The EPR effect allows macromolecular drugs to selectively accumulate and be retained in solid tumors over normal tissues. It exploits the anatomical and physiological differences between tumor and normal vasculature. Tumor blood vessels are defective and permeable, lacking smooth muscle and pericytes. They also have poor lymphatic drainage. This allows nanoparticles and macromolecules to extravasate into tumors and be retained, achieving drug concentrations 10-200 times higher than in normal tissues. Various approaches can potentiate the EPR effect, such as targeting tumor vasculature to increase permeability or reducing tumor cell barriers to enhance penetration and retention of drug delivery systems.

1. EFFECTIVE
PERMEATION AND
RETENTION EFFECT
[EPR EFFECT]
BY NEERAJ PANDEY
M PHARM 1st YEAR
RITM LUCKNOW

2. S.NO TABLE OF CONTENT PAGE NO
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4-5
6-9
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11-14
15-16
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3. INTRODUCTION
 Treatment of solid tumor based on anatomical and
physiological difference from normal tissue.
 Macromolecular drug could accumulate and retain
in solid tumor selectively and they will not
distribute in normal tissue.
 EPR based chemotherapy to improve delivery of
drug to tumors.
 Also useful for cancer diagnosis and therapy.

4. DEFINITION OF EPR
EFFECT
 EPR based tumor targeting developed by using
polymer modification , micelle , liposome.
 It exhibited 10-200 times higher concentration in
tumor than in normal tissue (Heart kidney skin
muscle).
 Act on anatomical and physiological character of
solid tumor.
 Angiogenesis and vascular density.

5.  Tumor have blood vessel with defective architecture.

6. TUMOR VASCULATURE
CONTRIBUTING TO EPR
EFFECT
PERMEABILITY
 Newly formed blood vessels have defective architecture.
 Produce vascular permeability.
 Bradykinin , prostaglandins , vascular endothelial growth
factor (VEGF).
 Vascular permeability to supply nitrogen and oxygen.

7. PERMEABILITY
TUMOR CELL SHOWING
INCREASED PERMEABILITY
IN COMPARISION OF
NORMAL BLOOD VESSELS

8. RETENTION
Tumor tissue exhibit poor lymphatic drainage.
Small molecule does not show EPR effect because
they can easily pass to the tumor tissue and to the
normal cell and diffuse back into blood capillaries or
in lymphatic system.

9. IMAGE SHOWING RETENTION
IN BLOOD VESSELS DUE TO
MISCELLE FORMATION AND
POOR DRAINAGE
IMAGE

10. APPROACHES TO
POTENTIATE EPR EFFECT
o As we known factors initiate tumor permeability
Bradykinin, prostaglandins, vascular endothelial
growth factor (VEGF) not generated in normal
circumstances.
o There are two approaches by which EPR effect can
be potentiated.
A. Targeting tumor vasculature or stroma .
B. Reducing tumor cell barrier to drug delivery.

11. TARGETTING TUMOR CELL VASCULATURE
OR STROMA
A-INCREASED DELIVERY OF NANOPARTICLES TO TUMOR UNDER AG-||
 Tumor blood vessels lack pericytes or smooth muscle need
for vasoconstriction.
 On infusion of angiotensin-|| it shows very less
vasoconstriction.
 Inducing hypertensive state of angiotensin-|| tumor blood
vessel will open.
 Result increased blood flow and increased drug delivery.

12. USE OF AG-
||(HYPERTENSION)
INCREASED HYPERTENSION AND AG-||
OPEN PORES

13. B- USE OF NITROGLYCERIN FOR
ENHANCED DELIVERY TO TUMORS
 There is no major facilitator of EPR effect.
 Its permeability increased by using NO or NO
releasing compound nitroglycerin.
 Facilitate EPR effect via NO generation in tumors.
 It enhance drug delivery up to 2to3 folds.
 Result improved therapeutic effect.
 Bacteria lactobacillus casei (iv) 10 folds.

14. C- USE ACE INHIBITORS
 ACE(Angiotensin converting enzyme) Inhibit
degradation of Bradykinin .
 Raising local level of bradykinin concentration in
tumor tissue in body.
 Increased deformation in tissue increased
permeability.

15. 2-REDUCING TUMOR CELL
BARIER TO DRUG DELIVERY
 Tumor cells themselves act as a barrier to deeper
penetration of nanoparticles.
 Short term application of radiation , photodynamic
therapy and chemical therapeutics agents to kill
cancer cells.
 This can give for long periods several weeks
sustained drug delivery with marked therapeutic
effect.

16. EXAMPLE REMOVING
BARRIER TO DRUG DELIVERY

17. CURRENT STATUS OF
TARGETTED DRUG DELIVERY
TO TUMORS
 Conventional approaches to treat cancer are
chemotherapy , radiation , surgical intervention
confined to removal of early stage and small tumor
removal.
 Tumor targeted drug delivery system has received great
attention due to increased anticipation of it using
nanotechnology.
 It overcome difficulties associated with conventional
drug delivery-rapid clearance aqueous insolubility lack
of selectivity result non toxic effect in normal cell
reducing dose in tumor cell.

18. PROSPECT OF EPR EFFECT
 Many current tumor drug delivery system are
trying to go further than just providing tumor
accumulation.
 Attempts are under way to combine tumor cell
specific targeting with longevity sponsored EPR
based accumulation.
 EPR effect can be facilitated by various means.

19. THANK
YOU