Introduction to Niosomes.

 

Introduction.

• Niosomes are a novel drug delivery system that encapsulates the medication in a vesicular system made up of non ionic surfactants. 

• The vesicle is made up of a bilayer of non-ionic surfactants, thus the name niosomes.

• Niosomes are extremely small and microscopic (on a nanometric scale). 

• Despite having a similar structure to liposomes, they have several advantages over them. 

Advantages of Niosomes.

1. The vesicles may act as a depot, releasing the drug in a controlled manner. 

2. They are osmotically active and stable, and also they increase the stability of entrapped drugs. 

3. They improve the therapeutic performance of the drug molecules by delayed clearance from the circulation, protecting the drug from biological environment and restricting effects to target cells. 

4. The surfactants used are biodegradable, biocompatible and nonimmunogenic. 

5. They improve oral bioavailability of poorly absorbed drugs and enhance skin penetration of drugs. 

6. They can be made to reach the site of action by oral, parenteral as well as topical routes. 

7. Handling and storage of surfactants requires no special conditions. 

8. Due to the unique infrastructure consisting of hydrophilic, amphiphilic, and lipophilic moieties together, they, as a result, can accommodate drug molecules with a wide range of solubilities. 

9. Niosomal dispersion in an aqueous phase can be emulsified in a non-aqueous phase thus regulating the delivery rate of the drug and administering a normal vesicle in an external non-aqueous phase. 

Disadvantages of Niosomes.

1. Physical instability of the noisome vesicles is a major disadvantage of the niosomal drug delivery system. 

1. Aggregation: Aggregation of the niosome vesicles can be another disadvantage to be considered. 

2. Fusion: Fusion of the niosomal vesicles to form loose aggregates or to fuse into larger vesicles will affect the uniformity of the size of the noisome vesicles. 

2. Leaking of entrapped drugs: leakage of the entrapped drugs from the polymer system will affect the intended properties of the niosomes. 

3. Hydrolysis of encapsulated drugs which limit the shelf life of the dispersion.

Types Of Niosomes: 

• The niosomes are classified as a function of the number of bilayers (e.g. MLV, SUV) or as a function of size. (E.g. LUV, SUV) or as a function of the method of preparation (e.g. REV, DRV). 

1. Multilamellar vesicles (MLV):

1. It consists of a number of bilayer surrounding the aqueous lipid compartment separately. 

2. The approximate size of these vesicles is 0.5-10 µm diameter. 

3. Multilamellar vesicles are the most widely used niosomes.

4. These vesicles are highly suited as drug carriers for lipophilic compounds.

2. Large unilamellar vesicles (LUV):

1. Niosomes of this type have a high aqueous/lipid compartment ratio, so that larger volumes of bio-active materials can be entrapped with a very economical use of membrane lipids. 

3. Small unilamellar vesicles (SUV):

1. These small unilamellar vesicles are mostly prepared from multilamellar vesicles by the sonication method, French press extrusion.

Applications of Niosomes:

1. Niosomes are often used for target drugs to the reticulo-endothelial system.

2. Niosomes can also be utilized for targeting drugs to organs other than the RES. A carrier system (such as antibodies) can be attached to niosomes to target them to specific organs.

3. Antineoplastic Treatment: 

1. Most antineoplastic drugs cause severe side effects. Niosomes can alter the metabolism, prolong circulation and half-life of the drug, thus decreasing the side effects of the drugs. 

4. In diagnostic imaging with a carrier containing radio pharmaceutics.

5. In treatment of Leishmaniasis, where the drugs of choice are antimony derivatives which are well known for their side effects, entrapping them inside the niosomes can minimize the side effects.

6. Can be used to improve absorption of the poorly absorbed peptides like vasopressin.

7. Niosomes can be used as carriers for hemoglobin within the blood. 

8. The niosomal vesicle is permeable to oxygen and hence can act as a carrier for hemoglobin to anemic patients. 

Commonly Asked Question.

1. Write a short note on “Niosomes”.

Introduction to Liposomes.

 

Introduction.

• Liposome was first discovered in the early 1965 by Alec D. Bangham.

• Liposome word is derived from two Greek words,

• Lipo: Fatty. + Soma: Body= Hence literally it means a lipid body. 

• They are relatively small in size and it ranges from 50 nm to several micrometers in diameter. 

• They are spherical vesicles in which an aqueous core is entirely enclosed by one or more phospholipid bilayers. 

• It has the 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 center. 

• Because of their biocompatibility, biodegradability, low toxicity, and aptitude to trap both hydrophilic and lipophilic drugs they simplify site-specific drug delivery to tumor tissues, being so versatile they have emerged as a prominent Targeted drug delivery system.

ADVANTAGES OF LIPOSOMES.

• Hydrophobic (e.g., amphotericin B), hydrophilic (e.g., cytarabine), and amphipathic agents can be delivered. 

• Liposomes improve drug efficacy and therapeutic index (actinomycin-D). 

• Liposomes improve stability through encapsulation of the drugs. 

• Appropriate for targeted drug delivery. 

• Suitable for providing localized action in a specific tissue 

• Suitable for administration via a variety of routes 

• Liposomes aid in reducing toxic drug exposure to sensitive tissue. 

DISADVANTAGES OF LIPOSOMES.

1. Liposomes cannot be removed once they have been administered. 

2. Dumping is a possibility as a result of poor administration. 

3. Encapsulated drug leakage during storage 

4. Solubility is low. 

5. The cost of production is high.

CLASSIFICATION OF THE LIPOSOMES:

• Depending on various criteria they are classified as follows,

• Based on structural parameters.

• Based on method of preparation: 

• Based on composition and application.

1. Based on structural parameters:

1. MLV: 

• multilamellar large vesicles .0.5 µm. 

• They have several bilayer 

2. OLV: 

• oligo lamellar vesicles 0.1-1µm. 

• Made up of 2-10 bilayer of lipids surrounding a large internal volume. 

3. UV: 

• unilamellar vesicles (all size range) 

4. SUV: 

• Small unilamellar vesicle composed of single lipid bilayer with diameter ranging from 30-70 nm.

5. MUV: 

• Medium unilamellar vesicle

2. Based on composition and application:

1. Conventional Liposomes (CL): 

• Neutral or negatively charged phospholipid and cholesterol 

2. Fusogenic Liposomes (RSVE): 

• Reconstituted Sendai virus envelopes 

3. pH sensitive Liposomes: 

• Phospholipid such as PE or DOPE with either CHEMS or OA 

4. Cationic Liposomes: Cationic lipids with DOPE 

5. Long Circulatory (Stealth) Liposomes (LCL): 

• Liposome that persist for prolong period of time in the bloodstream 

6. Immuno-Liposomes: 

• Immune liposomes have specific antibodies on their surface to enhance target site binding.

3. Based on method of preparation:

1. REV: single or oligo lamellar vesicles made by reverse phase evaporation method 

2. MLV-REV: multilamellar vesicle made by reverse phase evaporation method 

3. SPLV: stable pluri lamellar vesicle 

4. FATMLV: Frozen and thawed MLV 

5. VET: vesicle prepared by extraction method 

6. DRV: dehydration-rehydration method

PREPARATION OF LIPOSOMES:

• There are many ways of preparing liposomes. Some of the important methods are as follows,

1. Hydration of lipids in presence of solvent 

2. Ultrasonication 

3. French Pressure cell 

4. Solvent injection method

1. Ether injection method 

2. Ethanol injection

5. Detergent removal Detergent can be removed by 

1. Dialysis 

2. Column chromatography 

3. Bio-beads

6. Reverse phase evaporation technique 

7. High pressure extrusion 

8. Miscellaneous methods 

1. Removal of Chaotropic ion 

2. Freeze-Thawing.

Characterization OF liposomes:

• It can be done by following three ways,

1. Physical characterisation: evaluates parameters including size, Shape, surface features, lamellarity, phase behavior and drug release profile. 

2. Chemical characterisation: includes those studies which establish the purity, potency of various lipophilic constituents. 

3. Biological characterisation: establishes the safety and suitability of formulation for therapeutic application. 

Applications of Liposomes:

1. Cancer chemotherapy: 

• Liposomes have been used successfully to entrap anticancer drugs. 

• This prolongs circulation lifetime and protects against metabolic degradation. 

2. Liposome as carrier of drug in oral treatment: 

• Steroids used to treat arthritis can be incorporated into large MLVs. 

• Oral administration of liposome-encapsulated insulin altered blood glucose levels in diabetic animals. 

3. Liposome for topical application: 

• Triamcinolone, methotrexate, benzocaine, corticosteroids, and other drugs can be successfully incorporated as a topical liposome. 

4. Liposome for pulmonary delivery: 

• Inhalation devices like nebulizers are used to produce an aerosol of droplets containing liposomes.

Commonly asked Question.

1. Write in detail about Liposomes.

Strategies of Drug Targeting.

 

Introduction.

• Targeting drugs to specific cells and tissues of the body without allowing them to enter the systemic circulation is an innovative concept. 

• The drug can be given in such a way that it reaches the receptor site in sufficient concentration without disrupting an extraneous tissue cell.  

• These products are created by taking into account:

• Specific properties of the target cells.

• Nature of markers or transport carriers or vehicles which convey drugs to specific receptors.

• Ligands and physically modulated compounds. 

Important Properties Influencing Drug Targeting:

• The general properties influencing drug targeting can be divided into three broad categories, such as drug, carrier, and in vivo environment properties.

1. Drug:

1. Concentration, 

2. Particulate location and Distribution 

3. Molecular Weight, 

4. Physicochemical properties 

5. Drug Carrier Interaction.

2. Carrier:

1. Type and Amount of Excipients 

2. Surface Characteristics, 

3. Size 

4. Density

3. In vivo environment properties:

1. pH, 

2. Polarity, 

3. ionic strength, 

4. Surface Tension, 

5. Viscosity, 

6. Temperature, 

7. Enzymes

8. Electric Field

Strategies of Drug Targeting:

• Different approaches are being identified and used successfully for the drug targeting, they are as follows.

• Passive Targeting.

• Inverse Targeting.

• Active Targeting.

• First Order Targeting.

• Second Order Targeting.

• Third Order Targeting.

• Ligand Targeting.

• Physical Targeting.

• Dual Targeting.

• Double TArgeting.

• Combination Targeting.

1. Passive Targeting:

• This refers to the carrier's natural in-vivo distribution pattern. 

• The particle size, shape, surface characteristics, surface charge, and particle number all play a role in the carrier's disposition.

• For example, the ability of some colloids to be taken up by the ReticuloEndothelial Systems (RES), particularly in the liver and spleen, made them ideal substrates for passive hepatic drug targeting. 

2. Inverse Targeting:

• This type of targeting attempts to avoid passive uptake of colloidal carriers by RES; thus, the process is known as inverse targeting. 

• To achieve inverse targeting, the normal function of the RES is suppressed by injecting large amounts of blank colloidal carriers or macromolecules such as dextran sulfate prior to injection.  

• This strategy results in RES saturation and suppression of defense mechanisms. 

• This type of targeting is an effective method for delivering drugs to non-RES organs.

3.  Active Targeting:

•  In this approach the carrier system bearing drug reaches a specific site on the basis of modification made on its surface rather than natural uptake by RES. 

• Surface modification techniques include coating of surface with either a bioadhesive, non-ionic surfactant or specific cell or tissue antibodies (i.e. monoclonal antibodies) or by albumin protein. 

• Active targeting can be affected at different levels:

• First order targeting (organ compartmentalization) - Restricted distribution of the drug carrier system to an organ or tissue. 

• Second order targeting (cellular targeting) - The selective drug delivery to a specific cell type such as tumor cells (& not to the normal cells)

• Third order targeting (intracellular organelles targeting) - Drug delivery specifically to the intracellular organelles of the target cells 

4. Ligand-mediated Targeting:

• In this approach ligands are attached to the carrier surface as group(s), which can selectively direct the carrier to the pre-specified site(s). 

• Most carrier systems are colloidal in nature and can be specifically functionalized with a variety of biologically relevant molecular ligands such as antibodies, polypeptides, oligosaccharides, viral proteins, and fusogenic residues. 

• The ligands provide recognition and specificity on the drug carrier, allowing them to approach the respective target selectivity and deliver the drug. 

• e.g. 

• Folate---> Folate receptor----> Overexpression of folate receptor.

• Galactosamine---> Galactosamine receptors on hepatocytes---> Hepatoma.

5. Physical Targeting: 

•  This approach was found exceptional for tumor targeting as well as cytosolic delivery of entrapped drugs or genetic material. 

• Characteristics of environment changes like pH, temperature, light intensity, electric field, and ionic strength are used for targeting the specific organ sites for delivering the drug molecules.

• 

6. Dual Targeting:

• Carrier molecules have their own therapeutic activity in this targeting approach, which increases the therapeutic effect of the drug. 

• For example, a carrier molecule with antibacterial activity can be loaded with an antibacterial drug, and the drug complex's net synergistic effect was observed. 

7. Double Targeting:

• When temporal and spatial methodologies are used to target a carrier system, this is referred to as double targeting. 

• Spatial placement refers to targeting drugs to specific organs, tissues, cells, or even subcellular compartments, whereas temporal delivery refers to controlling the rate of drug delivery to the target site. 

8. Combination Targeting: 

• These targeting systems are outfitted with carriers, polymers, and molecularly specific homing devices that could provide a direct approach to the target site. 

Advantages of Drug Targeting:

1. Protocols for drug administration could be made simpler.  

2. Delivering a drug to its intended site reduces toxicity by minimizing negative systemic effects. 

3. A smaller dose of the drug can be used to achieve the desired effect. 

4. Avoidance of hepatic first pass metabolism. 

5. Improved absorption of target molecules like peptides and particles. 

6. Compared to traditional drug delivery methods, the dose is lower. 

7. No peak and valley plasma concentration. 

8. selectively focusing on infected cells in comparison to healthy cells 

Disadvantages of Drug Targeting.

1. Targeted systems are quickly cleared. 

2. Immune responses to carrier systems administered intravenously. 

3. Targeted systems are not fully localized inside tumor cells. 

4. Redistribution and diffusion of released drugs 

5. High-end technology is needed for the formulation. 

6. Skill for manufacturing, storage, and administration is needed. 

7. At the target site, drug deposition could result in toxicological symptoms. 

8. Maintaining dosage form stability can be challenging. For instance, erythrocytes that have been resealed must be kept at 4°C. 

9. Since drug loading is typically legal, such as in micelles, it is challenging to foresee or fix the dosage regimen. 

Commonly Asked Questions.

1. Discuss different strategies / approaches used for drug targeting. Give advantages and disadvantages of Drug Targeting.