Drug carrier systems targeted to widely dispersed cells

Drug Carrier Systems Targeted to Widely

Dispersed Cells

Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D

Department of PharmaceuticsKLE 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.


Biological systems and Carrier nanostructures

05 March 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 3

Targeted Drug Carrier


Targeting of drug carriers


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


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.


Passive targeting


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.


Antibody Function


•Antigen–Antibody Complex = An antibody bound to an antigen

Active and Passive targeting


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.


Nanotechnology – based drug delivery Systems


Delivery to macrophages


Macrophages


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


Alveolar macrophage


Drug Carrier System

• Lipidic

• Proteic

• Polymeric

• Technology to provide new sustained drug delivery with better body distribution


Lipidic Carrier Systems


Proteic Carrier Systems


Polymeric Carrier Systems


(1) Receptor mediated endocytosis (2) Non specific transcellular transport(3) Paracellular transport (4) M cell mediated transport

Polymeric Micelle and its dimensions


Pharmaceutical Micelles


Polymeric Dendrimers


Drug Carrier System Technology

• Microspongs• Nanoparticles• Microemulsion and Nanoemulsion• Cyclodextrins• Metal nanoparticles and quantum dots• Immunoconjugates• Virus

05 March 2013DDSEC, Prince of Songkla University, Hat

Yai, Thailand.25

Nanoparticles specific targeting


(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


Targeting to macrophages


Delivery to lymphoid cells of Immune

network


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)


Human lymphocyte


Cell membrane


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


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


Virosomes /Drug Carrier


Drug Delivery to Tumours


Immune surveillance


Delivery to Lysosomal Storage

Diseases


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


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.


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.


Lysosomal targeting of a Cell


Therapies for Lysosomal Storage Diseases


Thank youE-mail: [email protected]

Cell No: 00919742431000


Drug carrier systems targeted to widely dispersed cells

Health & Medicine

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