Drug Carrier Systems Targeted to Widely Dispersed Cells Prof. Dr. Basavaraj K. Nanjwade M. Pharm.,...
-
Upload
abraham-wilcox -
Category
Documents
-
view
216 -
download
0
description
Transcript of Drug Carrier Systems Targeted to Widely Dispersed Cells Prof. Dr. Basavaraj K. Nanjwade M. Pharm.,...
Drug Carrier Systems Targeted to Widely
Dispersed CellsProf. Dr. Basavaraj K. Nanjwade M.
Pharm., Ph. DDepartment of Pharmaceutics
KLE University College of Pharmacy,BELGAUM-590010, Karnataka, India.
Cell No.: 0091-9742431000E-mail: [email protected]
05 March 2013 1DDSEC, Prince of Songkla University, Hat Yai, Thailand.
CONTENT• Delivery to macrophages.
• Delivery to lymphoid cells of immune network.
• Delivery to lysosomal storage diseases.
05 March 2013 2DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Biological systems and nanostructures
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 3
Targeted Drug Carrier/ Delivery System
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 4
Physical targeting of drugs/drug carriers
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 5
Three levels of targeting1. 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. 6
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. 7
Passive targeting
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 8
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. 9
Antibody Function
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 10
•Antigen–Antibody Complex = An antibody bound to an antigen
Active and Passive targeting
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 11
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. 12
Nanotechnology – based drug delivery Systems
05 March 2013 13DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Delivery to macrophages
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 14
Macrophages
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 15
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. 16
Alveolar macrophage
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 17
Drug Carrier System• Lipidic
• Proteic
• Polymeric
• Technology to provide new sustained drug delivery with better body distribution
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 18
Lipidic Carrier Systems
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 19
Proteic Carrier Systems
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 20
Polymeric Carrier Systems
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 21
(1) Receptor mediated endocytosis (2) Non specific transcellular transport
(3) Paracellular transport (4) M cell mediated transport
Polymeric Micelle and its dimensions
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 22
Pharmaceutical Micelles
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 23
Polymeric Dendrimers
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 24
Drug Carrier System Technology
• Microspongs• Nanoparticles• Microemulsion and Nanoemulsion• Cyclodextrins• Metal nanoparticles and quantum dots• Immunoconjugates• Virus
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 25
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
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 26
Targeting to macrophages
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 27
Delivery to lymphoid cells of Immune network
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 28
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)
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 29
Human lymphocyte
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 30
Cell membrane
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 31
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
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 32
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
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 33
Nanoparticles specific targeting
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 34
(A) protective polymer with targeting ligand/probe copulated; (B) Antibody; (C) Enzyme; (D) Complexation with DNA; (E) protective polymer; (F) ligand.
Drug Delivery to Tumours
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 35
Immune surveillance
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 36
Delivery to Lysosomal
Storage Diseases05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 37
Lysosomal Storage Diseases
• Lysosomes are the cell's waste disposal system.
• 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
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 38
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.
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 39
Causes for LSD’S1. 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. 40
Lysosomal targeting of a Cell
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 41
Therapies for Lysosomal Storage Diseases
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 42
Thank youE-mail: [email protected]
Cell No: 00919742431000
05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 43