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 , Karnataka, India. Cell No.: March 20131DDSEC, 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 20132DDSEC, Prince of Songkla University, Hat Yai, Thailand.

Biological systems and Carrier nanostructures 05 March 2013DDSEC, Prince of Songkla University, Hat Yai, Thailand.3

Targeted Drug Carrier 05 March 2013DDSEC, Prince of Songkla University, Hat Yai, Thailand.4

Targeting of drug carriers 05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 5

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. 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 2013DDSEC, 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 DDSEC, Prince of Songkla University, Hat Yai, Thailand.

Delivery to macrophages 05 March 2013DDSEC, 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 2013DDSEC, 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 2013DDSEC, Prince of Songkla University, Hat Yai, Thailand.19

Proteic Carrier Systems 05 March 2013DDSEC, Prince of Songkla University, Hat Yai, Thailand.20

Polymeric Carrier Systems 05 March 2013DDSEC, 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 2013DDSEC, Prince of Songkla University, Hat Yai, Thailand.22

Pharmaceutical Micelles 05 March 2013DDSEC, 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

Nanoparticles specific targeting 05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 26 (A) protective polymer with targeting ligand/probe copulated; (B) Antibody; (C) Enzyme; (D) Complexation with DNA; (E) protective polymer; (F) ligand.

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 05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 27

Targeting to macrophages 05 March 2013DDSEC, Prince of Songkla University, Hat Yai, Thailand.28

Delivery to lymphoid cells of Immune network 05 March 2013DDSEC, Prince of Songkla University, Hat Yai, Thailand.29

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. 30

Human lymphocyte 05 March 2013DDSEC, Prince of Songkla University, Hat Yai, Thailand.31

Cell membrane 05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 32

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. 33

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. 34

Virosomes /Drug Carrier 05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 35

Drug Delivery to Tumours 05 March 2013DDSEC, Prince of Songkla University, Hat Yai, Thailand.36

Immune surveillance 05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 37

Delivery to Lysosomal Storage Diseases 05 March 2013DDSEC, Prince of Songkla University, Hat Yai, Thailand.38

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, March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 39

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. 40

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. 41

Lysosomal targeting of a Cell 05 March 2013DDSEC, Prince of Songkla University, Hat Yai, Thailand.42

Therapies for Lysosomal Storage Diseases 05 March 2013DDSEC, Prince of Songkla University, Hat Yai, Thailand.43

Thank you Cell No: 05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 44