Clarification of Answer by
crabcakes-ga
on
09 Jun 2005 13:28 PDT
Hi again saregamapa,
Even though your clarification asks a different question than your
original question, I have attempted to supply you with a better
understanding of the lymphatic system and drug transport into the
lymphatic system.
?Small quantities of very small fatty acids are able to directly enter
the intestinal capillaries of the villi of the small intestine and
hence enter the blood stream in this way. However, the majority of
fatty acids are long chained and are absorbed quite differently.
Within the intestinal lumen, bile salts form aggregates called
micelles that are water soluble. Fatty acids and monoglycerides are
aggregated into the centres of the micelles. The micelles transport
the fatty acids and monoglycerides to the brush borders of the villi.
From here, the fatty acids and monoglycerides diffuse into the
epithelial cells of the villi. The micelles continue their ferrying
function in the intestinal lumen. Within the epithelial cells, the
fatty acids and monoglycerides are resynthesised into triglycerides.
The triglycerides combine with cholesterol, lipoprotein, and
phospholipids to form globules called chylomicrons. The chylomicrons
leave the epithelial cells and enter into the lacteal of the villus.
Lymphatic vessels then carry the chylomicrons to the venous blood of
the left subclavian vein via the thoracic duct.?
http://www.jdaross.mcmail.com/lymphatic_system.htm
?Absorption from solid forms: Most drugs are given orally as tablets
or capsules primarily for convenience, economy, stability, and patient
acceptance. These products must disintegrate and dissolve before
absorption can occur. Disintegration greatly increases the drug's
surface area in contact with GI fluids, thereby promoting drug
dissolution and absorption. Disintegrants and other excipients (eg,
diluents, lubricants, surfactants, binders, dispersants) are often
added during manufacture to facilitate these processes. Surfactants
increase the dissolution rate by increasing the wetability,
solubility, and dispersibility of the drug. Disintegration of solid
forms may be retarded by excessive pressure applied during the
tableting procedure or by special coatings applied to protect the
tablet from the digestive processes of the gut. Hydrophobic lubricants
(eg, magnesium stearate) may bind to the active drug and reduce its
bioavailability.
Dissolution rate determines the availability of the drug for
absorption. When slower than absorption, dissolution becomes the
rate-limiting step. Overall absorption can be controlled by
manipulating the formulation. For example, reducing the particle size
increases the drug's surface area, thus increasing the rate and extent
of GI absorption of a drug whose absorption is normally limited by
slow dissolution. Dissolution rate is affected by whether the drug is
in salt, crystal, or hydrate form. The Na salts of weak acids (eg,
barbiturates, salicylates) dissolve faster than their corresponding
free acids regardless of the pH of the medium. Certain drugs are
polymorphic, existing in amorphous or various crystalline forms.
Chloramphenicol palmitate has two forms, but only one sufficiently
dissolves and is absorbed to be clinically useful. A hydrate is formed
when one or more water molecules combine with a drug molecule in
crystal form. The solubility of such a solvate may markedly differ
from the nonsolvated form; eg, anhydrous ampicillin has a greater rate
of dissolution and absorption than its corresponding trihydrate.?
http://www.merck.com/mrkshared/mmanual/section22/chapter298/298b.jsp
?The plasma lipoprotein distribution of potential drug candidates is
not commonly studied. For some hydrophobic drug candidates, attainment
of similar plasma free drug levels has not been associated with
uniform production of pharmacological activity in different animal
species. It is well known that plasma lipoprotein lipid profiles vary
considerably between different animal species. In addition, human
disease states can significantly influence plasma lipoprotein
profiles, resulting in altered drug therapeutic outcomes. A plausible
explanation for these findings may be a result of lipoprotein drug
transport within the systemic circulation. Elucidation of the
mechanisms that dictate the lipoprotein binding of drugs may yield
valuable insight into the factors governing the pharmacological
activity and potential toxicity of these compounds. Furthermore,
utilizing these factors to target compounds specifically to one
lipoprotein subclass over another potentially could improve the drug's
efficacy and safety.?
http://www.pharmacy.ubc.ca/faculty_staff/faculty/pharm_bio/pharm_bio_kishor_wasan.html
?The second function of the lymphatic system is the absorption of fats
and fat-soluble vitamins from the digestive system and the subsequent
transport of these substances to the venous circulation. The mucosa
that lines the small intestine is covered with fingerlike projections
called villi. There are blood capillaries and special lymph
capillaries, called lacteals, in the center of each villus. The blood
capillaries absorb most nutrients, but the fats and fat-soluble
vitamins are absorbed by the lacteals. The lymph in the lacteals has a
milky appearance due to its high fat content and is called chyle.?
http://training.seer.cancer.gov/module_anatomy/unit8_1_lymph_functions.html
?The normal process of intestinal digestion can be divided into three
phases (Figure 4). During the intraluminal phase, ingested
carbohydrates, proteins and lipids are hydrolyzed within the
intestinal lumen by enzymes released by the salivary glands, the
stomach and the pancreas. In the intestinal phase, further digestion
of peptides and disaccharides continues at the level of the intestinal
brush border and the resulting amino acids, small peptides,
monosaccharides, monoglycerides and fatty acids are subsequently
absorbed into the enterocyte. The movement of nutrients from the
intestinal epithelial cell into the vascular or lymphatic circulation
defines the delivery phase. The overall absorptive capacity of the
intestinal tract depends upon its length and available surface
epithelium. In addition, some dietary substances have specific
intestinal sites of uptake. Bile acids, for example, are absorbed in
the ileum. Vitamin B12 first binds to intrinsic factor secreted by the
gastric parietal cell and is then absorbed by a specific
receptor-mediated process on ileal enterocytes.?
http://gastroresource.com/GITextbook/en/chapter15/15-7-pr.htm
?Return of excess filtered fluid. Normally, slightly more fluid is
filtered out of the capillaries into the interstitial fluid
(extracellular fluid) than is reabsorbed from the interstitial fluid
back into the plasma.
1.The average rate of flow through the lymph vessels is 3 liters per day.
2. Defense against pathogenic disease as the lymph percolates and is
filtered through the lymph nodes.
3. Transport of lipid (fat). The lymphatic system is important in the
absorption of fat from the small intestine. Dietary fat products are
packaged by the lining of the small intestine into particles which are
too large to gain entry into capillaries, but these particles can
easily access the lymphatics (lacteals = lymph capillaries in the
villi of the small intestine).?
http://www.biosbcc.net/barron/anatomy/pdf/LYMPHATIC%20SYSTEM.pdf
?Closely connected with the blood and circulatory system, the
lymphatic system is an extensive drainage system that returns water
and proteins from various tissues back to the bloodstream. It is
comprised of a network of ducts, called lymph vessels or lymphatics,
and carries lymph, a clear, watery fluid that resembles the plasma of
blood. Some scientists consider this system to be part of the blood
and circulatory system because lymph comes from blood and returns to
blood, and because its vessels are very similar to the veins and
capillaries of the blood system. Throughout the body, wherever there
are blood vessels, there are lymph vessels, and the two systems work
together.?
?This process is crucial because water, proteins, and other molecules
continuously leak out of tiny blood capillaries into the surrounding
body tissues. This lymph fluid has to be drained, and so it returns to
the blood via the lymphatic vessels. These vessels also prevent the
back flow of lymph fluid into the tissues.
The lymphatic system also helps defend the body against invasion by
disease-causing agents such as viruses, bacteria, or fungi. Harmful
foreign materials are filtered out by small masses of tissue called
lymph nodes that lie along the network of lymphatic vessels. These
nodes house lymphocytes (white blood cells), some of which produce
antibodies, special proteins that fight off infection. They also stop
infections from spreading through the body by trapping disease-causing
germs and destroying them.?
http://www.gorhams.dk/html/the_lymphatic_system.html
?For our bodies to function well in homeostasis, we need a lymph
system to carry off wastes, toxins, proteins, viruses, bacteria,
excess water, etc. from the connective tissue. The lymph system is
obliged to remove these substances that cannot be carried by the
venous capillaries, so we describe them as lymph-obligatory-load
(LOL).
Collection of the LOL is a vital function, just as the blood
circulation, nervous system, etc. are vital to our health. The LOL is
picked up by thin-walled, initial lymph vessels that originate in the
connective tissue and funnel LOL into collector lymph vessels. The
lymph vessels are fine, silk-like structures made of consecutive units
called angions. These onion-shaped units can function independently
and shift lymph from one unit to the next through one-way valves. The
larger angions have smooth muscle in their walls which contract and
squeeze the lymph to the next unit.?
http://www.healthtronix.com/overview.htm
You may find these articles interesting as well:
http://www.barnettinternational.com/RSC_PDFUploads/BI448WEB.pdf
http://www.freepatentsonline.com/4725442.html
http://www.drugdeliverytech.com/cgi-bin/articles.cgi?idArticle=10
I hope this extra information has been useful to you!
Sincerely, Crabcakes
