Download 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.
05 March 2013
DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Biological systems and
Carrier nanostructures
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Targeted Drug Carrier
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Targeting of drug carriers
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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
05 March 2013
DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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.
05 March 2013
DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Passive targeting
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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.
05 March 2013
DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Delivery to macrophages
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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
05 March 2013
DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Alveolar macrophage
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Lipidic Carrier Systems
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Proteic Carrier Systems
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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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Nanoparticles specific
targeting
(A) protective polymer with targeting ligand/probe copulated; (B) Antibody;
(C) Enzyme; (D) Complexation with DNA; (E) protective polymer; (F) ligand.
05 March 2013
DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Drug Carrier System
Technology
• Vesicular
carrier
system:
Liposomes,
Transferosomes,
Ethosomes,
Niosomes,
Virosomes,
Cubosomes,
Solid
lipid
nanoparticles (SLN), Nanostructure lipid
carriers (NLC)
• Polymers: Dendrimers, Polymeric Micelles,
Natural
and
Synthetic
Polymeric
Nanoparticles
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Targeting to macrophages
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Delivery to lymphoid cells
of Immune network
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Virosomes /Drug Carrier
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Drug Delivery to Tumours
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Immune surveillance
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Delivery to Lysosomal
Storage Diseases
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Lysosomal Storage Diseases
• Lysosomes break down unwanted matter via
enzymes, highly specialized proteins essential
for survival.
• A genetic defect in a protein responsible for
maintaining the lysosomal system results in
the accumulation within lysosomes of partially
degraded molecules, the initial step in the
process leading to a lysosomal storage disease.
05 March 2013
DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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.
05 March 2013
DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Lysosomal targeting of a Cell
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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Therapies for Lysosomal
Storage Diseases
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DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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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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