Nano particles and released erythrocytes
Published on: Mar 3, 2016
Transcripts - Nano particles and released erythrocytes
Dr.Mrs. Yasmin Begum
Methods of preparation
Novel Nanoparticulate systems
Pharmaceutical aspects of Nanoparticles
Characterization of nanoparticles
In Vivo fate & Bio distribution of
Evaluation of nano particles
Nano derives from the greek word “nanos”
which means Dwarf or Extremely small. It
can be used as a prefix for any unit to mean
a billionth of that unit.
A nanometer is a billionth of a meter.
Nanoparticles are solid colloidal particles
ranging from 1to100nm in size.
They consist of micromolecular
materials in which the active ingredients
(drug or biologically active material) is
dissolved, entrapped, or encapsulated, or
absorbed, or attached.
The basic Concept involved is :
Selective and Effective Localization of
pharmacologically active moiety at preselected
target(s) in therapeutic concentration,,
Provided restriction of it’s access to non-target
normal tissues and cells.
Nanoparticles are mainly taken by :
ReticuloEndothelial System (RES), After the
Hence are useful to carry drugs to the liver and to
cells that are phagocytically active.
By modifying the surface characteristics of the
nanoparticles it is possible to enhance the delivery
of drugs to spleen relative to the liver.
Distribution of the nanoparticles in the body may
be achieved possibly by :
Coating of nanoparticles with certain Serum
components, Attachment of antibodies or sulfoxide
groups and the use of Magnetic nanoparticles.
It should be biochemically inert , non toxic
It should be stable both physically and
chemically in Invivo & invitro conditions.
Restrict drug distribution to non-target cells
or tissues or organs & should have uniform
Controllable & Predicate rate of drug
Drug release should not effect drug action
Specific Therapeutic amount of drug release
must be possessed
Carriers used must be biodegradable or readily
eliminated from the body without any problem
and no carrier induced modulation in disease
The preparation of the delivery system should
be easy or reasonable
simple, reproducible & cost effective.
Based On Method Of Preparation:
Nanocapsules are systems in which
the drug is confined to a cavity surrounded by a
unique polymer membrane.
Nanospheres are matrix systems in
which the drug is physically and uniformly dispersed.
Solid Lipid Nanoparticles
Copolymerized Peptide Nanoparticles
Nanocrystals and Nanosuspensions
Nanotubes And Nanowires
Solid lipid Nanoparticles:
New type of colloidal drug carrier system for i.v.
Consists of spherical solid lipid particles in the nm range,
dispersed in water or in aqueous surfactant solution.
Polymeric nanoparticles (PNPs) :
They are defined as particulate dispersions or solid particles
with size in the range of 10-1000nm.Composed of synthetic
or semi-synthetic Polymers.
Biodegradable polymeric nanoparticles Polylactic acid (PLA),
polyglycolic acid (PGA), Polylactic - glycolic acid (PLGA),
and Polymethyl methacrylate (PMMA) Phospholipids
These are the nanoparticles made up of inorganic (ceramic)
compounds silica, ( Inorganic/metal) titania and alumina.
Exist in size less than 50 nm,which helps them in evading
deeper parts of the body.
Polymeric system involving the self-assembly and self
aggregation of natural polymer amphiphiles cholesteroyl
pullulan , cholesteroyl dextran and agarose cholesterol
groups provide cross linking points.
Copolymerized Peptide Nanoparticles:
Drug moiety is covalently bound to the carrier instead of
being physically entrapped.
Nanocrystals And Nanosuspensions:
Pure drug coated with surfactant, Aggregation of these
particles in crystalline form .Drug powder dispersed in
aqueous surfactant solution.
Biological materials like proteins, enzymes, peptides etc…
are being utilized as a carriers for the drug delivery.
Nano particle can be administered by
parenteral, oral, nasal, occular routes.
By attaching specific ligands on to their
surfaces,nano particles can be used for directing
the drugs to specific target cells.
Improves stability and therapeutics index and
reduce toxic affects.
Both active & passive drug targetting can be
achieved by manipulating the particel size and
surface characteristics of nano particles
Small size & large surface area can lead to
particle aggregation .
Physical handling of nano particles is difficult
in liquid and dry forms.
Limited drug loading.
Toxic metabolites may form
PRE-POLYMERIZED POLYMERIZED IN PROCESS
Poly (E caprolactone)(PECL) Poly Isobutyl cyano acrylates
PLA(Poly lactic acid) PBCA(poly butyl cyano acrylates)
Poly lactide co glycolide (PLGA) PHCA(poly hexyl cyano acrylates)
Polystyrene Poly methyl methacyrlate (PMMA)
Nanoparticles can be prepared from
amphiphilic macromolecules, proteins &
The technique of their preparation involves
firstly, the aggregation of amphiphiles
followed by further stabilization either by
Heat denaturation or Chemical cross linking.
These process may occur in biphasic O/W or
W/O type dispersed system.
The cross linking method is exhaustively used
for the nano-encapsulation of drug.
The method involves the emulsification of
Bovine serum albumin(BSA)/ human serum
albumin(HAS) or protein aqueous solution in
oil using high pressure homogenization or
high frequency sonication.
The high temperature used in the original
method restrict the application of method to
heat sensitive drugs.
As an alternative to heat stabilization
method a chemical cross linking agent,
usually glutaraldehyde, is incorporated in to
Though the heat borne drawbacks are
obviated, yet a need to remove residual
cross-linking agent makes the method
Chemical dehydration has been reported for
producing BSA nanoparticles
Bhargava and Aindo suggested a simple chemical
cross-linking method in 1992
Hydroxypropyl cellulose solution in chloroform
was used as a continuous phase.
2,2,dimethylpropane(dehydrating agent) was
used to translate internal aqueous phase in to a
solid particulate dispersion.
This method produce nanoparticles of size
Polymers used for nanosphere preparation
Two different approaches are generally
adopted for the preparation of nanospheres
using in-situ polymerization technique:
Methods in which the monomer to be
polymerized is emulsified in a non-solvent
Methods in which the monomer is dissolved
in a solvent that is non solvent for the
resulting polymer (Dispersion polymerisation)
The process of emulsion polymerization can
be conventional or inverse, depending upon
the nature of the continuous phase in the
Two different mechanism:
Micellar nucleation and polymerization
Homogeneous nucleation and polymerization.
It involves the swollen
monomers micelles as
the site of nucleation
The monomers is
emulsified in non
solvent phase with the
help of surfactant
It leads to formation of
micelles and stabilized
It is applied in the case
where the monomer is
sufficiently soluble in the
continuous outer phase
The nucleation and
polymerization stages can
directly occur in this
phase, leading to the
formation of primary
chains called oligomer
When the oligomer have
reached a certain length
they precipitate and form
primary particles which
are stabilized by the
The polymerization rate is dependent on the
PH of the medium.
Anionic polymerization takes place in micelle
after diffusion of monomer molecules
through the water phase and is initiated by
negative charged compound
At neutral PH the rate of polymerization is
However at acidic ph i.e,2-4 the reaction
rate remains controlled and slow.
Eg:ethyl cynoacrylate- 2hr, hexyl
cynoacrylate-10 to 12hr.
In case of dispersion
instead of emulsified,is
dissolved in an aqueous
medium which acts as
the precipitant for
Nucleation is directly
induced in aqueous
monomer solution and
presence of stabilizer
or surfactant is not
necessary for the
formation of stable
The performed polymer
phase is transformed to
an embroynic sheath.
A polymer that
eventually become core
of nanoparticle and
drug molecule to be
loaded are dissolved in
a volatile solvent.
The solution is poured
in to a non-solvent for
both polymer and core
The polymer phase is
separated as a
coacervative phase at
The method is based on the process of
microencapsulation introduced by Lin & Sun
In case of nanoparticles preparation,aqueous
polyelectrolyte solution is carefully dissolved
in reverse micelles in an apolar bulk phase
with the help of an appropriate surfactant.
Subsequently, competing polyelectrolyte is
added to the bulk, which allows a layer of
insoluble polyelectrolyte complex to
coacervate at the interface.
Solvent extraction/ evaporation method
Salting out method
Solvent displacement method.
This method involves the
formation of a
emulsion between a
partially water miscible
solvent containing the
Ex: PLGA nanospheres
The polymer is solubilized
in a solvent (chloroform)
and dispersed in gelatin
solution by sonication to
yield emulsion O/W. the
solvent is eliminated by
used which breaks the
initial coarse emulsion in
The method involves the
incorporation of saturated
aqueous solution of (PVA)
into an acetone solution of
the polymer to form O/W
In this technique the
miscibility of both phases is
prevented by saturation of
external aqueous phase.
The precipitation of
polymer occurs when
sufficient amount of water
is added to external phase.
This method is based on the
interfacial deposition of a
displacement of a semi-polar
solvent miscible with water
from a lipophilic solution.
This method involves the use
of organic phase completely
soluble in aqueous phase
inducing immediate polymer
The solvent is eliminated and
the free flowing nanoparticles
can be obtained under reduced
Solid Lipid Nanoparticles:
These are sub-micron colloidal carriers (50-
100nm) which are composed of physiological
lipid dispersed in water or in a aqueous
Micro emulsion technique was used for the
production of solid lipid nanoparticles
Homogenization method at higher pressure
for either melted or solid lipids has been
suggested to obtain SLN.
Small size and relatively narrow size
distribution which provide biological
opportunities for site specific drug delivery
Controlled release of active drug over a long
period can be achieved
Protection of incorporated drug against
No toxic metabolites are produced
Relatively cheaper and stable.
Ease of industrial scale production by hot
Hot Homogenization Technique:
Homogenization of melted lipids at elevated
Cold Homogenization Technique:
Homogenization of a suspension of solid lipid
at room temperature.
Melting of lipid
Dissolution of the drug in the melted lipid
Mixing of the preheated dispersion medium
and the drug lipid melt
High pressure homogenization at a
temperature above the lipids melting point
Solidification of the nano emulsion by
cooling down to room temperature to form
Melting of the lipid
Dissolution of the drug in the melted lipid
Solidification of the drug loaded lipid in liquid
nitrogen or dry ice
Grinding in a powder mill(50-100 particles)
Dispersion of the lipid in the cold aqueous
Solid lipid nanoparticles.
Nanocrystals and Nanosuspensions are two
recently introduced aspects to drug delivery
The basic theme is to convert micronized
drug powders to drug nanoparticles.
Should be free from potential toxic impurities
Should be easy to store and administer
Should be sterile if parenteral use is advocated.
Three important process parameters are
performed before releasing them for clinical
o Freeze drying
This method has been
suggested for the
purification of nano
particles and the
method can be scaled
up from an industrial
In this method the
suspension os filtered
with direction of fluid
being tangential to
surface of membrane.
Depending on the type
of membrane used
either microfiltration or
ultra filtration can be
This technique involves the freezing of the
nanoparticle suspension and subsequent
sublimation of its water content under reduced
pressure to get freeflowing powder material
Prevention from degradation
Prevention from drug leakage, drug desorption.
Easy to handle and store and helps in long term
Readily dispersed in water without modifications
in their physicochemical properties.
Nanoparticles intended for parenteral use
should be sterilized to be pyrogen free.
Sterilization can achieved by:
Using aseptic technique throughout their
Subsequent sterilization treatments like
It is deduced from these consideration that
the sterilization of nanoparticles is a critical
step that should be systematically
investigated during formulation development
Intravenous injection of
colloidal carriers follow their
interactions with at least two
distinct groups of plasma
Phagocytosis of particulates
by elements of RES is
regulated by the presence
and balance b/w two groups
of serum components.
Opsonins that promote
Dysopsonins that supress the
Dysopsonins- IgA,SecretoryIgA .
Steric stabilized (stealth) nanoparticles
Magnetically guided nanoparticles(Fe3O4)
Biomimetic nanoparticles (biomimetic
Antibody coated nanoparticles.
Supercritical Fluid Technology
Structure and crystallinity
Specific surface area
Surface charge & electronic mobility
Drug entrapment efficiency
Photon correlation spectroscopy (PCS) : For
Laser diffractrometry : For larger particle.
Electron microscopy (EM) : Required coating of
conductive material such as gold & limited to
Transmission electron microscopy (TEM) :
Easier method & Permits differntiation among
nanocapsule & nanoparticle
Atomic force microscope
Laser force microscope Highresolution
Scanning electron microscope microscope
Helium or air using a gas pycnometer
Density gradiant centrifugation
3. Molecular weight :
Gel permeation chromatography using refractive
4. Structure & Crystallinity :
Thermoanalytical method such as,
1) Differential scanning calorimetry
2) Differential thermal analysis
5. Surface charge & electronic mobility :
Surface charge of particle can be determined by
measuring particle velocity in electrical field.
Laser Doppler Anemometry tech. for determination of
Surface charge is also measured as electrical mobility.
Charged composition critically decides bio-distribution
of nanoparticle .
Zeta potential can also be obtain by measuring by the
6.Surface Hydrophobicity :
Important influence on intraction of nanoparticles with
Several methods have been used,
1. Hydrophobic interaction chromatography.
2. Two phase partition.
3. contact angle measurement.
7. Invitro release :
Recently introduce modified Ultra-filtration tech.
Media used : phosphate buffer
8.Nano particle yield:
9.Drug entrapment efficiency:
Company Technology API Route of
Novavax, USA Micellar
BioSante, USA Calcium
(Merck & Co. Inc) (Wyeth-Ayerst Laboratories)
(American Biosciences, Inc.)
(Proctor and Gamble)
Nanoparticles are one of the
novel drug delivery systems, which can be of
potential use in controlling and targeting drug
delivery as well as in cosmetics textiles and
paints. Judging by the current interest and
previous successes, nanoparticulate drug
delivery systems seems to be a viable and
promising strategy for the biopharmaceutical
Vyas S.P. , Khar R.K. Targeted & Controlled Drug
Delivery, Novel Carrier Systems, CBS Publication
,2002 ,Page No.249-277,331-387.
Nanoparticles –A Review by VJ Mohanraj & Chen
Y, Tropical Journal of Pharmaceutical Research
2006; 5(1): 561-573
Jain N. K., Controlled and novel Drug Delivery,
1st edition 2001, CBS Publication; 292 - 301.
Source of erythrocytes
Isolation of erythrocytes
Drug loading in erythrocytes
Factors effecting resealed erythrocytes
Advantages of erythrocytes
Method of drug loading
In vitro characterization of erythrocytes
Present pharmaceutical scenario is aimed at
development of drug delivery systems which maximize
the drug targeting along with high therapeutic benefits
for safe and effective management of diseases.
Target drug delivery system indeed a very attractive
goal because in this system targeting of an active bio
molecule from effective drug delivery where
pharmacological agents directed specifically to its
Various cellular carriers has been used for drug
targeting among which cellular carriers(leukocytes,
platelets and erythrocytes) offer a great potential.
Erythrocytes also known as red
blood cells and have extensively
studied for their potential carrier
capabilities for delivery of drugs .
Diameter - 7-10μ
Life span - 120days
No. of cells/L of blood -
Shape, nucleus type -
biconcave disc like, anucleate
Cytoplasm - pink(Hb),halo in
Functions - transports Hb that
binds to O2 &CO2
Although qualitatively similar to that of plasma
.however, quantitatively it differs from that of plasma.
The concentration of K+ is more in erythrocytes and
Na+ in plasma.
The osmotic pressure of the interior of the erythrocytes
is equal to that of the plasma and termed as isotonic
(0.9% NaCl or normal physiological saline.)
Changes in the osmotic pressure of the medium
surrounding the red blood cells changes the
morphology of the cells.
If the medium is Hypotonic, water diffuses into
the cells and they get swelled and eventually
loose all their hemoglobin content and may
If the medium is Hypertonic,(i.e. higher
osmotic pressure than 0.9% NaCl) they will
shrink and become irregular in shape.
Balanced ion solutions like Ringer’s and
Tyrode’s soln. which are not only isotonic
but also contains ions in proper quantity are
used in erythrocyte related experiments.
If blood is placed into a tube and
centrifuged, the cells and the plasma
The erythrocytes, which are heavy, will
settle down to the bottom of the tube,
while the plasma rises up to the top and
the leukocytes and platelets will form a
thin layer (buffy coat) between the
erythrocytes and the plasma.
The haematocrit is defined as the
percentage of whole
blood made up of erythrocytes.
Different mammalian erythrocytes have been
used for drug loading, resealing and
subsequent use in drug and enzyme delivery.
E.g. mice, cattle, pigs, dogs, sheep, goats,
monkeys, chicken, rats, and rabbits etc.
EDTA or heparin can be used as anticoagulants
Blood is collected into heparinized tubes by venipuncture
Blood is withdrawn from cardiac/splenic puncture(in small
animal) and through veins (in large animals) in a syringe
containing a drop of anti coagulant.
The whole blood is centrifuged at 2500 rpm for 5 min at
4 ±1.0o C in a refrigerated centrifuge.
The serum coats are carefully removed and packed cells
washed three times with phosphate buffer saline (pH=7.4).
The washed erythrocytes are diluted with PBS and stored
at 40oC until used.
Use of red cell loader.
Isotonic osmotic lysis.
Chemical perturbation of the membrane.
Electro-insertion or electroencapsulation.
Entrapment by endocytosis.
Loading by lipid fusion.
Erythrocytes to undergo
reversible swelling in a
An increase in volume leads to
an initial change in the shape
from biconcave to spherical.
The cells can maintain their
integrity up to a tonicity of
150mosm/kg above which the
membrane ruptures, releasing
the cellular contents.
Membrane ruptured RBC Loaded RBC Resealed Loaded RBC
Chemicals – Urea, Polyethylene, Polypropylene, and
These ruptured erythrocytes as drug carriers is based on the
fact that the ruptured membranes can be resealed by restoring
Upon incubation at 25oc the cells resume their original
biconcave shape and recover original impermeability.
In this method, a volume of packed
erythrocytes is diluted with 2–20 volumes of
aqueous solution of a drug.
The solution tonicity is then restored by adding
a hypertonic buffer.
The resultant mixture is then centrifuged, the
supernatant is discarded, and the pellet is
washed with isotonic buffer solution.
Membrane ruptured RBC
Compounds that can be encapsulated are enzymes such as -
galactosidase and -glucosidase , asparginase,and arginase,
The technique is based upon initial controlled swelling
in a hypotonic buffered solution. This mixture is
centrifuged at low g values.
The supernatant is discarded and the cell fraction is
brought to the lysis point by adding 100–120 L portions
of an aqueous solution of the drug to be encapsulated.
The mixture is centrifuged between the drug-addition
The lysis point is detected by the disappearance of a
distinct boundary between the cell fraction and the
supernatant upon centrifugation.
The tonicity of a cell mixture is restored at the lysis
point by adding a calculated amount of hypotonic
Then, the cell suspension is incubated at 37 C to
reanneal the resealed erythrocytes
Loaded RBC Resealed Loaded RBC
5 min incubation
at 0 0c
Drugs: Propranolol, Asparginase, Methotrexate,
Insulin , Metronidazole , Levothyroxine, Isoniazid.
This method, also known as the osmotic pulse
method, involves isotonic hemolysis that is
achieved by physical or chemical means.
The isotonic solutions may or may not be
If erythrocytes are incubated in solutions of a
substance with high membrane permeability,
the solute will diffuse into the cells because of
the concentration gradient.
This process is followed by an influx of water
to maintain osmotic equilibrium.
rupturing Isotonic buffer
Isotonically ruptured RBC
Compounds encapsulated are – Urea,
polyethylene, polypropylene, and NH4Cl
Buffer containing ATP,
MgCl2, and CaCl2
At 250 C
Drugs: primaquine ,quinolines, vinblastine,
propranolol, vitamin A.
Fig:- Entrapment By Endocytosis Method
In the process, an isotonic, buffered suspension of
erythrocytes with a hematocrit value of 70–80 is prepared
and placed in a conventional dialysis tube immersed in 10–
20 volumes of a hypotonic buffer.
The medium is agitated slowly for 2 h.
The tonicity of the dialysis tube is restored by directly
adding a calculated amount of a hypotonic buffer to the
surrounding medium or by replacing the surrounding
medium by isotonic buffer.
The drug to be loaded can be added by dissolving the drug
in isotonic cell suspending buffer inside a dialysis bag at the
beginning of the experiment.
Placed in dialysis
bag with air bubble
Dialysis bag placed in 200ml of lysis
buffer with mechanical rotator 2hrs. 4c.
Dialysis bag placed in Resealing buffer
with mechanical rotator 30 min 37c.
DRUGS: gentamicin, pentamidine,
interlukin-2 , desferroxamine and recombinant
This method is based on the observation that electrical
shock brings about irreversible changes in an
The use of transient electrolysis to generate desirable
membrane permeability for drug loading.
The erythrocyte membrane is opened by a dielectric
Subsequently, the pores can be resealed by incubation
at 37OC in an isotonic medium.
2.2 Kv Current for
20 micro sec
At 250 C
3.7 Kv Current for
20 micro sec
DRUGS: Urease , Methotrexate ,
isoniazid , human glycophorin ,
DNA fragments, and latex particles of diameter
Electro-insertion or Electro-encapsulation
Fig:- Electro-encapsulation Method
It is a novel method for entrapment of nondiffusible drugs
They developed a piece of equipment called a “red cell
With as little as 50 mL of a blood sample, different
biologically active compounds were entrapped into
erythrocytes within a period of 2 h at room temperature
under blood banking conditions.
The process is based on two sequential hypotonic dilutions
of washed erythrocytes followed by concentration with a
hemofilter and an isotonic resealing of the cells.
There was 30% drug loading with 35–50% cell recovery.
The processed erythrocytes had normal survival in vivo.
The same cells could be used for targeting by improving
their recognition by tissue macrophages.
“THIS METHOD IS BASED ON THE FACT THAT THE PERMEABILITY
OF THE ERYTHROCYTES INCREASES ON EXPOSURE TO CERTAIN
CHEMICAL AGENTS .”
However, these methods induce irreversible destructive changes in the cell
membrane and hence are not very popular.
RBC with increased
Routes of administration include:
i. Intravenous (most common).
There are mainly three ways for a drug to efflux out
from erythrocyte carriers.
Diffusion through the membrane of the cell.
Using a specific transport system.
Resealed erythrocytes after loading are characterized for following
1. Drug Content:
Packed loaded erythrocytes are 1st deproteinized with acetonitrile and
subjected to centrifugation at 2500rpm for 10min. The clear
supernatant is analyzed for the drug content.
2. IN VITRO DRUG AND HAEMOGLOBIN
Normal and loaded erythrocytes are incubated at 37+ 20c in phosphate
buffer saline (pH-7.4) at 50% haematocrit in a metabolic rotating
wheel incubator bath.
Periodically,the samples are with drawn with the help of a hypodermic
syringe fitted with a 0.8 μ spectrophore membrane filter.
Percent haemoglobin can similarly calculated at various time
intervals at 540run spectrophotometrically.
Laser light scattering may also be used to evaluate haemoglobin
content of individual resealed erythrocytes.
It is reliable parameter for invitro evaluation of carrier erytrocytes
with respect to shelf life, invivo survival & effect of encapsulated
When RBC are exposed to solution of varying tonicities, this shape
changes due to osmotic balance.
To evaluate the effects of varying tonicities,drug loaded erythrocytes are
incubated with saline solutions of different tonicities at 37+20c for
The suspension after centrifugation for 15min, 2000rpm is assayed for
drug or haemoglobin release.
Osmotic shock describes a sudden exposure of drug loaded erytrocytes
to an environment, which is far from isotonic to evaluate the ability of
resealed erythrocytesto withstand the stress and maintain their integrity
as well as appearance.
Incubating the resealed erythrocytes with distilled water for 15min
followed by centrifugation at 3000rpm for 15min, may cause the release
of haemoglobin to varying degrees which could be estimated
This parameter indicates the effect of shear force and pressure by which
resealed erytrocytes formulations are injected, on integrity of the loaded
Loaded erythrocytes are passed through a 23-gaug hypodermic needle at
a flow rate of 10min. After every pass,aliquot of the suspension is
withdrawn and centrifuged at 300g for 15 min, and haemoglobin
content, leached out is estimated spectrophotometrically.
Phase contrast optical microscopy, transmission electron microscopy &
scanning electron microscopy are the microscopic methods used to
evaluate the shape, size & surface features of loaded erythrocytes.
Percent cell recovery can be determined by assessing the number of
intact erytrocytes remaining per cubic mm with the help of
Erythrocytes as drug/ enzyme carriers:
Erythrocytes as carriers for enzymes.
Erythrocytes as carriers for drugs.
Erythrocytes as carriers for proteins and macromolecules.
Drug targeting to RES organs Surface modification with antibodies.
Surface modification with Glutaraldehyde.
Surface modification involving sulphydryls.
Drug targeting to Liver:
Enzyme deficiency/replacement therapy
Treatment of liver tumors
Treatment of parasitic diseases
Removal of RES Iron Overload
An erythrocytes based new drug carrier, named
nanoerythrosome has been developed which is prepared by
extrusion of erythrocyte ghosts to produce small vesicles
having an average diameter of 100 nm.
Daunorubicin (DNR) was covalently conjugated to the
nEryt (nEryt-DNR) using glutaraldehyde as
homobifunctional linking arm. This led to a complex that is
more active than free DNR both in vitro and in vivo.
Daunorubicin (DNR) conjugated to these nanoerythrosomes
has a higher antineoplastic index than the free drug.
These are specially engineered vesicular systems
that are chemically cross-linked to human
erythrocytes’ support upon which a lipid bilayer is
This process is achieved by modifying a reverse-phase
These vesicles have been proposed as useful
encapsulation systems form macromolecular
The use of resealed erythrocytes looks promising for a
safe and sure delivery of various drugs for passive and
However, the concept needs further optimization to
become a routine drug delivery system.
The same concept also can be extended to the delivery
of biopharmaceuticals and much remains to be
explored regarding the potential of resealed
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