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DELIVERY OF PROTEINS: ROUTES OF ADMINISTRATION AND ABSORPTION ENHANCEMENT. Parenteral Route of Administration. Intravenous (IV ) Intramuscular (IM ) S ub-cutaneous (SC ) Intraperitoneally ( IP) Intraosseous (IO). Lymphatic System. One way system: to the heart
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(lymph nodes destroy most pathogens)
Preferable way but;
(ii) poor permeability
amino acids at acidic ph.
Other endopeptidases ( trypsin, chymo-trypsin, and elastase)
are active in the GI tract at neutral pH values
Exopeptidases(carboxypeptidaseA and B)
-The oral route of administration for therapeutic proteins is not the best choice till now.
only a (small) fraction of the antigen (protein) has to reach lymphocytes and antigen presenting accessory cells located in Peyer’s patches.
The B-lymphocyte population includes cells that produce secretory IgA antibodies
microfold (M) cells
little lysosomal degradation capacity
Goblet cell density is reduced over Peyer’s patches.
This facilitates access to the M cell
To improve antigen delivery via the Peyer’s patches and to enhance the immune
response by using microspheres, liposomes or modified live vectors, such as attenuated bacteria and viruses have been used.
The nose, lungs, rectum, oral cavity, and skin have been selected as potential sites of application.
Nasal, buccal, rectal, and transdermal routes needs absorption enhancing
-The bioavailability in rats of intratracheally
administered protein solutions with a wide range of molecular weights.
-In humans the drug should be inhaled instead of intratracheallyadminstered
The first pulmonary insulin formulation was
approved by FDA in January 2006
Uptake of insulin is faster than after a regular SC insulin injection (peak 5–60 minutes versus 60–180 minutes).
We still look to develop a system that temporarily decreases the absorption barrier resistance with minimum and acceptable safety concerns
- Absorption Enhancing Effects
enhancers in general act by following ways :
1. Increasing the fluidity of the cell membrane
2. Extracting inter and intracellular lipids
3. Disrupting lipid structure e.g., solubilization by
formation of micelles to create aqueous channels
4. Altering cellular proteins
5. Increasing the thermodynamic activity of the
6. Overcoming enzymatic barriers, particularly for
peptide and protein drugs
7. Altering surface mucin rheology
Sodium glycodeoxycholate acts in the intercellular lipid domain at lower concentrations (2 mM), apparently reducing the amount of polar lipids, whereas disorganizing cell membrane lipids at higher concentrations
Generally, they act reversibly without producing major damage to the mucosa. Bile salts used in permeation enhancement studies include the trihydroxy salts sodium cholate, sodium glycocholate, and sodium taurocholate and the dihydroxy salt sodium deoxycholate, sodium glycodeoxycholate, and sodium taurodeoxycholate.
being addressed are reproducibility, effect of pathological conditions on absorption and
safety aspects of chronic use. Interestingly, absorption enhancing effects were shown to be species dependent. Pronounced differences in effect were observed
between rats, rabbits, and humans.
Iontophoresisa transdermal electrical current is induced by positioning two electrodes on different places on the skin