Dosage form design

1. Immunoglobulins As
Drug delivery system
Under supervision of
Dr Nada
Drug
Carrier
Targeting agent (IG)

2. Contents
• What Are immunoglobulins
• Functions of IGs
• Advantages of using IGs as DDS
• Applications

3. What Are immunoglobulins

4. Functions of IGs
Agglutination
of bacteria
Neutralization
of toxins and
viruses
Prevention of
m.o.
attachment
Complement
activation

5. Functions of IGs
New function
Its Use as
Drug
delivery
system
Targeting
technique

6. Advantages
Targeted DDS
Lower dose with
lower side
effects
Better efficiency
of drug
Better
penetration of
poor accessible
tissue

7. Applications
• PEG-immunoliposome
• ATTEMPTS
• Polmerizable antibody fab fragment
• Immunoconjugates
• ADEPT

8. PEG-Liposomes
• Immunoliposomes using
an antibody as a
targeting ligand and a
lipid vesicle as a carrier
for both hydrophobic
and hydrophilic
drugs
• https://www.youtube.com/watch?v=gRx3BB0KCHg

9. PEG-liposomes
Studies in vivo revealed
1)bound antibodies lead to
enhanced uptake of the
immunoliposomes by the
reticuloendothelial system
2)the targeting efficiency
depends on the antibody
density on the surface
Adding linkers like
either monosialoganglioside
or polyethylene glycol
derivatives of
phosphatidylethanolamine
are not readily taken up by
the macrophages in the RES
Prolonging the half life
the free PEG chains
effectively block the RES
uptake of the liposomes,
resulting in elevated blood
concentration of the
liposomes

10. ATTEMPTS
Antibody targeted
triggered
electrically
modified prodrug
type strategy
Introduces both of
the targeting and
prodrug features
onto the protein
drugs
Consisting of
antibodies linked
with
heparin(linker), and
The cell penetrating
peptide (CPP)
modified drug
component.

11. Synthesis

12. ATTEMPTS
charge to
charge
interaction
Anionic heparin
on the targeting
components
Cationic CPP on
the modified
drug component
(Prodrug)

13. HOW WILL THE DRUG DISSOCIATE
FROM THE HEPARIN-IG COMPLEX ??
Major question !!!??

14. ATTEMPTS
As the
protamine held
higher heparin-
binding affinity
than CPP
Why so ???
Heparin antidote
protamine
sulfate is
systemically
injected as a
triggering agent
to dissociate the
CPP-Drug part
from its Target-
Heparin
secondly
Following i.v.
administration,
the antibody-
guided
complexes
would be
accumulated at
the tumor site
while sparing
interaction with
normal tissue
through
antibody
targeting
Firstly

15. Polmerizable antibody fab fragment
• Preparation of polmerizable antibody fab fragment targeted polymeric
drug delivery system.

16. Ex of anticancer drug
Photodynamic
anticancer
with PEG spacer
(MA-PEG-Fab)
possessed a higher
reactivity.
Fab fragment (MA-
fab) which
recognizes OA-3
antigen expressed
on most human
ovarian carcinoma

17. Immunoconjugates
• One of the engineered forms of
immunoconjugates is covalently
bound by a synthetic linker to a
cytotoxic drug, plant or bacterial
toxin, enzyme, radio—nuclitide .
• Anti-body domain to selectively
localize the actual therapeutic
moiety to the antigen present on
tumor cells or on cells of the
tumor neovasculature.

18. Cont.
• Antibody-drug conjugates
consist of three components:
antibody, linker, and cytotoxin.
• Antibody targeted to a tumor-
associated antigen acts as a
carrier for drug delivery and
can be conjugated by
cleavable or uncleavable
linkers.
• The idea of conjugating
antibodies to a radioactive
tracer or a cytotoxic agent for
diagnostic and therapeutic
purposes.
Target
Selection
No single molecule
has been found to be
present exclusively on
cancer cells.
Several antigens have
been demonstrated to
be more expressed on
tumor than a normal
cells, making them
suitable, though not
yet idea.

19. Importance of Antibody Affinity Modulation to
Optimize Therapeutic Effect: .
Intuitively defined as the strength of the interaction between antigen and
antibody.
Affinities are more desirable for diagnostic or theraputic applications, In this
natural process, point mutation models antibody surfaces generating an
improved interaction with the target.
Affinity can be increased by structure-based site-directed mutagenesis in
vitro.
Mutations have proved important to provide large increase in affinity,
stability, and expression, and selection can lead to isolation of antibodies
with enhanced affinity.

20. ADEPT
• Antibody-directed enzyme prodrug therapy
The prodrug
administered, the
bound enzyme
transforms the
nontoxic compound in
its active form, which
kills tumor site
efficiently.
The remaining
unbound conjugates
are eliminated from
the blood stream.
Antibody-enzyme
conjugates are
administered to reach
the cells and
expressing the
selected target.
Uses enzymes
selectively driven to
their target to activate
prodrugs.