Transcript Drug Targeting to Particular Organs

Drug Carrier Systems
Targeted to Widely Dispersed
Cells
Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D
Department of Pharmaceutics
KLE University College of Pharmacy,
BELGAUM-590010, Karnataka, India.
Cell No.: 0091-9742431000
E-mail: [email protected]
05 March 2013
DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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CONTENT
• Delivery to macrophages.
• Delivery to lymphoid cells of immune
network.
• Delivery to lysosomal storage diseases.
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Biological systems and
nanostructures
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Targeted Drug Carrier/
Delivery System
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Physical targeting of
drugs/drug carriers
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Three levels of targeting
1. First order targeting or organ targeting
2. Second order targeting or cellular targeting
3. Third order targeting or subcellular targeting
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First order targeting or
Organ targeting
• Drug delivery system releases the drug only in
a specific organ it is called as organ targeting.
• Targeted to the liver because its vasculature is
normally leaky or fenestrated or “ having loose
junctions”.
• In this case drug is not released in other
tissues because their vasculature is not leaky.
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Passive targeting
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Second order targeting or
Cellular targeting
• Drug delivery system releases the drug to a
particular cell within an organ or tissue it is
called as second order or cellular targeting.
• An antibody, specifically recognizes and
attaches to a specific antigen on a cell surface.
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Antibody Function
•Antigen–Antibody
Complex = An antibody
bound to an antigen
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Active and Passive targeting
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Third order targeting or
Subcellular targeting
• Drug delivery system can enter specific cells
and leave the drug intracellularly, then, it is
called a third order or subcellular targeting
process.
• The delivery system carries the gene; it enters
specific
cells
and
leaves
the
gene
intracellularly and its sophisticated variety of
targeting.
05 March 2013
DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Nanotechnology – based
drug delivery Systems
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Delivery to macrophages
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Macrophages
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What is a Macrophage?
• Macrophages are white blood cells within
tissues, produced by the division of monocytes.
• Macrophage is the removal of necrotic cellular
debris in the lungs.
• Macrophage as secretory cells
• In some cases, pathogens are very resistant to
adhesion by the macrophages
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Alveolar macrophage
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Drug Carrier System
• Lipidic
• Proteic
• Polymeric
• Technology to provide new sustained drug
delivery with better body distribution
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Lipidic Carrier Systems
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Proteic Carrier Systems
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Polymeric Carrier Systems
(1) Receptor mediated endocytosis (2) Non specific transcellular transport
(3) Paracellular transport (4) M cell mediated transport
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Polymeric Micelle and its
dimensions
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Pharmaceutical Micelles
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Polymeric Dendrimers
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Drug Carrier System
Technology
•
•
•
•
•
•
•
Microspongs
Nanoparticles
Microemulsion and Nanoemulsion
Cyclodextrins
Metal nanoparticles and quantum dots
Immunoconjugates
Virus
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Yai, Thailand.
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Drug Carrier System
Technology
• Vesicular
carrier
system:
Liposomes,
Transferosomes,
Ethosomes,
Niosomes,
Virosomes, Cochleate, Cubosomes, Solid lipid
nanoparticles (SLN), Nanostructure lipid
carriers (NLC)
• Polymers: Dendrimers, Polymeric Micelles,
Natural
and
Synthetic
Polymeric
Nanoparticles
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Yai, Thailand.
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Targeting to macrophages
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Delivery to lymphoid
cells of Immune network
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Lymphoid cell
• Lymphoid cells lack granules, have a compact
nucleus, and a transparent cytoplasm.
• They are involved in producing immunity.
Two main divisions:
• Cell mediated immunity (T cell)
• Antibody mediated immunity (B cell)
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Human lymphocyte
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Cell membrane
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B Cells
• Responsible for antibody-mediated immunity
• Defends against antigens and pathogens in
body fluids
• Attack antigens by producing specific
antibodies
• Corresponding antigens in interstitial fluids
bind to B cell receptors
• B cell prepares for activation
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T Cells
• Provide cell-mediated immunity
• Defends against abnormal cells and pathogens
inside cells
• T cells only recognize antigens that are bound
to glycoproteins in cell membranes
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Nanoparticles specific
targeting
(A) protective polymer with targeting ligand/probe copulated; (B) Antibody;
(C) Enzyme; (D) Complexation with DNA; (E) protective polymer; (F) ligand.
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Drug Delivery to Tumours
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Immune surveillance
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Delivery to Lysosomal
Storage Diseases
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Lysosomal Storage Diseases
• Lysosomes
system.
are
the
cell's
waste
disposal
• Lysosomes Helps in repair damage to the
plasma membrane by serving as a membrane
patch,
sealing
the
wound.
• LSDs occur with incidences of less than
1:100,000
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Lysosomal Storage Diseases
• Lysosomes break down unwanted matter via
enzymes, highly specialized proteins essential
for survival.
• The lysosome doesn’t function normally, excess
products destined for breakdown and recycling
are stored in the cell.
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Causes for LSD’S
1. Defects in the lysosomal function
2. Defects in the hydrolytic enzymes
3. Defects in post translational processing of
lysosomal enzymes.
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Lysosomal targeting of a Cell
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Therapies for Lysosomal
Storage Diseases
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Thank you
E-mail: [email protected]
Cell No: 00919742431000
05 March 2013
DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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