3-Erythrocytes as Drug Carriers
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Transcript of 3-Erythrocytes as Drug Carriers
Presented by. Atif Ali
ErythrocytesAs Drug Carriers
Presentation by
Atif Ali
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
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
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
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
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
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.
Membrane perturbation method
RBCAmphotericin B
e.g. Chemical agents
Increased permeability of RBC
Resealing Buffer
Drug
Resealed RBC
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
Entrapment By Endocytosis:-
RBCDrug
Suspension+
Buffer containing ATP, MgCl2, and CaCl2
At 250 CLoaded RBC
Resealing Buffer
Resealed RBC
Fig;- Entrapment By Endocytos Method
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
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
In vitro characterization
In vitro characterization
• Mechanism of release of resealed erythrocytes
• Shelf & storage stability of resealed erythrocytes
Some Important Aspects Of Resealed Erythrocytes
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
Applications of resealed erythrocytes
Delivery of antiviral agentsOxygen deficiency therapy