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Erythrosomes: Pinank V. Pandya Babaria Institute of Pharmacy, Vadodara

Erythrosomes are specially engineered vesicular systems composed of a lipid bilayer coated onto chemically cross-linked human erythrocyte cytoskeletons. They can encapsulate macromolecular drugs and are proposed as a useful drug delivery system. Erythrosomes are prepared through a modified reverse phase evaporation method and have desirable properties like biodegradability, ability to circulate and encapsulate large drug volumes, and biocompatibility. They show potential for targeted drug delivery to organs within the reticuloendothelial system and may help treat diseases like cancer through genetic engineering approaches coupled with drug delivery.

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Sagar Patel
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520 views21 pages

Erythrosomes: Pinank V. Pandya Babaria Institute of Pharmacy, Vadodara

Erythrosomes are specially engineered vesicular systems composed of a lipid bilayer coated onto chemically cross-linked human erythrocyte cytoskeletons. They can encapsulate macromolecular drugs and are proposed as a useful drug delivery system. Erythrosomes are prepared through a modified reverse phase evaporation method and have desirable properties like biodegradability, ability to circulate and encapsulate large drug volumes, and biocompatibility. They show potential for targeted drug delivery to organs within the reticuloendothelial system and may help treat diseases like cancer through genetic engineering approaches coupled with drug delivery.

Uploaded by

Sagar Patel
Copyright
© Attribution Non-Commercial (BY-NC)
We take content rights seriously. If you suspect this is your content, claim it here.
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ERYTHROSOMES

Pinank V. Pandya
BABARIA INSTITUTE OF PHARMACY, VADODARA
INTRODUCTION
 What are erythrosomes?
• They are specially engineered vesicular systems
in which chemically cross-linked human
erythrocyte cytoskeleton are as a support on
which a lipid bilayer is coated.
• This can be achieved by modified procedure
normally adopted for reverse phase evaporation.
• They are proposed as useful encapsulation
system particularly for macromolecular drugs.
HISTORY
• Erythrocytes (RBCs) were discovered in 1658.
• The carrier potential of these cells was first
realized in early 1970s.
They are difficult to engineer for a non RES target,
but recent innovation based on biophysically
devices may render them suitable for targeting
to organs other than RES. (Juliano,1980;
DeLoach et al, 1991; Vyas & Jain, 1994)
Why erythrosome?
 The desirable properties, which substantiate
stability of RBCs as drug carrier are:-
• Biodegradability
• Circulate through circulatory system.
• Large volume of material can be encapsulated.
• can be utilized for organ targeting with in RES.
• A wide variety of bioactive agents can be
encapsulated within them.
• Biocompatibility.
METHOD OF PREPARATION
 ISOLATION OF ERYTHROCYTES :
-SOURCE :- Different mammalian RBCs have been
exploited for drug loading. Majority of them
constructed for RBCs of mice, cattle, pigs, dogs,
sheep, goats, monkeys, chicken, rats & rabbits.
-ISOLATION:- Blood is collected in heparinized
tubes by vein puncture (EDTA or heparin can be
used as anti coagulant). Fresh RBCs are preffered
because of their higher encapsulation efficiency.
• RBCs are harvested & washed by centrifugation. According
to source centrifugal force & washing fluid is changed.
-General conditions:-
• Centrifugation-2000 RPM for 5 min at 4*C
• Buffer solution(washing fluid):
• NaCl -14 mmol/L
• KCl -16 mmol
• MgCl2 -4 mmol
• CaCl2 -2 mmol
Tris -5 mmol
RBC s are often stored in acid-citrate-dextrose
buffer at 4*C upto 48h prior to use.
 METHOD OF DRUG LOADING :
Mostly hypotonic lysis of cell in a solution
containing drug/enzyme to be entrapped followed
by restoration of tonicity to reseal them serves as a
loading procedure.
other techniques such as electrical breakdown,
endocytosis, chemical purturbation of membrane &
lipid erythrocyte fusion have also been utilised.
SHELF & STORAGE STABILITY OF
ERYTHROSOMES

 It is a major challenge in the their practical utility


as DDS.
• Lewis & alpar, 1984 have reported that
encapsulated product & carrier both exhibit
satisfactory shelf stability, when stored in Hank’s
balanced salt solution (HBBS)at 4*C for 2 weeks.
• Similar results were obtained by suspending cells
in oxygenated HBBS containing 1% soft bloom
gelatin.
• The cells are well recovered after liquefying the
gel by placing the tube in water bath at 37*C
followed by centrifugation.
• Under clinical condition standard blood bags may
be used for both encapsulation & storage.
• The procedure would be to used group
‘O’(universal donor) cells by preswell or dialysis
technique.
• Another method utilized for storage has been the
cryopreservation of RBCs in liquid nitrogen.
IN VIVO SURVIVAL AND
IMMUNOLOGICAL
CONSEQUENCES
• A bimodel type of survival kinetic is observed :
A rapid loss of cell during first 24 h followed
much slower release after word.
• The early loss that accounts for 15% of total
population represents the cells that are severly
damaged during drug loading.
• The inter subject & inter species variation from
different sources require ajudicial analysis &use
of the source before experiment is designed.
• There three general modes of efflux of loaded
drug from erythrosome.
-phagocytosis
-diffusion
-specific transport mechanism
• The phagocytosis occurs within RES.
• The degree of cross linking determines
whether spleen or liver will preferentially
remove the cell.
• It is observed that erythrocyte carriers
constructed from analogous sources do not
elicit an immunological consequences.
BIOMEDICAL APPLICATIONS OF ERYTHROSOMES
(1) Erythrosomes as carriers of enzymes:-
-ideal carriers of enzymes in inherited metabolic
diseases.
-enzymes that are usually carried are
catalase , urease , uricase , invertase, arginase ,
asparaginase , glucuronidase , galactosidase etc.
e.g. alcohol dehydrogenase & acetaldehyde
dehydrogenase encapsulated in human RBCs used
in vivo for complete metabolism of ethanol.
(2) Erythrosomes as carrier of drugs
-slow and sustained release of drugs in
treatment of paracytic disease.
-erythrosomes serves as ideal carrier for
antineoplastic agents like bleomycin,
actinomycin-D, adriamycin or cytosin
arabinoside.
-vitamins & steroids have also been
encapsulated in erythrosomes.
(3) As carriers of proteins & macromolecules
-Bird et al.1983 proposed erythrocytes as
carrier for insulin for its sustain release.
-erythrosomes may serve as cellular sustain
delivery system for in vivo administration
of recombinant human erythropoeitin.
-RBCs coated with recombinant interlukin-2
(rIL-2) are reported to provide sustain
delivery so as to allow low and non toxic
concentrations of IL-2 in circulation.
(4) Drug targeting
-osmotically loaded ehrocytes can act as
drug carrier in systemic circulation.
-chemically surface modified erythrocytes
are targeted to organ of the mononuclear
phagocytic system /reticular endothelial
system because changes incorporated in
membrane that are recognized by
macrophage cell.
 Treatment of paracytic disease
-paracytic disease in which paracyte reside
in RES have been effectively treated with
erythrosomes.
-Pentamidine primaquine phosphate &
metronidazole have been successfully
utilized for treatment of leishmaniasis,
malaria, extra intestinal amoebiasis on
exp. Laboratory models.
• Targeting in areas other than RES using:
-paramagnetic particle loaded RBCs.
-photosensitive element loaded RBCs.
-ultra sound waves.
-target specific immunoglobulin attached to
RBCs.
(5)In oxygen deficiency therapy
 erythrocytes are used in case of oxygen
deficiency where an improved oxygen
supply is required as in following cases:
-high altitude condition (where oxygen partial pressure is low)
-small number of alveoli
-increased resistance to oxygen diffusion in lungs
-increased radio sensitivity in of radiation sensitive tumors
-liver mediated detoxification process where an increased oxygen supply is
required.
- Inositol hexaphosphate (IHP, phytic acid)
loaded in RBCs binds irreversibly to hemoglobin
& reduces its oxygen binding, thus releasing
same in capillaries.
(6) Erythrosomes in cell biological application
 microinjection of macromolecules into cultured
cells using erythrocyte ghosts :
-using either Sendai virus (haemagglutinating
virus of
Japan, HVJ) or PEG mediated fusion, & then
macromolecules are transferred efficiently from
cytoplasm to nucleus of their expression.
-erythrocyte ghost cell fusion (microinjection)
method mediated HVJ is relatively easier, & can
be used for microinjection in many cells at the
same time.
(7) Cell biological application
-fragment A of diphtheria toxin (which on
entering cytoplasm inhibits peptide chain
elongation in translation &causing cell
death) can be introduced in to target cell
by erythrocyte ghost cell fusion.
FUTURE PERSPECTIVE
• A large amount of valuable work is needed
so as to utilize the potential of erythrocytes
in passive as well as active targeting of
drugs.
• Diseases like cancer can surely find its
cure
• Genetic engineering aspects can be
coupled to give newer dimension to the
existing drug cellular concept.

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