Effective permeation and retention effect [epr effect

FULL DETAIL ABOUT EPR EFFECT

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 1 INTRODUCTION 3 2 DEFINITION OF EPR EFFECT 4-5 3 TUMOR VASCULATURE CONTRIBUTING TO EPR EFFECT 6-9 4 APPORACH TO POTENTIATE THE EPR EFFECT 10 4A 4B TARGETTING TUMOR VASCULATURE OR STROMA REDUCING TUMOR CELL BARRIER TO DRUG DELIVERY 11-14 15-16 5 CURRENT STATUS OF EPR. 17 6 PROSPECT OF EPR EFFECT. 18

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 . P roduce 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 As we known factors initiate tumor permeability Bradykinin, prostaglandins, vascular endothelial growth factor (VEGF) not generated in normal circumstances. There are two approaches by which EPR effect can be potentiated. Targeting tumor vasculature or stroma . 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 deliver y .

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 .

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