P8

Define gels?

Viscoelastic solid like materials comprised of elastic cross linked network and a solvent, relatively unaffected by thermal motion

Why do gels have a solid like appearance?

The result of liquid entrapment and adhesion of the liquid in the large surface area of a solid 3D matrix

Characteristics of gels?

Large increase in viscosity above gel point, appearance of rubber like elasticity, retains shape under low stress but not high stress

What are most naturally occurring gels?

Macromolecules and form gels via physical crosslinking, hydrogen bonds

What is a xero gel?

A gel when all the liquid has been removed

Are hydrogels water soluble?

No

Name some of the uses of hydrogels?

Topical drug delivery, wound healing, soft contact lenses

Explain the mechanism of diffusion in a hydrogel that is highly hydrated?

Diffusion occurs through pores

Explain the mechanism of diffusion in a hydrogel that the gel hydration is low?

Drug dissolves in polymer and is transported between chains

What does crosslinking of the polymer lead to?

Increased hydrophobicity of the gel, decreases the diffusion rate of the drug

How can the swelling characteristics of the drug be changed?

Via heat, pH or application of electrical current

What are the characteristics of chemically bonded gels?

They cannot be dissolved and are thermally irreversible

Define a type I gel?

3-D network of formed by covalent bonds between macro molecules, irreversible system

Define a type II gel?

Held together by intermolecular bonds

What are type II gels suitable for?

Topical applications to the skin, gels dry rapidly leaving plastic film with drug in intimate contact with the skin

What happens when a water soluble covalently x-linked polymers come in contact with water?

Gel forms but cannot dissolve due to x links

What is a supramolecular gel?

Made from low molecular mass compounds

What can water soluble covalently x-linked polymers be used for?

Fabrication of expanding implants

How are supramolecular gels formed?

Self aggregation of the small gelator molecules to form self-assembled fibrilliar networks

What no covalent interactions form SAFINs?

H bonds, pi stacking, donor acceptor interactions, metal co-ordinations solvophobic forces, vdws

Explain how supramolecular gels are prepared?

By heating the gelator in appropriate solvent, cooling resulting isotropic supersaturated solution at room temperature

What are the 3 situations that can arise when the supramolecular gel is formed?

Highly ordered aggregation forming crystals, random aggregation forming in an amorphous precipitate, an intermediate of the two forming a gel

What are the applications of supramolecular gels>

Cosmetic, biomedical hydrogels and tissue engineering, controlled release formulations, wound dressings

Define the middle soap phase?

At high concentrations amphiphiles form long cylinders and arrange themselves roughly into a hexagonal lattice

Define the neat soap phase?

At the highest concentration, extended sheets of amphiphiles are separated by thin layers of water

Define Liposome?

Vesicular structures based on one or more lipid bilayers encapsulating an aqueous core, liquid crystals

Why do liposomes form?

In water the bilayer structures enclose on themselves in to one or more compartments

Explain a multilamellar liposome?

A multitude of concentrically orientated bilayers that surrounds an aqueous core

How can liposomes carry lipophilic drugs?

Fully buried in the lipid bilayer

How do liposomes carry hydrophilic drugs?

In the aqueous interior of the liposome

How do liposomes carry intermediate log P drugs?

Between the lipid and aqueous phases, membrane associated drugs

Name to commonly used lipids in liposome bilayers?

Phosophatidylethanolamine, Phosphatidylethanolamine

What 2 factors play a major role in the rigidity and permeability of the bilayer?

Alkyl-chain length and degree of unsaturation and the presence of cholesterol

What can changing the rigidity and permeability of a liposome do?

Can change how long the drug stays entrapped for, there for changing the release profile of the drug

Describe what liposome stability depends on?

Lipid composition, storage, stabilisers, cholesterol, some can be lyophilised

What do dry phospholipids do in water?

They rapidly swell above a certain value

Why are liposomes attractive drug carriers?

Bio-compatible in large amounts , biodegradable, inert, weakly immunogenic, low intrinsic toxicity, biodistribution, can target specific receptors,

Name the 4 types of liposomes

Conventional, sterically stable, immunoliposomes, cationic

Define conventional liposomes?

Typically composed of only phospholipids neutral or negatively charged and cholesterol

Describe the application of conventional liposomes?

Protect encapsulated molecules from degradation, can target tissues with discontinuous endothelium, rapidly taken up in to the MPS

Example of the application of conventional liposomes?

Parental delivery of antifungal Amphotericin B, encapsulation of anti cancer drugs, antigen delivery

Define sterically stable liposomes?

Liposomes that have covalently attached hydrophilic PEG to the liposome bilayers making them long circulating liposome bilayers

What is the function on of the PEG group on long circulating liposomes?

The highly hydrated PEG group creates a steric barrier against interactions with molecular and cellular components in the biological environment

Define Immunoliposomes?

Have specific antibodies or fragments on their surface to enhance target binding

What are the applications of Immunoliposomes?

Delivery of anticancer agents

What is the preparation of of long circulating liposomes and immunoliposomes?

Anti body can be coupled directly to the surface but PEG chains may hinder binding, can also be coupled to the end of the PEG chains

Applications of cationic liposome?

Delivery of DNA

Explain the MOA behind the binding of cationic liposomes and DNA?

Cationic parts of liposome interact with negatively charged DNA condensing the DNA into a more compact structure

What are some of the toxicity problems with liposomes?

cationic liposomes may active complements via IV, PEG liposomes may induce a transient reaction in some patients