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RECENT TRENDS IN DRUG DELIVERY SYSTEM:LYMPHATIC DRUG TARGETING AND TRANSPORTATION:

RECENT TRENDS IN DRUG DELIVERY SYSTEM:LYMPHATIC DRUG TARGETING AND TRANSPORTATION Department Of Pharmaceutics Malla Reddy Institute Of Pharmaceutical Sciences, Maisammaguda , Secunderabad – 500014 April 2012 Under the esteemed guidance of Dr.R,S.Karthikeyan . M.Pharm.,Ph.D . PRESENTED BY: K.SWETHA M.Pharmacy , 1 st semister .

CONTENTS:

CONTENTS INTRODUCTION COMPONENTS OF THE LYMPHATIC SYSTEM PHYSIOLOGY SOLUTION UPTAKE ADMINISTRATION APPLICATIONS TREATMENT CONCLUSION

INTRODUCTION:

INTRODUCTION Drug delivery is a special form of the system where the pharmacologically active agent or a medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells. The drug that targeted may be delivered To the capillary bed of the active sites To the specific organ (or) tissues by complexing with the carrier that recognizes the target

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Targeting of drugs to lymphatic system is usually attained by utilizing carriers like microspheres, nanoparticles and liposomes . The first objective is explained by the targeting of certain anti-cancer agents in some lymphomas and in tumor detection in lymph nodes using radio labeled liposomes . The other objective is explained by the transport of anti- inflamatory agents to the site of inflammation

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LYMPHATIC SYSTEM: The lymphatic system has three primary functions . It returns excess interstitial fluid to the blood. 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 third is defence against invading microorganisms and diseases .

COMPONENTS::

COMPONENTS: The lymphatic system consists of lymph, vessels and organs that contain lymphoid tissue. Lymph : Lymph is a fluid similar in composition to blood plasma, when the interstitial fluid enters the lymph capillaries, it is called lymph . Lymphatic vessels: The wall of the lymph capillary is composed of endothelium, it permits fluid to enter the capillary but prevents lymph from leaving the vessel.

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LYMPHATIC ORGANS These are characterized by clusters of lymphocytes and other cells, such as macrophages. The lymphocytes originate in the red bone marrow and are carried to the lymphatic organs. The lymphatic organs include: lymph nodes Tonsils Spleen Thymus

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LYMPH NODES Lymph nodes are small bean-shaped structures that are usually less than 2.5 cm in length. There are three superficial regions on each side of the body where lymph nodes tend to cluster . These areas are the inguinal nodes in the groin, the axillary nodes in the armpit, and the cervical nodes in the neck . The typical lymph node is surrounded by a connective tissue capsule and divided into compartments called lymph nodules.

PHYSIOLOGY::

PHYSIOLOGY: The lymphatic system is a drainage system, collecting and returning intestinal fluids. This system is a network of capillaries and tubes called lymphatics . Lymphocytes in the lymph nodes aid the body in fighting infection by producing antibodies that destroy bacteria and viruses. The main functions of the lymphatic system are fluid and protein balance, immunity and spread of infection, digestion and solute uptake.

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EFFECT OF PARTICLE SIZE ON LYMPHATIC TRANSPORT

SOLUTE UPTAKE BY LYMPHATIC SYSTEM::

SOLUTE UPTAKE BY LYMPHATIC SYSTEM: The endothelial cell junctions of the initial lymphatics are not tight and considered freely permeable to most proteins, the physico - chemical properties of the extracellular membrane can affect interstitial solute transport. Significant changes in lymph concentration occur as the fluid passes through various components of the lymphatic system. It becomes concentrated along the contracting lymphangion segments, possibly due to water filtration across the vessel wall.

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The size, shape, charge and lipophilicity of a molecule affect its uptake rate. Molecules that are smaller than 10 nm are reabsorbed into the blood capillaries, the optimal size for lymphatic uptake is 10-100 nm. The larger the particle, the more is the selectivity for uptake into the lymphatic system but the slower the uptake. Colloids and lipids have high uptake efficiencies. Depending on the size, charge, method of preparation and composition, various molecules such as monoclonal antibodies, peptide drugs and anticancer agents may be encapsulated into liposomes , nanoparticles and optimally targeted to lymph nodes.

LYMPHATIC DRUG TARGETING THROUGH ORAL ROUTE::

LYMPHATIC DRUG TARGETING THROUGH ORAL ROUTE: The stomach, intestines and related organs of the gastrointestinal tract are drained along the lymphatics with the vessels supplying these organs . These nodes are finally drained into the cisterma chili. These are regions in the git , especially in small intestine, called Payer’s Patches. Absorbed microspheres then reaches the mesentery via the mesenteric lymph nodes and were transported from the lymphatic circulation into the venous circulation and subsequently into the liver.

LYMPHATIC DRUG TARGETING THROUGH PARENTARAL ROUTE::

LYMPHATIC DRUG TARGETING THROUGH PARENTARAL ROUTE: Most compounds of relatively small molecular weight are exclusively absorbed via splenic blood capillaries into the portal vein. Many drugs in solution injected into sc or im sites behave as if their absorption is through capillaries, lymphatics , or both. There are other factors such as area of the drug depot formed after injection, volume of the injection, drug concentration, age , the tissue condition affect the rate of diffusion, the molecular size of the drug or the particle size of the carrier determines whether it will be absorbed via the capillaries or the lymphatics .

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Molecules with MW>16,000 are absorbed mainly by the lymphatics but compounds with MW<1000 are hardly absorbed at all by the lymphatic vessels. An increasing tendency towards lymphatic absorption was determined for molecules with a MW between 1000 and 16000. Although passive diffusion is an important mechanism for drug absorption the process of endocytosis may also be involved in drug absorption from sc and im sites .

APPLICATIONS::

APPLICATIONS: CONTROLED DRUG DELIVERY SYSTEMS: Controlled drug delivery technology offers numerous advantages compared to conventional dosage forms, including improved efficacy, reduced toxicity, and improved patient compliance and convenience. Two types of controlled drug release can be achieved, temporal and distribution control. In temporal control, drug delivery systems aim to deliver the drug over an extended duration or at a specific time during treatment. In distribution control, drug delivery systems aim to target the release of the drug to the precise site of activity within the body.

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There are two principle situations in which distribution control can be beneficial. The first is when the natural distribution causes drug molecules to encounter tissues and cause major side effects that prohibit further treatment. The second situation is when the natural distribution of the drug does not allow drug molecules to reach their site of action . Systems using either of these two mechanisms have been developed for clinical therapy.

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CANCER CHEMOTHERAPY: Radiation therapy is commonly used in adjuvant treatment for pancreatic cancer after radical surgery. The effect of radiation with concurrent 5-FU based chemotherapy has been suggested in a number of randomized clinical trials. Concurrent chemo-radiation therapy has been the mainstay treatment for non metastatic and inoperable pancreatic cancer.

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The aim of this analysis is to address the selection of high-risk subclinical lymph nodal regions in conformal radiation therapy for resectable pancreatic cancer, by reviewing and summarizing the probability of lymph node metastases in resectable pancreatic cancer patients treated with radical surgery with lymph node dissection and pathological investigation of the resected regional node.

TREATMENT OF INFECTION::

TREATMENT OF INFECTION: A number of human diseases have been linked to abnormal or defective lymphatic vessels. The theory of anti-angiogenesis therapy has been extensively studied, the concept of targeting lymphangiogenesis to gain a therapeutic advantage in human disease is only a recent development. Therapeutic options which target cellular pathways may provide a means to prevent growth from the primary tumor. Therapeutics may be either anti-lymphatic and/or anti- lymphangiogenic .

CONCLUSION:

CONCLUSION Lymphatic drug targeting and transportation can be an important phenomenon for the absorption and delivery of drugs, and aimed at specifically in the case of carriers for peptides for avoiding hepatic first pass metabolism, for tumor detection and its treatment. Lymphatic drug delivery is in its infancy, but localized treatments of the lymphatics will decrease systemic toxicities associated with cytotoxic chemotherapy and reduce recurrence owing to residual local disease. By increasing our understanding of the role of lymphatics in cancer spread, we can design new therapeutics that supplement or even replace radiotherapy for local disease control.

REFERENCES:

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