NANOSYSTEMS - Vesicles, Liposomes, Polymeric micelles & Dendrimers

Explanation about the nanosystems used in Drug delivery

1. INTRODUCTION TO NANOMEDICINE NANOSYSTEMS Vesicles Liposomes Polymeric micelles Dendrimers By Girish Kumar K IV MSc Biomedical Science

2. Nanosystems Nanotechnology to deal with nanoscale objects, has been developed at three major levels Nanomaterials, Nanodevices and NANOSYSTEMS Nanosystems has wide applications in Engineering, Physical Science and Bioscience .

3. VESICLES Drug delivery refers to approaches, formulations, technologies and systems for transporting a pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effect. Currently, vesicles as a carrier system have become the vehicle of choice in drug delivery. Vesicular delivery system provides an efficient method for delivery to the site of infection, leading to reduce of drug toxicity with no adverse effects . Vesicular drug delivery reduces the cost of therapy by improved bioavailability of medication, especially in case of poorly soluble drugs. They can incorporate both by hydrophilic and liophilic drug .

4. Different novel approaches used for delivering the drugs by vesicular system include LIPODIDAL BIOCARRIERS

5. NON-LIPOIDAL BIOCRRIERS

6. Liposomes They are vesicles or bags in which aqueous volume is entirely closed by a membrane composed of lipid(fat) molecules, usually phospholipids . They are bilayered vesicles in which aqueous volume is entirely enclosed by a membranous lipid bilayer that are mainly composed of natural or synthetic phospholipids. These vesicles can encapsulate water soluble drugs in their aqueous spaces and lipid soluble drug within the membrane itself.

7. Mechanism of Liposome formation To understand why liposome are formed when phospholipids are hydrated it is needed to understand basic physiochemical features of phospholipids. Phospholipids are amphipathic molecules which have affinity for both aqueous and polar moieties as they have hydrophobic tail and is composed of two fatty acids containing 10-24 carbon atoms 0-6 double bonds in each chain. In aqueous medium the phospholipid molecules are oriented in such a way that the polar portion of the molecule remains in contact with the polar environment and at the same shield the non polar part.

8. They align themselves closely in planer bilayer sheets to minimize the interaction between the bulky aqueous phase and long hydrocarbon fatty acyl chains. This alignment requires input of sufficient amount of energy (shaking, sonication, homogenization, heating etc.) Interactions are completely eliminated when these sheets fold over themselves to form closed, sealed and continuous bilayer vesicles.

9. Classification Multilamellar vesicles (MLVs) – several bilayers and size ranging from 100nm to 20m. Small unilamellar vesicles (SUVs) – composed of single lipid bilayer with diameter ranging from 20-100nm. Large unilamellar vesicles (LUVs) – consist of single bilayer with diameter ranging from 0.1-1m. Multivesicular vesicles (MVVs) – consists of vesicles with size ranging from 100nm-20m.

10. Therapeutic application Liposomes are used as drug /protein delivery vehicles Enhances drug solubilisation Enzymal replacement therapy and lysosomal storage disorder Used in antifungal, antiviral, antimicrobial and tumour therapy.

11. Advantage Provide selective passage targeting to tumour tissues . Increased efficacy and therapeutic index. Increased stability via encapsulation. Reduction in toxicity of encapsulated agent. Improved pharmacokinetic effect. Used as carrier for controlled and sustained drug delivery. Can be made into variety of sizes .

12. Disadvantage Leakage of encapsulated drug during storage. Uptake of liposomes by the reticuloendothelial system. Batch to batch variation . Once administrated cannot be removed.

13. Another type of drug delivery vehicle used is polymeric micelles . These are spherical in shape and are formed by single chain lipids. A micelle is aggregate of surfactant molecules dispersed in a liquid colloidal. In a micelle, the hydrophobic tails of several surfactant molecule assemble into an oil-like core. Polymeric micelles

14. Polymeric micelles Miceller systems for systemic delivery of insoluble drugs. Amphiphilic copolymer self associate to form micelles in water. Small size <100nm in diameter leads to avoiding of renal excretion and RES. Small size also leads to increase endothelial cell permeability . Accumulate gently into tumour cell than the normal.

15. Amphiphilic block copolymers that self assemble to form a micelle with hydrophobic core and a hydrophilic shell . The drugs can be attached to shell or encapsulated within the core.

16. Advantage It can carry water insoluble drugs . It is biocompatible . It is biodegradable . Can be easily modified and functionalized.

17. Disadvantage It is more difficult to selectively target the cancer cells . Optimal concentration must first be determine for micelle form.

18. Dendrimers Dendritic materials comprises sub classes such as Dendrimers Dendron Hyperbranched polymers Dendrigraft polymers Dendronized polymers

19. Dendrimers are polymer-based drug delivery vehicles. They have a core that branches out in regular intervals to form a spherical , small and a very dense narrow carrier. Dendrimers are highly branched, three dimensional feature the resembles architect of a tree. Dendrimers

20. Two strategies are used for the application of dendrimers to the drug delivery 1. Drug encapsulation by dendritic structure 2. Drug conjugation to dendrimers Firstly , the drug molecules can be physically entrapped inside the dendrimers. Secondly , the drug molecules can be covalently attached onto surface or other functional group. Various functional moieties based on dendrimers provide miscellaneous biomedical applications of these promising materials, such as cancer targeting therapy .

21. There are different types of Dendrimers Pamam dendrimers – Poly (amidoamine) dendrimes posses amino groups on the surface. Pamamos dendrimers – Inverted unimolecular micelles consists of hydrophilic nucleophilic PAMAM interiors and hydrophobic organosillicon (OS) exterior. PPI Dendrimers – Poly alkyl amines having primary amines as end groups and its interior consists of numerous tertiary trispropylene amine. Tecto dendrimer – Composed of core dendrimer with multiple dendrimers at its periphery.

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