Colloidal Dispersions Specific Aims PDF

[Assignment 2]  [Colloidal dispersions -- specific aims  ]      1\. Be able to define dispersion systems and colloidal systems. What is the typical size range of colloidal particles? Do some suspensions and emulsions contain a range of particle size such that the smaller particles lie within the...

[Assignment 2]  [Colloidal dispersions -- specific aims  ]      1\. Be able to define dispersion systems and colloidal systems. What is the typical size range of colloidal particles? Do some suspensions and emulsions contain a range of particle size such that the smaller particles lie within the colloidal range, whereas the larger ones are classified as coarse particles?  Answer: Dispersion systems consist of one component: the disperse phase, dispersed as particles/droplets throughout another component: the continuous phase. Colloidal systems consist of dispersed particles, whose size ranges between 1-1000nm, suspended in a dispersion medium. Yes, some suspensions and emulsions contain a range of particle size such that the smaller particles lie within the colloidal range, whereas the larger ones are classified as coarse particles.   2\. Be able to explain the effects of shape and size of colloidal particles on their properties. Is the surface area of colloidal particles large compared with the surface area of an equal volume of larger particles?  Answer: The surface area of colloidal particles is significantly larger compared to the surface area of an equal volume of larger particles. This is due to the much smaller size of the colloidal particles, which leads to a higher surface to volume ratio. The effects of shape and size of colloidal particles on their properties are surface area and reactivity, optical properties, stability, sedimentation, diffusion, and electrical properties. The comparison of the surface area is increased of colloidal particles that play a key role in their unique properties and behaviors compared to bulk materials.    3\. Be able to define and describe major characteristics of lyophilic, lyophobic, and association colloids. Which type(s) of colloids interact(s) to an appreciable extent, and has/have affinity toward the dispersion medium? Which type(s) of colloids is/are formed spontaneously? Which type(s) of colloids is/are covered with a solvent sheath?  Answer: Lyophilic means only when applied to the material dispersed in a specific dispersion. A material may form a lyophilic colloidal system in one liquid but that does not mean it will in a different liquid. The dispersed particles are covered with a solvent sheath. Lyophilic colloids contain colloidal particles that interact to an appreciable extent with the dispersion medium. Lyophilic colloids have an affinity toward the dispersion medium.   Unlike lyophilic colloids, lyophobic colloids have little affinity toward the dispersion medium. Lyophobic colloids do not have a solvent sheath.  Amphiphiles tend to associate into larger aggregates when dissolved in water or oil and are designated as association colloids because their aggregates are large enough to qualify as colloidal particles. The colloids that form spontaneously are association and lyophilic colloids.  4\. Be able to describe for lyophilic colloids whether a material that forms such a system in one liquid (e.g., water) will necessarily do so in another liquid (e.g., benzene). Are lyophilic colloids always formed in aqueous dispersion media? In which dispersion medium are hydrophilic and hydrophobic colloids formed? Can insoluble but extensively solvated particles dispersed in a liquid medium that has a high affinity or attraction to them form hydrophilic colloids? Do such particles dissolve or break down into individual molecules or ions?  Answer: Lyophilic colloids formed in one system may not be formed in another system due to properties of the material and system; a material that forms a lyophilic colloid in one liquid like water, it will not form a lyophilic colloid in another liquid. The ability of a substance to form a colloid is highly dependent on the interaction between the substance and the solvent. No, lyophilic colloids are not *always* formed in aqueous dispersion media.  Aqueous solutions are commonly used because water is a polar solvent. Hydrophilic colloids are typically formed in polar solvents, like water. Hydrophobic colloids, on the other hand, tend to form in non-polar solvents, such as benzene or organic solvents. Yes, if particles are insoluble but are in a medium that has a strong affinity for them, the particles can form hydrophilic colloids. This doesn\'t necessarily mean the particles dissolve into individual ions or molecules, but rather that they are dispersed in the solvent with solvent molecules surrounding them. No, lyophilic colloids typically do not dissolve or break down into individual molecules or ions. Instead, they form a colloidal dispersion where the particles remain intact but are dispersed throughout the solvent. The formation of lyophilic colloids depends on the interaction between the particles and the solvent.    5\. Be able to describe hydrophilic colloids (hydrocolloids), including the main types of materials that can form them. For water soluble polymers acting as hydrophilic colloids is each particle made from a single molecule?   Answer: Hydrophilic colloids are insoluble but extensively solvated particles dispersed in a liquid medium that have high attraction to water. Hydrophilic colloids will swell in water and spontaneously break into particles that have colloidal dimensions. Materials that form hydrocolloids include natural polymers and cellulose derivatives. Natural polymers include substances such as starch and xanthan gum. Cellulose derivatives are mostly found in plants. Yes, in a hydrophilic colloid each particle is made from a single molecule.    6\. Be able to describe for lyophobic colloids whether their preparation requires various physical and chemical considerations for the reduction of particle size to the colloid range. Are particles of hydrophobic colloids hydrated by their dispersion medium? Which type of colloids do intravenous fat emulsions form?  Answer: Lyophobic colloids, like metal colloids, require specific physical or chemical methods to reduce particle size to the colloidal range, such as grinding, milling, or chemical reduction. Hydrophobic colloids are not naturally hydrated by their dispersion medium, like water and need stabilizers, such as surfactants, to stay dispersed. Intravenous fat emulsions form lyophilic colloids, stabilized by emulsifiers to allow fat to mix with the aqueous medium.  7\. Be able to describe the (3) major types of association colloids, and on which type of materials are they based on?   Answer: The 3 major types of association colloids are micelles, microemulsions, and liposomes. Micelles are based on amphiphilic molecules like surfactants, and they self-assemble in an aqueous or organic solvent. Microemulsions are based on oil and water phases with carefully selected surfactants. Liposomes are based on phospholipid and polymer-based bilayer vesicles.  8\. Be able to describe micelles and their main characteristics, including size and how many monomers does each micelle contain. Do micelles and amphiphiles that exist separately in a low concentration at a liquid medium have colloidal or subcolloidal dimensions? What would be the typical environment in the core of micelles formed in an aqueous dispersion medium? Are micelles static aggregates? In an aqueous dispersion medium, where will amphiphiles go first, to the air-water interface or to the bulk phase?  Answer: When present in a liquid medium at low concentrations, amphiphiles exist separately and are of such a size as to be sub-colloidal. As the concentration is increased aggregation is increased, and aggregation occurs over a narrow concentration range. These aggregates are called "micelles" and may contain between 50-100 monomers.   Micelles and amphiphiles that exist separately in a low concentration at a liquid medium have a sub-colloidial dimension.   The typical environment in the core of micelles is a hydrophobic environment, as the hydrocarbon chains face inward, shielding themselves from the aqueous environment, while the polar portions surround the hydrocarbon core to maintain solubility in water.  Micelles are not static aggregates.  In an aqueous dispersion medium, amphiphiles will initially migrate to the air-water interface. Eventually, a point is reached where the interface and the bulk phase become saturated with monomers; this is known as the critical micelle concentration. Upon further addition of amphiphiles, they will begin to form aggregates, such as micelles, in the bulk phase.     9\. Be able to describe the Critical Micelle Concentration (CMC). In concentrations above the CMC, where will additional amphiphile added to the system go? Is the surface tension substantially reduced above or below the CMC? Is the solubility of water-insoluble solubilization increasing above or below the CMC?  Answer: Critical Micelle Concentration is the concentration of monomer at which micelles form. Amphiphiles above the CMC will go to the bulk phase. The surface tension substantially reduces below the CMC. The solubility of water-insoluble solubilization increases above CMC.   10\. Be able to describe the main pharmaceutical applications of colloidal dispersion systems. Do some of the biotechnology drugs form colloidal dispersions?   Answer: The main pharmaceutical applications of colloidal dispersion systems:  11\. Be able to define solubilization. To which systems does this term usually refer to? In which part of the micelle will nonpolar, slightly polar, and an amphipathic solubilizate reside? Is the site of solubilization within the micelle closely related to the chemical nature of the solubilizate? What may be the result of using excessive amounts of surfactants in a micelle system? If the system has an insufficient concentration of surfactants so that the number of micelles formed is small, how may this affect the solubilizate?  Answer: Solubilization is when water-insoluble or partly soluble substances are brought into aqueous solution by incorporation into micelles.  Nonpolar solubilizate will reside in the center of the micelle, slightly polar solubilizate will reside partially inside the micelle or fully in the micelle, and amphiphilic solubilizate have hydrophobic and hydrophilic portions so it will reside partially on the surface of the micelle and partially on the inside. Yes, the site of solubilization within the micelle is closely related to the chemical nature of the solubilizate. If excessive amounts of surfactants are in the micelle system, it can cause toxicity. If the system has an insufficient concentration of surfactants this will cause precipitation of the solubilizate.       12\. Be able to describe for Adult Infuvite Multiple Vitamins for Infusion which vitamins are most likely to be solubilized, and which inactive ingredient is responsible for solubilization?  Answer: Vitamin A palmitate is most likely to be solubilized in Adult Infuvite Multiple Vitamins for infusions. Vitamin k1, alpha-tocopherol acetate, and cholecalciferol are the inactive ingredients that are responsible for solubilization.    13\. Be able to describe major characteristics, advantages and disadvantages of microemulsions. Typically how many surfactants are required in a microemulsion formulation to lower the interfacial tension? Is the amount of surfactants in microemulsions small or large? Are microemulsions formed spontaneously? Are they more appropriate as carriers of hydrophilic or lipophilic drugs? Is their preparation more simple or difficult in comparison to the preparation of coarse emulsions?  Answer: Advantages of microemulsions include physical stability (they do not seperate overtime and do not require energy to remain stable), they help to solubilize lipohillic drugs (drugs that are lipophillic typically are not soluble but microemulsions allow them to be more soluble, drug release is increased by smaller droplet size (increases due to surface area). Typically, two surfactants are used to lower interfacial tension between oil and water phases. The amount of surfactant in microemulsions is relatively large; to achieve stability. Microemulsions do usually form spontaneously given proper surfactants, composition, and low interfacial tension. Microemulsions are typically favored for lipohillic drugs because of their compatibility with the oil phase. The preparation is more difficult than coarse emulsions because of the precise formulation of surfactants, concentrations, and oil/water ratio        14\. Be able to define liposomes and to describe different types of liposomes and what are the major differences between them, including advantages and disadvantages. Are liposomes vesicles consisting an aqueous core surrounded by concentrically arranged monolayer or bilayer membranes? Which type of materials are the main components of liposomes? What is the possible contribution of cholesterol to the liposome structure? Can liposomes accommodate water-soluble drugs, lipid-soluble drugs, or both? In which regions of the liposomes will drugs reside?  Answer: Liposomes are spherical vesicles consisting of an aqueous core surrounded by one or more bilayer membranes that are commonly composed of phospholipids. The different types of liposomes consist of MLV which is multilamellar vesicle, LUV which is large unilamellar vesicle, and SUV which is small unilamellar vesicles. MLV are large and have multiple layers, advantages are that they have a higher stability and some disadvantages are lower encapsulation efficiency, LUV are large single layer, advantages are that these are easy to prepare and have efficiency for hydrophilic drugs and disadvantages are limited stability so compromise between size and entrapment efficiency, with SUV are small with one layer are efficient with tissue penetration and prolonged circulation but are potentially unstable do to small size. Phospholipids are the main component with phosphatidylcholine as the major component. Cholesterol can be inserted into the bilayers to contribute rigidity to the structureand reduce permeability. Liposomes can accommodate both water and lipid soluble drugs. The water-soluble drugs will reside in aqueous areas, and lipid soluble drugs with be within the lipid bilayer.   15\. Be able to describe the factors that determine whether a molecule dispersed in an aqueous system will form micelles or liposomes. Which factor is the most important in determining whether micelles or liposomes will be formed?  Answer: The primary factor determining whether a molecule disperses in an aqueous system will form micelles or liposomes is its molecular shape and amphiphilicity. This will dictate the molecule's geometry and packing behavior. Molecules with the conical shape (single tail) tend to form micelles, while molecules with a cylindrical shape (two tails) favor the formation of bilayers that can curve into liposomes. The key factor in determining this structure is the critical packing parameter (CPP), which relates the hydrophobic tail volume, hydrophilic head area, and tail length. Other factors like concentration and temperature can also play a role but are less critical.   16\. Be able to describe drug release from liposomes. What is a major factor needed for drug release?  Answer: Interaction with cells is usually needed to release the drug either through passive diffusion and absorption at the cell membrane, through the lipids of the liposome and membrane, and endocytosis and phagocytic cells emptying the entire contents of the drug making it available to the cell. A major factor needed for drug release is enhanced permeability and retention effects. The drug needs to be released at the right time. As such, many of these drugs are designed for intravenous injections.   17\. Be able to describe the fate of liposomes after intravenous injection. What is the typical half-life of liposomes? What is the effect of uptake by the Mononuclear Phagocyte System (MPS) on the fate of liposomes? Is the uptake by the MPS always undesirable?   Answer: After intravenous injection, liposomes circulate in the bloodstream, with their fate determined by factors like size, charge, lipid composition, and surface modifications. Unmodified liposomes are rapidly cleared by the Mononuclear Phagocyte System, specifically by macrophages in the liver and spleen. This causes a shorter half-life for the liposomes, whereas their half-life typically is minutes to hours. While MPS uptake reduces drug availability for non-MPS targets, it can be beneficial in treating MPS-related diseases. The uptake of liposomes by the Mononuclear Phagocyte System (MPS) is not always undesirable. While it can limit the availability of liposomes for non-MPS targets by reducing circulation time, MPS uptake can be beneficial in specific therapeutic scenarios  18\. Be able to describe stealth liposomes and their effect on MPS uptake of liposomes. What is the main characteristic of stealth liposomes? Which specific polymers are most commonly used for grafting or coating liposome surfaces to design stealth liposomes, and are these polymers water soluble or water insoluble? What would be an example of the half-life of a product that evades the MPS?  Answer: Stealth liposomes create highly hydrated layers on the surface of the liposomes by coating/ grafting with water-soluble polymers. This allows them to evade MPS by increasing circulation in the blood stream thus enhancing drug delivery efficiency. Doxil is an example of a stealth liposome whose half-life is extended up to 55 hours via pegylation.     19\. Be able to describe advantages and disadvantages, including the main disadvantage, of liposomes. Are drugs encapsulated in liposomes more or less susceptible to degradation?    Answer: Advantages of liposomes are that they are nontoxic, biodegradable, they can deliver water and oil soluble drugs, and they have the ability to target drugs. Disadvantages of liposomes include low encapsulation efficiency of some drugs, challenging scale up and sterilization, may require freeze drying (lyophilization) for stabilization, and the [rapid removal from the blood following intravenous administration by cells of the MPS which is the primary disadvantage {underlined}]. Encapsulated drugs are less susceptible to degradation.   20\. Be able to describe the mechanism that underpins the targeting of liposomes to tumor cells.  21\. Be able to define nanotechnology and nanoparticles. What are the (3) main types of nanoparticles?   22\. Be able to describe Abraxane. Can binding albumin to a drug with low solubility such as paclitaxel promote targeting to tumor cells, and if so then what are the mechanisms underlying this phenomenon?