Targeted drug delivery system

Views:
 
Category: Education
     
 

Presentation Description

Concept,different approaches,physical, chemical,biological methods

Comments

Presentation Transcript

PowerPoint Presentation:

PRESENTED BY : ISHAD.PM FIRST YEAR, M.PHARM PHARMACEUTICS AL-SHIFA COLLEGE OF PHARMACY TARGETED DRUG DELIVERY SYSTEM

TARGETED DRUG DELIVERY SYSTEM:

A special form of drug delivery system where the pharmacologically active agent or medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells. TARGETED DRUG DELIVERY SYSTEM

PowerPoint Presentation:

Targeted drug delivery implies for selective and effective localization of pharmacologically active moiety at pre identified (preselected) target in therapeutic concentration, while restricting its access to non-target normal cellular linings, thus minimizing toxic effects and maximizing therapeutic index.

ADVANTAGES OF DRUG TARGETING:

Drug administration protocols may be simplified; Drug quantity may be greatly reduced as well as the cost of therapy; Drug concentration in the required sites can be sharply increased without negative effects on non-target compartments. ADVANTAGES OF DRUG TARGETING

DISADVANTAGES:

Rapid clearance of targeted systems. Immune reactions against intravenous administered carrier systems. Insufficient localization of targeted systems into tumour cells. Diffusion and redistribution of released drugs. DISADVANTAGES

IDEAL CHARACTERISTICS::

Targeted drug delivery system should be- biochemically inert (non-toxic), non-immunogenic. Both physically and chemically stable in vivo and in vitro. Restrict drug distribution to target cells or tissues or organs and should have uniform capillary distribution. Controllable and predictable rate of drug release. IDEAL CHARACTERISTICS:

PowerPoint Presentation:

Drug release should not affect the drug action. Therapeutic amount of drug release. Minimal drug leakage during transit. Carriers used must be bio-degradable or readily eliminated from the body without any problem. The preparation of the delivery system should be easy or reasonably simple, reproductive and cost effective.

CARRIERS:-:

Most important entity required for successful transportation of the loaded drug. Drug vectors which, retain and transport drug; deliver it within or in the vicinity of target. Do so through an inherent characteristic or acquired through structural modification. CARRIERS:-

PROPERTIES OF AN IDEAL DRUG CARRIER::

It must be able to cross anatomical barriers and in case of tumour chemotherapy tumour vasculature. It must be recognized specifically and selectively by the target cells and must maintain the specificity of the surface ligands. PROPERTIES OF AN IDEAL DRUG CARRIER:

PowerPoint Presentation:

The linkage of the drug and the directing unit (ligand) should be stable in plasma, interstitial and other biofluids. Carrier should be non-toxic, non- immunogenic and biodegradable particulate or macromolecule.

PowerPoint Presentation:

After recognition and internalization, the carrier system should release the drug moiety inside the target organs, tissues or cells.

TYPES:

Based on the nature of their origin: Endogenous - LDL ,HDL Chylomicrons, Serum albumin, Erythrocytes. Exogenous - Microparticulates, Soluble polymeric and Biodegradable polymeric drug carriers. TYPES

Pharmaceutical Carriers :

Polymers Microcapsules Microparticles Lipoproteins Liposomes Micelles Pharmaceutical Carriers

Targeting Moieties :

Antibodies Lectins and other proteins Lipoproteins Hormones Charged molecules Polysaccharides Low-molecular-weight ligands Targeting Moieties

CARRIER SYSTEMS USED FOR TARGETED DRUG DELIVERY :

CARRIER SYSTEMS USED FOR TARGETED DRUG DELIVERY

PowerPoint Presentation:

1. Colloidal carriers 2. Cellular carriers 3. Supramolecular delivery systems 4. Polymer based systems 5. Macromolecular carriers

Colloidal carriers: :

Vesicular systems - Liposomes , niosomes , pharmacosomes,virosomes,immunoliposomes . Microparticulate systems - Microparticles , Nanoparticles , Magnetic microspheres, Albumin microspheres, Nanocapsules . Colloidal carriers:

Cellular carriers: :

Erythrocytes, Serum albumin, Antibodies, Platelets, Leucocytes. Cellular carriers:

Supramolecular delivery systems:

Micelles ( Reverse, mixed, polymeric) liquid crystals, lipoproteins ( chylomicrons , VLDL,LDL ) Supramolecular delivery systems

Polymer based systems :

Signal sensitive, Muco-adhesive, Biodegradable, Bioerodible, Soluble synthetic polymeric carriers. Polymer based systems

Macromolecular carriers :

Proteins, glycoproteins , Neo glycoproteins and artificial viral envelopes (AVE). Glycosylated water soluble polymers (poly-L-lysine). Mabs , Immunological fragments, antibody enzyme complex and bispecific Abs. Toxins, immunotoxin . Lectins and polysaccharides. Macromolecular carriers

LEVELS OF DRUG TARGETING: :

1. Passive targeting 2. Inverse targeting 3. Active targeting (a) Ligand mediated targeting (b) Physical targeting LEVELS OF DRUG TARGETING:

4. Dual targeting 5. Double targeting 6. Combination targeting :

4. Dual targeting 5. Double targeting 6. Combination targeting

1.Passive targeting: :

Systems that target the systemic circulation. Devices include- drug bearing bilayer vesicular systems as well as cellular carriers of micron or submicron size range . 1. Passive targeting:

2.Inverse targeting: :

Based on attempts to circumvent and avoid passive uptake of colloidal carriers by RES, leading to reversion of bio distribution trend of the carrier . 2. Inverse targeting:

Strategy: :

The function of RES is suppressed by a pre-injection of colloidal carriers or macromolecules like dextran sulphate leading to RES blockade and resulting in impairment of host defense system. Alternative strategies include: modification of the size , surface charge,composition, surface rigidity & hydrophilicity of carriers for desirable biofate. Strategy:

3.Active targeting: :

The facilitation of the binding of the drug carrier to target cells by the use of ligands to increase receptor mediated localization of the drug and target specific delivery of drug is referred to as active targeting. 3. Active targeting:

3 types:

First order targeting(organ compartmentalization). Second order targeting (cellular targeting). Third order targeting (intracellular targeting). 3 types

First order targeting: :

Restricted distribution of the drug carrier system to the capillary bed of the predetermined target site, organ or tissue. Compartmental targeting in lymphatics, peritoneal cavity, plural cavity, cerebral ventricles, lungs, joints, eyes, etc. First order targeting:

Second order targeting: :

The selective delivery of drugs to a specific cell type such as tumour cells (and not to the normal cells) is referred to as second order targeting . Second order targeting:

Third order targeting: :

Drug delivery specifically to the intracellular site of target cells. e.g., receptor based ligand-mediated entry of a drug complex into a cell by endocytosis,lysosomal degradation of carrier followed by release of drug intracellularly or gene delivery to nucleolus. Third order targeting:

Ligand mediated targeting: :

Achieved using specific mechanisms such as receptor dependent uptake of natural LDL particles and synthetic lipid microemulsions of partially reconstituted LDL particles coated with the apoproteins. Ligand mediated targeting:

Physical targeting (Triggered Release) :

The drug delivery programmed and monitored at the external level (ex vivo) with the help of physical means. Temperature sensitive liposomes. Physical targeting (Triggered Release)

4.Dual targeting :

Drug targeting using carrier molecules, having intrinsic antiviral effect thus synergies the antiviral effect of the loaded active drug. Based on this approach, drug conjugates can be prepared with fortified activity profile against the viral replication. 4. Dual targeting

Advantage:

The virus replication process can be attacked at multiple points, excluding the possibilities of resistant viral strain development. Advantage

5.Double targeting: :

In order to achieve a double targeting effect, site specificity of the drug, by virtue of targeting moiety, a high specificity module (mainly a photosensitizer) is linked to antibodies. 5. Double targeting:

6.Combination targeting: :

Suggested by Petit and Gombtz. Site-specific delivery of proteins and peptides. 6. Combination targeting:

Approaches to Drug Targeting:

Physical or Mechanical Approach. Biological Approach. Chemical Approach. Approaches to Drug Targeting

PHYSICAL OR MECHANICAL APPROACH:

Involves formulation of drug using particulate delivery device  physical localization  differential release of drug. Site specificity is due to higher drug concentrations at the site. microspheres, nanoparticles or liposomes. PHYSICAL OR MECHANICAL APPROACH

Targeting to the mononuclear phagocytic system (MPS):

iv administered liposomes—localize within MPS. MPS consists of connective tissues of mesenchymal origin. Functions of MPS : Clearance of large variety of harmful substances from plasma. Catabolism of macromolecules. Participation in immune response. Synthesis and secretion of various effector molecules. Targeting to the mononuclear phagocytic system (MPS)

PowerPoint Presentation:

EXAMPLES: Targeting of azidothymidine (AZT) to macrophages as nanoparticle carriers by iv & oral routes. Liposomal delivery of certain compounds may provide extended retention. Liposomal delivery of drugs systemically enhances drug concentration of antimicrobials.

PowerPoint Presentation:

Targeting to the pulmonary region Liposomes 50 nm in size—retained for many hrs. iv administered microspheres of certain drugs tend to localize in lungs— diagnostic purposes. Extravascular delivery Solid lipid nanoparticles on iv administration accumulate in the brain. E.g.: anticancer drug camptothecin loaded in nanoparticles  increase avg residence time.

Mucosal Delivery of Antigens :

Mucosal surface—main site for pathogenic entry. Production of IgA provide immunity for mucosal surface against many pathogens. Microspheres protect vaccine from acid pH of stomach. Cause induction of IgA Ab in gut mucosa as well as other mucosal surfaces like respiratory & genitourinary tracts. E.g. microspheres of Staphylococcal enterotoxin B toxoid Mucosal Delivery of Antigens

BIOLOGICAL APPROACH:

Involves delivery of the drug using carrier system with targeting moiety either in-built (by virtue of the structure of the carrier) or is chemically coupled. BIOLOGICAL APPROACH

PowerPoint Presentation:

4 approaches: Antibodies directed against specific cell surface antigens, Endogenous carbohydrate-binding proteins ( lectins ) , Glycoconjugates functioning as specific ligands for receptors on specific cells that recognize particular sugar residues, and Hormones functioning as specific ligands for receptors on specific targets.

Antibodies for Antigen Targeting:

Higher immune response—when antigens are directed to antigen presenting cells (APCs) & lymphocytes. Done by coupling antigen with a ligand of strong binding affinity for molecules of MHC. E.g. coupling of viral antigens to monoclonal antibodies against a mouse Class II MHC. Advantage: Preparation of safer vaccines. Targeting without use of carriers. Targeted antigen required only in 1 st injection. Upto 1,000 fold increase in efficiency achieved. Antibodies for Antigen Targeting

Lectins as Targeting Agents:

Endogenous carbohydrate-binding proteins of tumours are known as lectins. Glycoproteins or neoglycoproteins act as carriers  drug incorporated in glycoproteins  carbohydrate on glycoprotein cause its uptake by lectin  drug released intracellularly during proteolysis of carrier. Lectins as Targeting Agents

Low Molecular Weight Proteins for Renal Drug Targeting:

EXAMPLE: Targeting of naproxen using lysozyme as carrier since it is taken up & catabolized in proximal tubules of kidney—Showed 70 fold increase in retention in kidneys compared to free naproxen. Captopril conjugated with lysozymes—6 times more retention in kidneys observed. Polysaccharides such as dextran also show high potential as oral drug carriers. Low Molecular Weight Proteins for Renal Drug Targeting

Hormones Functioning as Specific Ligands for Receptors on the Specific Targets::

Insulin used as enzyme carrier for correcting enzyme deficiency disease in fibroblasts from patients with cholesterol storage disease. Hormones Functioning as Specific Ligands for Receptors on the Specific Targets:

CHEMICAL APPROACH:

Incorporates targeting consideration into the drug design process—for design of safe, localized delivery. Targeting to active biological molecules based on predictable enzymatic activation. Allow sustained release of drugs also. CHEMICAL APPROACH

PowerPoint Presentation:

Drug Targeting to Lung s E.g. ester derivatives of chlorambucil and cromolyn  hydrolyze in lungs rapidly into active parent drugs  enhance delivery and retention time to lung tissue. Drug Targeting to Brain Blood-brain barrier (BBB)  obstruct free flow of blood b/w brain and rest of the body. BBB is impermeable to hydrophilic substances  prevent loss of neurotransmitters to the plasma after synthesis in brain  hence chemical methods are used.

Osteotropic Drug Delivery:

E.g. bisphosphonic (BP) prodrug for 17 β-estradiol (E2)  estrogen replacement therapy in patients of post menopausal oesteoporosis. In rats showed rapid uptake and enhanced halflife of estradiol as compared to free estradiol. Osteotropic Drug Delivery

REFERENCES::

Drug Targeting Organ-Specific Strategies Edited by Grietje Molema and Dirk K. F. Meijer, page no:1-16. Targeted and Controlled drug delivery (Novel carrier systems), S P Vyas and R K Khar , CBS publishers, page no: 38-61. Progress in Controlled and Novel drug delivery systems by N K Jain, CBS publishers, page no: 362-366. REFERENCES:

authorStream Live Help