Ndds unit 3 notes BP701t
Introduction
Targeted drug delivery system Targeted drug delivery systems deliver drugs in the tissues of interest while lowering their relative concentrations in the remaining tissues. In 1906, scientist Ehrlich first proposed the concept of targeted drugs. As an alternative for effective therapeutics, targeted drugs were found to be particularly popular and effective, but the 'magic bullet' has proven difficult to implement clinically as a theoretical idea.
Approaches Ndds unit 1 notes
Drug targeting is the selective and efficient localization of pharmacologically-active moieties at predesigned targets while restricting their access to non-targets. This minimizes toxicity and maximizes the therapeutic index. Drugs are distributed to specific target sites by using a range of research outcomes. The methodology used is broadly divided into three categories: 1. Controlling the distribution of drug by incorporating the drug with a carrier molecule, 2. Using a targeting molecule to direct the drug to a target site, and 3. Using a polyfunctional targeting molecule to direct drugs to their targets.
Two main approaches are
1.passive
2. Active
1. Passive targeting:
• it refers to the accumulation of drug or drug-carrier system at a particular (like in case of a cancerous drug) site whose explanation may be attributed to physicochemical or pharmacological factors of the disease.
• Hence, in case of cancer treatment, the size and surface properties of drug delivery nano-particles (100-nm size) must be controlled specifically to avoid uptake by the reticuloendothelial system (RES), to maximize circulation times and targeting ability.
• For achieving such conditions, the optimal size should be less than 100 nm in diameter and the surface should hydrophilic to circumvent clearance by macrophages (large
phagocytic cells of the RES)
• Other examples include targeting of anti-malarial drugs for treatment of
leishmiansis, brucellosis, candiadsis.
2. Active trageting:
Active targeting includes specific modification of a drug/drug carrier nano systems with
active agents having selective affinity for recognizing and interacting with a specific cell,
tissue or organ in the body.
• in case of cancer, it is achieved by conjugating the nanoparticle to a targeting
component that provides preferential accumulation of nanoparticles in the tumor-
bearing organ, individual cancer cells, intracellular organelles, or specific molecules in cancer
cells.
• Such an approach is based on specific interactions such as lectin-carbohydrate, ligand-
receptor, and antibody-antigen.
• This active targeting approach can be further classified into three different levels of targeting.
Advantages and disadvantage of Tdds
ADVANTAGES
1. Drug administration protocols may be simplified.
2. Toxicity is reduced by delivering a drug to its target site, thereby reducing harmful systemic
effects.
3. Drug can be administered in a smaller dose to produce the desire effect.
4. Avoidance of hepatic first pass metabolism.
5. Enhancement of the absorption of target molecules such as peptides and particulates.
6. Dose is less compared to conventional drug delivery system.
7. No peak and valley plasma concentration.
8. Selective targeting to infections cells that compare to normal cells.
DISADVANTAGES
1. Rapid clearance of targeted systems.
2. Immune reactions against intravenous administered carrier systems.
3. Insufficient localization of targeted systems into tumour cells.
4. Diffusion and redistribution of released drugs.
5. Requires highly sophisticated technology for the formulation.
6. Requires skill for manufacturing storage, administration.
7. Drug deposition at the target site may produce toxicity symptoms.
8. Difficult to maintain stability of dosage form. E.g.: Resealed erythrocytes have to be stored at 4°C.
9. Drug loading is usually low. E.g. As in micelles. Therefore it is difficult to predict/ fix the dosage
regimen.
Liposome:
Greek word, where lipo means “fatty” constitution and soma means “structure”.
• Relatively small in size and it ranges from 50 nm to several micrometres in diameter.
• Spherical vesicle in which aqueous core is entirely enclosed by one or more phospholipid bilayers.
• Unique ability to entrap both lipophilic and hydrophilic compounds.
• The hydrophobic or lipophilic molecules are inserted into the bilayer membrane, whereas
hydrophilic molecules can be entrapped in the aqueous centre.
Advantages:
1. Suitable for delivery of hydrophobic (e.g. amphotericin B) hydrophilic (e.g. cytrabine) and
amphipathic agents.
2. Liposome increases efficacy and therapeutic index of drug (actinomycin-D)
3. Liposome increase stability via encapsulation
4. Suitable for targeted drug delivery
5. Suitable to give localized action in particular tissue
6. Suitable to administer via various routes
7. Liposomes help to reduce the exposure of sensitive tissue to toxic drug.
Disadvantages:
1. Once administrated, liposome cannot be removed.
2. Possibility of dumping, due to faulty administration.
3. Leakage of encapsulated drug during storage.
4. Low solubility
5. Production cost is high.