Cellular uptake of drugs can occur through passive diffusion of small molecules or active transport of larger particles via endocytosis, exocytosis, phagocytosis, or pinocytosis. Transport across epithelial barriers relies on passive diffusion, carriers, or endocytosis. Extravasation from blood vessels depends on permeability and physicochemical drug properties, while lymphatic uptake drains drug molecules from tissues. The reticuloendothelial system phagocytoses pathogens and debris from circulation and tissues.

2. CONTENT
▪ Cellular uptake & processing
▪ Transport across epithelial barrier
▪ Extravasation
▪ Lymphatic uptake
▪ Function of RES
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3. CELLULAR UPTAKE AND PROCESSING
▪ Following administration , a drug frequently passes through various
cell membranes and reach its target site.
▪ Low molecular weight drugs enter or pass through cells by simple
diffusion.
▪ TDDS comprising of macromolecules are unable to enter the cells by
simple processes.
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4. ▪ However, large particles are able to enter cell by active transport process
such as,
Phagocytosis , ( phago =eat )
1)Endocytosis Endo = inside, within
Pinocytosis , ( pino = drink )
2)Exocytosis Exo = external ,out
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5. ENDOCYTOSIS AND EXOCYTOSIS
▪ Both require energy.
▪ Large particles are transported across the membrane in
membrane bound vesicles.
ENDOCYTOSIS
The process where a cell absorb extracellular material by
engulfing it with their cell membrane to form a vesicle which
is then pinched off intracellularly.
These particles does not pass through the membrane, it is
simply engulfed and enclosed.
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8. * The reverse process where materials
are expelled or secreted from a cell.
* This is used to rid wastes and secreted
substances (hormones) produced by the
cell.
* It may be excretion or secretion.
EXOCYTOSIS

10. PHAGOCYTOSIS
PHAGOCYTOSIS (SOLID PARTICLES – CELL EATING) .
▪ This is carried by specialized cells of mononuclear phagocyte system called
phagocytes by absorption of specific blood component called ‘opsonins’.
▪ Phagocytic vacuole fuses with one or more lyosomes to form
phagolysosomes.
▪ Digestion of particles occurs by lyosomal acid hydrolysis , making drug
available to exert its effect.
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11. PINOCYTOSIS
PINOCYTOSIS (LIQUID – CELL DRINKING).
▪ Pinocytosis (a form of endocytosis) allows a cell to engulf large molecules
and fluid that may be present in the extracellular region.
▪ The cell membrane folds inwards , encloses the fluid or particle to be
transported and then fuses to form a vesicle.
▪ The vesicle detaches from the membrane and moves to the interior of the
cell.
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13. TYPES OF PINOCYTOSIS
It is of two types
Fluid phase pinocytosis Receptor mediated pinocytosis
Fluid phase pinocytosis,
is non-specific & continuous process where macromolecules adheres to
general cell surface site.
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15. Receptor mediated pinocytosis
 is a specific process where the macromolecules bind to
specific cell receptor site.
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16. ▪ Receptor-mediated pinocytosis is a
particularly efficient form of pinocytosis.
▪ A receptor on the surface of the cell binds
to a molecule in the tissue fluid and the
complex of binding molecule (ligand) and
receptor is ingested .
▪ For example, this is how human cells take
in the element iron, which is present in
the tissue fluid bound to a protein called
transferrin.

17. TRANSPORT ACROSS
EPITHELIAL BARRIER
 Oral, buccal, nasal, vaginal and rectal cavities are internally lined
with one or more layers of epithelial cells.
 Depending on position and function in body, these cells vary.
These cells are extremely cohesive.
 Absorption of low molecular weight drugs from oral route is well
established.
 Various transport process used frequently by drugs to cross
epithelial barrier lining are,
• Passive diffusion
• Carrier mediated.
• Endocytosis
 Additionally, polar molecules can diffuse through tight junction
of epithelial cells i.e., paracellular route.

18. ▪ Molecules less than 10 kDa are absorbed from nasal epithelium into
systemic circulation in sufficient amount without need of added
materials.
▪ Large molecule proteins (e.g., interferon, human growth hormone)
requires both penetration enhancer & bioadhesives.
▪ This flux enhancers deleterious effect
Nasal mucosa & mucociliary clearance.
cyclodestrins
 Overcomed by,
phospholipids 18

19. Phospholipids,
 significant increase in absorption of macromolecules.
 Biocompatible
 bioresorbable
 no or less threat of toxicity
Penetration enhancers
 improves intestinal absorption of peptides & other macromolecular drugs.
 These includes: a) Chelators: e.g., EDTA, citric acid, salicylates etc.
b) Surfactants: Natural ,Semi synthetic ,Synthetic.
c) Fatty acid & derivatives : e.g., oleic acid, sodium laurate, sodium caprate etc.
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20. Factors influencing the absorption of drugs from
gastrointestinal tract :
▪ pH
▪ Enzymes
▪ surface area
▪ microflora
▪ transit time. 20

21. EXTRAVASATION
DEFINATION
For a drug to exert its therapeutic effects, it must move from the central
circulation and interact with its extra vascular-extracellular or extra vascular-
intracellular target. This process of transvascular exchange is called
“extravasation.”
Extravasation is governed by ,
▪ permeability through blood capillary walls
▪ Rate of blood & lymph
▪ Physicochemical factors like,
1) molecular shape, size and charge of drug
2) and its Hlb characteristics
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22. Depending on the morphology & continuity of endothelial layer &
basement membrane , blood capillaries are of three types:
▪ Continuous
▪ Fenestrated
▪ sinusoidal
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23. Continuous capillaries –
▪ These are common and widely distributed in the body.
▪ They exhibit tight interendothelial junctions and an uninterrupted basement
membrane.
Fenestrated capillaries –
▪ These show interendothelial gaps of 8-20 nm at regular intervals.
Sinusoidal capillaries –
▪ show 150 nm of interendothelial gaps.
▪ Basal membrane is absent in sinusoidal capillaries of liver and is discontinuous
in spleen and bone marrow. 23

24. LYMPHATIC UPTAKE
▪ Following extravasation, the drug molecules
can either reabsorb into the blood stream
directly by the enlarged post capillary
interendothelial cell pores found in most
tissues or enter into the lymphatic system
and then return with the lymph to the blood
circulation.
▪ Drugs administered through subcutaneous,
intramuscular, transdermal and peritoneal
routes reach the systemic circulation by
lymphatic system.
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26. LYMPHATIC CIRCULATION
Lymphatic circulation is a path of minor importance in drug absorption into systemic
circulation for two reasons:
1) The lymph vessels are less accessible than the capillaries.
2) The lymph flow is exceptionally slow.
 However, fats, fat-soluble vitamins & highly lipophilic drugs are absorbed through
lymphatic circulation.
Advantage of lymphatic absorption of drugs:
 Avoidance of first pass effect.
 Compounds of high molecular weight (above 16,000) can be absorbed by lymphatic
transport.
 Targeted delivery of drugs to lymphatic system as in certain case of cancer is possible.26

27. RETICULOEDNOTHELIAL SYSTEM (RES)
▪ Reticuloendothelial (RES) System
Comprised of a set of mononuclear
phagocytic cells which originate from
precursors in bone marrow, enter blood
stream as monocytes and pass into
various tissues where they differentiate
into macrophages.
▪ Macrophages are essential part of
defense function.
▪ An important function of macrophages
is to engulf and remove circulating
pathogens, tissue debris and damaged
macromolecules .
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28. ▪ RES is also involved in formation of new R.B.C & W.B.C by
destruction of older ones.
▪ Since macrophages are concentrated at site of inflammation such
as tumors, drug targeting is thus achievable.
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29. REFERENCES
▪ Modern Pharmaceutics ( Gilbert s. banker, 4 th edition)
▪ Targeted drug delivery system (vyas & khar )
▪ Biopharmaceutics & pharmacokinetics( Brahmankar )
▪ Cell Biology (S.C Rastogi)
▪ Anatomy & physiology (k. sambulingam)
▪ google.com
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