Fundamental Nanoscience (Lectures 1-3) PDF

# Fundamental of Nanoscience & Nanotechnology (NT111) ## **Course Grading** | Type | Degree % | |---|---| | Midterm Exam | 20% | | Final Exam | 60% | | Work assignment + class room activities | 10% | | Project | 10% | ## **Richard Feynman** December 29, 1959 Nobel Prize Winner Richard Feynman on nanotechnology at the physics national conference (AIP): "There's Plenty of Room at the Bottom" ## **How big is a Nanometre?** - It is a millionth of a millimetre (10^-6 mm) - or a billionth of a metre (10^-9 m) ## **The scale of things** ### **Things Natural** | | Size | |---|---| | Ant | 5 mm | | Dust mite | 200 μm | | Human hair | 60-120 μm | | Fly ash | 10-20 μm | | Red blood cells | 2-5 μm | | ATP synthase | 10 nm | | DNA | 0.5-2 nm | | Atoms of silicon | 10-10 m | | Spacing | 0.078 nm | ### **Things Manmade** | | Size | |---|---| | Head of a pin | 1-2 mm | | Microwave | 0.1 mm | | MicroElectro Mechanical (MEMS) devices | 10-100 μm | | Zone plate x-ray "lens" | 35 nm | | Quantum 48 Fe+2 atoms | 14 nm | | Carbon nanotube | 1.3 nm | | Carbon buckyball | 1 nm | ## **What is nanotechnology?** - Development of materials & devices by exploiting characteristics of particles on nano-scale (by humans). ## **Why nano?** - At nanoscale, strange things happen to materials properties. ## **Material Properties** | Material Properties | Example | |---|---| | Reactivity | Which dissolves faster in water Granulated sugar or Sugar Cubes? Granulated sugar dissolves faster than sugar cubes due to its smaller particle size, providing more surface area for quicker interaction with water. | | Size | Which of these is Gold? Colour of gold can range from purple to red depending on size of atom clusters. | | Magnetism | Superparamagnetic iron oxide in magnetic resonance imaging MRI when exposed to a magnetic field, enhance imaging contrast, making them valuable tools in medical diagnostics. | ## **Basic Approaches for Synthesis of Nanoparticles** ### **Bottom-up** - Assemble from Nano-building blocks - Powder/aerosol compaction - Chemical synthesis ### **Top-down** - Sculpt from Bulk - Mechanical attrition - Lithography - Etching ## **Fragment Bulk** - It starts with atoms or molecules to make clusters then build up to nanostructures. - Fabrication is much less expensive. - It produces nanoparticles with defined size and structure. ## **Biological Method** - Using plant and their extracts - Using microorganisms (bacteria, fungi and actinomycetes) - Using algae (micro-seaweeds) - Using enzymes and biomolecules - Using industrial and agricultural wastes ## **Chemical method** - Coprecipitation method - Chemical reduction of metal salts - Electrochemical method (electrolysis) - Microemulsion method - Pyrolysis - Phytochemical (irradiation) method - Sonochemical method - Sol-gel process - Solvothermal Synthesis ## **Physical method** - Arc discharge method - Electron beam lithography - Ion implantation - Inert gear condensation - Mechanical grinding - Milling - Spray pyrolysis - Vapour-phase synthesis ## **Beyond Bioinspired Materials?** - Can we engineer biological cells to produce materials of our interest? ## **Engineered Living Materials (ELMs)** "ELMs are living cells that form or assemble the material itself, or modulate the functional performance of the material" ## **Living Cells are utilized as Factories to produce Functional Materials** | **Engineered** | **Living** | **Materials** | |---|---|---| | Genetic Modification | Cell as a Biofactory | Structural Materials | | Mechanical Control of Bulk Structure | Self-healing Materials | Biohybrid Devices | | Chemical Functionalization | Dynamic Response | Biocatalytic Materials | | Biotemplating | Self-growing Materials | Biosorptive Materials | ## **Biofilms** - A biofilm is an assemblage of surface-associated microbial cells that is enclosed in an extracellular polymeric substance matrix. ### **Examples:** * **E. coli: Curli Biofilms** - Biofilms, communities of bacteria that live together for the benefit of the group, are characterized by: * Water channels * Complex 3-dimensional structures * Increased resistance to environmental stresses - Curli fibers are one of major components of extracellular matrix in E. coli biofilms, & it's important for biofilm development. ## **Engineering Biofilm Matrix Using BIND Technology** - BIND is an approach that operates within framework of curli biofilms, and targeting curli system to produce functional nanofibers. - It's a versatile nanobiotechnological platform for developing robust materials with programmable functions. ### **Definition:** * **BIND (Biofilm-Integrated Nanofiber Display)** - It's molecular programming of bacterial extracellular matrix material by genetically modifies CsgA (amyloid protein) in bacterial biofilms, causing secretion of engineered fusion proteins that autonomously assemble into functional (amyloid) nanofiber networks (meshwork) within biofilm matrix (E.coli biofilms). ### **Application:** 1. Heavy Metal Removal from Water 2. Pollutant Degradation 3. Waste Treatment 4. Bioremediation 5. Air Quality Improvement 6. Precious Metal Recovery ## **Classification of Nanomaterials According to Dimensions** | **Dimension** | **Description** | **Example** | |---|---|---| | **Zero- Dimensional** | (No extended geometries or surfaces) (Concentration of mass or properties at a single point 0) 3 dimensions at nanoscale (x, y, z) No dimensions greater than 100nm Confined in all directions with no distinction between length, width, and height. Includes nanospheres & nanoclusters Nanoparticles such as quantum dots. | Fullerenes | | **One- Dimensional** | (Linear structures with extension along one dimension) 2 dimensions at nanoscale (x, y), Other outside nanoscale Confined in two directions with one dimension at nanoscale Leads to needle shaped nanomaterials Include nanofibers, nanotubes, Nanowires, nanorods Allow for directed charge transport. | Carbon Nanotubes | | **Two- Dimensional** | (Flat surfaces or structures with extension in two dimensions) 1 dimensions at nanoscale (x) Other outside nanoscale Confined in one direction (thickness) with two dimensions at nanoscale. It's platelike shapes nanofilms, nanolayers and nanocoatings with nanometre thickness | Graphene Molybdenum Disulfide | | **Three- Dimensional** | (Structures that extend in all three dimensions, forming objects with full geometric extension No dimensional constraints. 3 dimensions above 100 nm (Out of nanoscale) Not confined to the nanoscale in any dimension | Porous Materials Scaffolds for Tissue Engineering | ## **Fullerenes (3 Dimensions Nanoscale)** - **Nobel Prize (1996):** Kroto, Smalley, & Curl awarded for discovering fullerene. - **Unique Structure:** Fullerene has a sp2 carbon structure, forming highly symmetric cages of various sizes (e.g., C60, C76). - **Abundance:** C60 is the most abundant fullerene in synthesized compositions. - **Exceptional Hardness:** Hardness of C60 exceeds stainless steel & diamond. - **Solid Phase Structure:** C60 has a face-centered cubic lattice (FCC) in solid phase. - **High Stability:** Fullerene's cage remains stable below 1000°C. - **Photodynamic Therapy "PDT” (Antioxidant):** - C60, when exposed to visible light, generates oxygen species - We need to calculate all input to avoid hyperthermia (Mechanism Below). - **Outstanding electron acceptor properties:** help electrons to travel up to several centimeters from the point where they're knocked loose by a photon. (In organic cells, electrons can travel only a few hundred nanometers or less) ### **Applications:** 1. Antiviral and AntiHIV activity 2. Biosensors 3. Cancer treatment and PDT 4. Drug Delivery Systems 5. Antioxidant and Radical scavenging ## **Graphene (2 Dimensions Nanoscale)** - **Structure:** unique 2-dimensional structure and exceptional physicochemical properties with only one-atom-thick sp2-bonded carbon layer. - **Discovery:** Of Electrical properties in 2004. ### **Properties:** - Excellent thermal conductivity. - Exceptional mechanical strength/weight ratio. - High specific surface area (2620 m2.g-1). ### **Graphene Oxide (GO):** - High surface area. - Abundance of surface functional groups. - Low density compared to other substances like clays & oxides. ### **Graphene Characteristics:** - **Electronic Properties:** - High electron mobility at room temp. (>15,000 cm2/Vs). - Semi-metal or zero-gap semiconductor. - Low resistivity with superior current capacity and temperature conductivity. - Estimated operation at terahertz frequencies (trillions of operations / sec.) - **Optical Properties:** - Unexpectedly high opacity for an atomic monolayer. - Absorbs 2.3% of white light (α: Fine-structure constant). - Saturates readily under strong excitation over visible to near-infrared region due to universal optical absorption. - **Mechanical Properties:** - Strongest material ever tested. - Breaking strength 200 times greater than steel. - Bulk strength of 130 GPa* (*GPa: Gigapascal, Pressure Unit) ## **Electrons Confinement** | **Nanomaterials** | **Electron Status** | |---|---| | 0-D | Electrons are Fully Confined | | 1-D | Electron Confinement & Delocalization Coexists | | 2-D | Electrons are Fully Delocalized | | 3-D | Electrons are Fully Delocalized | - Effect of confinement on resulting energy calculated by quantum mechanics, as the "particle in the box" problem. - An electron is considered to exist inside of an infinitely deep potential well (region of -ve energies), from it can't escape and is confined by dimensions of nanostructure. ## **Classification of Nanomaterials According to their Classes** ### **Inorganic** | **Metals** | **Non-metals** | **Polymers** | **Lipids** | **Carbon Structures** | |---|---|---|---|---| | Noble | Mesoporous Magnetic Silica | Nanosphere | Micelle | Graphene | | Magnetic | Hollow Mesoporous Silica | Nanocapsule | Liposome | Fullerene | | Oxide | | Dendrimer | | | | Quantum Dots | | | | Nanotube Carbon Dots | ## **Quantum Dots (Metals – Inorganic – Nanomaterials)** - **What are Quantum Dots (QDs)?** - Heterogeneous class of engineered nanoparticles that are both semiconductor and fluorophore. - **QD Structure** - Nanocrystal - Semiconducting core - Shell of 2nd semiconductor material - Diameter from 2-10 nm - **Examples:** (Si, Ge, CdS, CdSe, CdTe, ZnSe, PbS, PbSe, InP, InAs) - **Properties of QDs:** - High brightness due to the extinction coefficient - Broad absorption characteristics and a narrow band width in emission spectra - Longer fluorescence lifetime ranging from 10 - 40 ns compared to the organic dyes. - So, it's used at CT as it's safely eliminated from by kidney. - **Applications of QDs:** - Computing: Increase performance and storage of computers - Biology: Cell labelling, cancer therapy, & lymphocyte immunology - Light Emitting Devices (LED): displays industry - Photovoltaic devices: ↑ Efficiency & Cost of Silicon Photovoltaic cells. - Security Tags: can be detected using night-vision goggles - **Disadvantages of QDs:** - May be toxic according to its composition (includes heavy metals) - Unknown degradation specially inside the living organism. - Due to its small size, it may pass the Blood-Brain Barrier (BBB), potentially leading to cytotoxicity. ## **Magnetic Nanoparticles (Metals – Inorganic – Nanomaterials)** - **What are - Magnetic nanoparticles?** - Definition - Are nanomaterials with a distinct magnetic core, consisting of essential elements such as iron, nickel, cobalt, chromium, manganese, gadolinium, and their chemical compounds. - **Characteristics:** - Superparamagnetic due to its nanoscale size, that offering great potential in various applications, available in: - Bare Form - Coated with a Surface Coating - Tailored with functional groups chosen for specific uses. - **Applications of Magnetic Nanoparticle:** - Information Storage - Bio-Separation - Bio-Sensor - Molecular Imaging - Catalysis - Cancer Therapy - **Superparamagnetism** - Characteristic by small ferromagnetic or ferrimagnetic nanoparticles. - At nanoscale, these particles can undergo random magnetic orientation changes due to thermal fluctuations. - In absence of an external magnetic field, nanoparticles exhibit continuous oscillation in all directions. - When subjected to a magnetic field, they align in same direction & guided towards target tissues, such as tumor cells, applying slight temp. ↑induces an oscillation field, contributing to targeted therapy by causing localized effects & potential tumor cell destruction. ## **Noble Metals Nanoparticles (Metals – Inorganic – Nanomaterials)** - **What are Nobel Magnetic nanoparticles?** - Definition - Nanoparticles composed of noble metals, such as ruthenium, rhodium, palladium, silver, osmium, iridium, platinum & gold. - **Characteristics:** - Exceptional resistance to corrosion & oxidation, at High Temp. - **Properties:** - Unique electronic, optical, and catalytic properties due to their nanoscale dimensions. - **Applications:** - In Medical diagnostics - Gene Delivery Detection - Targeting Diagnostics Detection - Drug Delivery Detection - Intracellular-trafficking Targeting - Biosensing Targeting ## **Classification of Porous Materials (Non-Metal – Inorganic – Nanomaterials)** | **Classification** | **Description** | **Example** | |---|---|---| | **Depending On Pore Size** | They differ in radius, which affects functions and applications | Microporous: “<2nm ZSM-5” Mesoporous: “2-50 nm MCM-41” Macroporous: “>50nm Sponge” | | **Depending On Building Framework** | | Purely Inorganic Silica Organic Inorganic Hybrid (MOF) Purely Organic (Organic Porous Polymers) | ### **What are Porous Materials?** - Porous Materials are continuous and solid network material filled through voids. - Material can be recognized as porous if its internal voids can be filled with gases. - Usually synthesized by use of soft template Method (MCM) ### **Properties of Mesoporous Materials:** - Surface area 400-1000 m2/g - Large pore Volume - High stability 500 - 600 ### **Applications of Mesoporous Materials:** 1. Environment field (adsorbents, catalysts) 2. Biomedical field (drug delivery, bone regeneration) 3. Chemical catalysis (catalysts, supports) 4. Nanomaterials preparation (nanoparticles, nanoarray) 5. Functional devices (sensors, solar cells) ## **Synthesis of Mesoporous Materials Using Soft Template Strategy?** 1. Surfactants 2. Formation of Micelles 3. Inorganic precursor 4. Interaction of Micelles with inorganic precursor 5. Hydrothermal treatment followed by separation and drying 6. Removal of template ## **Complete Synthesis Summary** ## **Stepwise formation of mesoporous SiO2 material** ## **Surfactants** - Large organic molecules(High molecular weight) that lower the surface tension between two substances. - Consisting of: - Hydrophilic (polar) water loving head) - Hydrophobic (Non polar, water hating tail) - Regions - Used to stabilize emulsions & facilitate formation of micelles. - Classified According to charge into: - Cationic (+): “Toxic & Expensive" - High critical Micelle con., acidic & basic media - Anionic (-): - Repulsion between anionic surfactant is more. - Neutral (): “non-toxic and cheap" - High critical micelle temp, acidic & basic media - Amphoteric (+, -) ## **Formation of Micelles** - At a Low surfactant conc. will favor arrangement on surface. - ↑Conc. surface become crowded → molecule arrange in to micelles. (Low micelle Conc. ➔ good arrangement) - At certain conc. (CMC) surface is completely loaded then Micelle arranged. “Critical Micelle Concentration” - Self-assembly of micelle occurs to from 3D & 2D rod like arrays ## **Inorganic Precursor (Silica)** - Basic Synthesis (pH= 9.5 to 12.5) - Polymerization of silicate species are reversible (Silica gel, colloidal sol, Water glass, TEOS etc.) - Acidic synthesis(pH= 1 to 2) - Irreversible, Slow hydrolysis TEOS is preferred ## **Interaction of Micelles with Inorganic Precursor** - Direct or intermediate Interaction occurs - Providing a template of hybrid nanostructured materials - Interaction occurs at Basic-Medium or Acidic Medium. - Improve mesoscopic regularities of products. - Reorganization, growth and crystallization - 80-150 °C is temperature is usually used. ## **Hydrothermal Treatment Why Needed?** - High temperature ➔ disorder & decomposition of micelle. ## **Separation and Drying** - Separation - filtration or centrifugation. - Washing (alcohol or water) then Drying at room temp. ## **Removal of Template** - Removal of template will give rise to mesoporosity - Template can be removed by: - Calcination: Slow heating rate, not good for low thermal stable material (350° – 550°), can't reuse surfactant - Solvent Extraction: by ethanol /THF, reused of surfactant - Light irradiation: by Ultra Violet rays or Microwave ## **Dendrimers (Polymers – organic – Nanomaterials)** - **What are Dendrimers?** - It's new class of polymeric materials, having highly branched macromolecules with nanometer-scale dimensions. - Dendrimer Surface possess numerous chain, that modified to perform specific chemical functions. - They're Synthetic 3-dimensional hyper branched, globular macromolecule, characterized by highly branched 3D structure that provides a high degree of surface functionality. - Dendrimers are artificial macromolecules that exhibit a highly branched and monodisperse structure. - **The Dendritic Structure (Possess 3 components)** - Core: (Initiator) - Interior: (Generations) Repeated units, radically attached to the core. - Surface: (Exterior) It's Terminal Functionality, & attached to interior. ## **Factors Affecting Dendrimers:** | **Factor** | **Effect on Dendrimers** | |---|---| | Intrinsic viscosity | ↑ Intrinsic viscosity →↑ Dendrimer generation Due to larger size and more branches affecting hydrodynamic volume | | Solvent Quality (Polarity) | Collapse of Dendrimer Structure (Back folding) occurs in Poor Solvents. Due to unfavorable interactions with the solvent At Good Solvent, solubility and stability of Dendrimer Enhanced (extended conformation). | | Effect of pH | Higher pH may ↑ dendrimer charge & stability. | | Effect of Salt Ionic strength or Salt Concentration | Higher salt conc. → Collapse of dendrimer Due to screening of electrostatic repulsion between surface groups | | Effect of Concentration | ↑ Intermolecular crowding → dendrimer collapse or expanded coil dimension depending on generation/functionality | | Biological Effects Cytotoxicity | Cytotoxicity with higher polymer generations Due to greater interaction with cell membranes through higher multivalency or ionization | ## **Applications of Dendrimers** ### **Pharmaceutical Applications** 1. Dendrimers As Nano-Drugs 2. Dendrimer As Solubility Enhancers 3. Gene Therapy 4. Photodynamic Therapy 5. Tissue Engineering 6. Gene Transfection 7. Boron Neutron Capture Therapy 8. Targeted And Controlled Release Drug Delivery - Delivery of Anticancer Drugs 9. Cellular Delivery Using Dendrimer Carriers 10. Cardiac Testing 11. Drug and Gene Delivery - Drug Delivery - Gene Delivery - Advancement in Gene Therapy ### **Non-Pharmaceutical Application** 1. Diagnostics-MRI 2. Industrial Processes 3. Dendritic Catalysts / Enzymes - Metallodendritic catalysts - Catalysis with phosphine-based dendrimers - Catalysis with (metallo) dendrimers containing chiral ligands - Non-metal containing dendrimers ## **Mechanisms of Drug Delivery** - Dendrimer drug delivery involves use of dendrimers, highly branched macromolecules, as carriers for delivering therapeutic agents such as drugs, as they offer a high drug-loading capacity. - Methods aim to enhance drug solubility, stability, targeted delivery, and controlled release. ### **Common Methods of Dendrimer Drug Delivery:** 1. Encapsulation of drugs 2. Covalent Dendrimer – drug conjugates ### **Encapsulation of Drugs (Non-Covalent)** 1. Dendrimers with branched 3D structures & internal cavities allow drugs to be physically encapsulated through electrostatic / hydrophobic interactions. 2. Loaded drugs are stabilized in dendrimer or dendrimer network at their cavities, not covalently bound. 3. This encapsulation ensures drug stability under normal conditions. 4. Drug released by external factors such as UV or visible light. 5. Non-covalent nature allows controlled release without chemical modification of drugs (Not conjugates with drug active site) ### **Drug Conjugates (Covalent Dendrimer)** 1. Drugs are chemically conjugated to dendrimers through biodegradable linker or spacer, forming dendrimer-drug conjugates or prodrugs. 2. This enhances drug stability, solubility, & allows for controlled release. ### **Role of Dendrimer at Drug Delivery Methods:** 1. Protection of Drug From enzymatic degradation 2. Solubility Enhancement: Solubility of poorly soluble drugs 3. Controlled Release: Allowing gradual release of the encapsulated drug over time ## **Nano Capsules (Polymers – organic - Nanomaterials)** - **What are Nano Capsules?** - They're colloidal nano-bubbles in which core (oily or aqueous) & surrounded by a polymeric membrane with specific properties. ### **Polymeric Membrane** 1. Aqueous core contain hydrophilic core surrounded by an amphiphilic membrane. 2. For drug loading, core material is selected based on desirable drug-core interactions - ionic, H-bonding, etc. 3. For imaging, gold or iron oxide is commonly used 4. The polymeric membrane selection depends on factors like biocompatibility, stability and permeability. 5. Drugs diffuse into the aqueous core based on a concentration gradient 6. Encapsulation protects drugs from degradation & allows controlled release 7. Scale-up requires development of safer, validated processes without harsh organic solvents. ### **Disadvantage** 1. Extensive use of poly vinyl alcohol as a detergent issues with toxicity. 2. Limited targeting abilities. 3. Cytotoxicity. 4. Discontinuation of therapy is not possible 5. Alveolar inflammation. 6. Pulmonary inflammation & pulmonary carcinogenicity. 7. Disturbance of autonomic imbalance by Nano particles having direct effect on heart and vascular function. ## **Preparation of Nano capsules:** | Method | Materials | Pathway | Drug Example | |---|---|---|---| | **Nano precipitation** | 1. Active Sub. 2. Polymer 3. Oil 4. W/O surfactant 5. Solvent 6. Stabilizer 7. Non solvent | Organic Slow Injection (Dropwise & moderate stirring) Aqueous Phase | Indomethacin Polymer: PCL MW10 Oil Core: Mineral Oil Solvent: Aceton use: Anti-inflammatory | | **Emulsion Diffusion** | 1. Active Sub. 2. Polymer 3. Oil 4. Inner phase Solvent 5. Stabilizer 6. External phase Solvent | Organic Phase + Aqueous Phase High shear mixer) Emulsification (Aqueous phase) Dilution Phase Diffusion (Moderate stirring) | Indomethacin 1. Inner phase Polymer: PCL MW10 Core: Caprlyic TG Solvent1: Ethyl Acet. 2. External phase Stabilizer agent: PVA Solvent 2: Water 3. Dilution Phase: Water 4. Use: Anti-inflammatory | | **Double Emulsification** | 1. Inner aqueous phase a) Active sub. b) Water 2. Organic phase a) Polymer b) W/O surfactant c) Solvent 3. External aqueous phase a) Stabilizer agent b) Water | Organic Phase + Aqueous phase 1 Emulsification W/O (Sonication) Aqueous phase 2 Emulsification (Sonication or high shear mixer) Oil Phase + Aqueous phase 1 Emulsification W/O (Sonication) Solvent Removal Formulation of Polymer Coat | Insulin 1. W 1 Phase: Active Ing, H2O 2. Organic Phase: PLA MW, Sorbitan 3. W 2 Phase Polysorbate, Glycerin, Water 4. Use: Anti-Diabetic | | **Polymer Coating** | | Organic Phase + Aqueous phase 1 Emulsification W/O (Sonication) Solvent Removal Formulation of Polymer Coat | Ca Regulator 1. Organic Phase Active Ing, Acetone 2. Aqueous Phase: Water 3. Coating Chitosan Oligomers 4. Use: Calcium Regulator | ## **Nanospheres (Polymers – organic – Nanomaterials)** - **What are Nanospheres?** - Nanospheres structural polymeric matrix composite of spherical shape, size between 10 & 200nm in diameter. - A bioactive is entrapped, dissolved, encapsulated, or attached to polymeric matrix composite. - The character of nanospheres can be crystalline or amorphous. - Designed to protect bioactives from chemical and enzymatic degradation (Such as Nanocarriers). ### **Methods for Preparation Nanospheres:** 1. Emulsification polymerization 2. solvent evaporation 3. solvent displacement technique ### **Types of Nanospheres:** 1. Nonbiodegradable nanospheres 2. Biodegradable nanospheres - Albumin Nanospheres - Gelatin Nanospheres - Polypropylene Dextran Nanospheres - Modified-Starch Nanospheres. ## **Liposomes (Lipids – organic – Nanomaterials)** - **What are Liposomes?** - Liposomes are concentric bilayered vesicles with aqueous core is entirely enclosed by a membranous lipid bilayer mainly composed of natural or synthetic phospholipids. - Size of liposome ranges from 20 nm up to several micrometers. - Lipid molecules usually phospholipids- amphipathic moieties with a hydrophilic head group and two hydrophobic tails. - On addition of excess water, such lipid moieties spontaneously originate to give most thermodynamically stable conformation. ## **Basic Liposome Structure** 1. Hydrophobic Region 2. Drug In Aqueous Medium 3. Hydrophilic Region 4. Phospholipid Bilayer ## **Methods of Liposome Preparation** ### **Passive Loading Techniques** - **Solvent Dispersion Methods** - Ethanol injection - Ether Injection - Double emulsion Vesicles - Stable plurilamellar - Vesicles Revere phase evaporation vesicles ### **Active Loading Techniques** - **Detergent Removal Methods** - Detergent (Cholate Alkyl Glycoside, Triton X-100) removal from mixed micelles by Dialysis - Column Chromatography - Dilution - Reconstituted sendai virus enveloped vesicles ## **Types of liposomes** 1. Unilamellar liposomes 2. Multilamellar liposomes ## **On the Basis of Structural Parameters** | **Type** | **Description** | |---|---| | MLV | Multilamellar vesicles (>0.5 µm) | | OLV | Oligolamellar vesicles (0.1-1 um) | | UV | Unilamellar vesicles (all size range) | | SUV | Small unilamellar vesicles (20-100 nm) | | MOV | Medium sized unilamellar vesicles | | LUV | Large unilamellar vesicles (> 100 μm) | | GUV | Giant unilamellar vesicles (>1 µm) | | MVV | Multi vesicular vesicles (>1 µm) | ## **On the Basis of Liposome Preparation** | **Type** | **Description** | |---|---| | MLV | Vesicles prepared by reverse phase evaporation method | | OLV | Oligolamellar vesicles by REV | | UV | Multi lamellar vesicle by REV | | SUV | Stable plurilamellar vesicle | | MOV | Frozen & thawed MLV | | LUV | Vesicles prepared by extrusion techniques | | GUV | Dried reconstituted vesicles | | MVV | | ## **Phosphatidylcholine** - Most common phospholipids used is phosphatidylcholine (PC). - Phosphatidylcholine is an amphipathic molecule consist of: - Hydrophilic polar head group, phosphocholine. - Glycerol bridge. - Pair of hydrophobic acyl hydrocarbon chains. ## **Advantages** 1. Provides selective passive targeting to tumor tissues. 2. Increased efficacy & therapeutic index. 3. Increased stability of encapsulated drug. 4. Reduction in toxicity of the encapsulated agent. 5. Site avoidance effect (avoids non-target tissues). 6. Improved pharmacokinetic effects (reduced elimination increased circulation life times). 7. Flexibility to couple with site specific ligands to achieve active targeting. ## **Disadvantages** 1. Physical/chemical stability 2. Very high production cost 3. Drug leakage/ entrapment/ drug fusion 4. Sterilization 5. Short biological activity / t 1/2 6. Oxidation of bilayer phospholipids and low solubility 7. Rate of release and altered bio distribution 8. Low therapeutic index and dose effectiveness 9. Overcoming resistance 10. Extensive clinical and laboratory research to a certain long circulating liposomes 11. Repeated iv administration problems ## **Micelle (Lipids – organic – Nanomaterials)** - **What is Micelle?** - Micelle is an aggregate of monomer surfactant molecules dispersed in a liquid colloid. ### **Types of Micelle** 1. **Oil-in-water micelle** - Hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic tail regions in the micelle centre. - Because of arrangement monomers micelle is capable to hold lipidic nature drug at centre 2. **Water-in-oil micelle** - Inverse micelles have the head groups at the centre with the tails extending out (water-in-oil micelle). - In Reversed micelle at middle able to hold relatively large amounts of water in their interior. In that way, a "pocket" is formed which is particularly suited for the dissolution and transportation of polar solutes through a non-polar solvent. ### **Micelle formation** - Typical micelle is Spherical structure contain 50-100 monomers. - Number of monomers to form micelle called: aggregation number. ## **Factors Affecting Process of Micelles Formation** - Molecular wt. of monomer - Aggregation no. - Proportion of hydrophobic and hydrophilic chain length - Preparation process ## **Critical Micelle Concentration (CMC)** - Lowest conc. at which micelles first appear called critical conc. for micelle formation - Critical Micelle Concentration is the point at which surfactant molecules aggregate together in the liquid to form groups known as micelles. ## **Applications** 1. **Increase Solubility** - Micelle can be used to increase the solubility of material that are normally insoluble or poorly soluble in dispersed medium phenomenon called as solubilization. 2. **Drug Protection** - Protection of drug molecules from degradation via hydrolysis or other physicochemical reactions, this increases their shelf life, or prolongs their stability during use. 3. **Targeted Drug Delivery** - Micelles may have an increasingly important role as carriers of drug molecules to target sites, for example, delivering doxorubicin to a tumor.

Fundamental Nanoscience (Lectures 1-3) PDF

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