical agents
Increased permeability of RBC
Resealing Buffer
Drug
Resealed RBC
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Electro-insertion or Electro-encapsulation
RBC 2.2 Kv Current for 20 micro sec
At 250 CPulsation medium
+ +Drug
Loading suspension
3.7 Kv Current for 20 micro sec
Isotonic NaClLoaded RBC
Resealing Buffer
Resealed RBC
Fig:- Electro-encapsulation Method
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Entrapment By Endocytosis:-
RBCDrug
Suspension+
Buffer containing ATP, MgCl2, and CaCl2
At 250 CLoaded RBC
Resealing Buffer
Resealed RBC
Fig;- Entrapment By Endocytos Method
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Hypotonic Dilution
RBC Membrane ruptured RBC Loaded RBC
Resealed Loaded RBC
0.4% NaCl
Hypotonic
Drug
Loading buffer
Resealing buffer
Incubation at 250c
Efficiency 1-8% Enzymes delivery
Hypotonic med
Isotonic med.
Washed
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Hypotonic Preswelling
RBC 0.6%w/v NaCl Swelled
RBC Drug + Loading buffer
5 min incubation at 0 0c
Loaded
RBC
Incubation at 25 0c
Resealing Buffer
Resealed
RBC
Efficiency 72%
Fi:- Preswell Method
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In vitro characterization
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In vitro characterization
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• Mechanism of release of resealed erythrocytes
• Shelf & storage stability of resealed erythrocytes
Some Important Aspects Of Resealed Erythrocytes
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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
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Applications of resealed erythrocytes
Delivery of antiviral agentsOxygen deficiency therapy
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