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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: nanjwadebk@gmail.com. CONTENT.
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Drug Carrier Systems Targeted to Widely Dispersed Cells Prof. Dr. Basavaraj K. NanjwadeM. Pharm., Ph. D Department of Pharmaceutics KLE University College of Pharmacy, BELGAUM-590010, Karnataka, India. Cell No.: 0091-9742431000 E-mail: nanjwadebk@gmail.com DDSEC, Prince of Songkla University, Hat Yai, Thailand.
CONTENT • Delivery to macrophages. • Delivery to lymphoid cells of immune network. • Delivery to lysosomal storage diseases. DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Biological systems and nanostructures DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Targeted Drug Carrier/ Delivery System DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Physical targeting of drugs/drug carriers DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Threelevels of targeting • First order targeting or organ targeting • Second order targeting or cellular targeting • Third order targeting or subcellular targeting DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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. DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Passive targeting DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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. DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Antibody Function • Antigen–Antibody Complex = An antibody bound to an antigen DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Active and Passive targeting DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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. DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Nanotechnology – based drug delivery Systems DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Delivery to macrophages DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Macrophages DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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 DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Alveolar macrophage DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Drug Carrier System • Lipidic • Proteic • Polymeric • Technology to provide new sustained drug delivery with better body distribution DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Lipidic Carrier Systems DDSEC, Prince of Songkla University, Hat Yai, Thailand.
ProteicCarrier Systems DDSEC, Prince of Songkla University, Hat Yai, Thailand.
PolymericCarrier Systems (1) Receptor mediated endocytosis (2) Non specific transcellular transport (3) Paracellular transport (4) M cell mediated transport DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Polymeric Micelle and its dimensions DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Pharmaceutical Micelles DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Polymeric Dendrimers DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Drug Carrier System Technology • Microspongs • Nanoparticles • Microemulsion and Nanoemulsion • Cyclodextrins • Metal nanoparticles and quantum dots • Immunoconjugates • Virus DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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 DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Targeting to macrophages DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Delivery to lymphoid cells of Immune network DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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) DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Human lymphocyte DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Cell membrane DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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 DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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 DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Nanoparticles specific targeting (A) protective polymer with targeting ligand/probe copulated; (B) Antibody; (C) Enzyme; (D) Complexation with DNA; (E) protective polymer; (F) ligand. DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Drug Delivery to Tumours DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Immune surveillance DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Delivery to Lysosomal Storage Diseases DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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 DDSEC, Prince of Songkla University, Hat Yai, Thailand.
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. DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Causes for LSD’S • Defects in the lysosomal function 2. Defects in the hydrolytic enzymes 3. Defects in post translational processing of lysosomal enzymes. DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Lysosomal targeting of a Cell DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Therapies for Lysosomal Storage Diseases DDSEC, Prince of Songkla University, Hat Yai, Thailand.
Thank youE-mail: nanjwadebk@gmail.comCell No: 00919742431000 DDSEC, Prince of Songkla University, Hat Yai, Thailand.