P8: Formulation of Liposomes & Gels

Question 1

what are gels

Answer 1

viscoelastic solid-like materials comprised of an elastic cross-linked network and a solvent which is the major component

Question 2

why does gel have a solid appearance

Answer 2

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

Question 3

how is a solid matrix formed

Answer 3

cross-linking of the polymetric strands of macro molecu;es by physical or chemical forces

Question 4

what are the characteristics of gel

Answer 4

large increase in viscocity above gel point
appearance of rubber-like elasticity
gel retains shape under low stress but deforms at higher stress

Question 5

what are some examples of naturally occurring gelators

Answer 5

gelatin, collagen, agar, starch, gellan gum

Question 6

what are the two classifications of gels derived from synthetic compounds

Answer 6

macromolecular (polymer)

supramolecular

Question 7

what are the components of a gel

Answer 7

water (hydrogels)
organic liquid (organogels)

Question 8

what are some features of hydrogels

Answer 8

retain a significant amount of water

remains water-insoluble, used in topical drug delivery, soft contact lenses, implant coating

Question 9

what determines the diffusion rate of a drug in a hydrogel

Answer 9

the physical structure of the polymer network and its chemical nature
if gel is highly hydrated, diffusion occurs through the pores
if gel hydration is low, drug dissolves in the polymer and is transported between the chains

Question 10

how does cross linking affect hydrogels

Answer 10

increases hydrophobicity of a gel

decreases the diffusion rate of the drug

Question 11

what factors can change swelling characteristics of hydrogels and drug release

Answer 11

heat, pH, application of electrical current

results in responsive drug delivery - ‘on off’ switching mechanism

Question 12

what causes a gel to become thermally irriversible

Answer 12

when gels are formed by strong chemical bonds

Question 13

what causes a gel to be reversible

Answer 13

gels formed by weak non-covalent interactions (physical entanglements)

Question 14

what are type 1 gels

Answer 14

irriversible systems
3D network formed by covalent bonds between macromolecules
formed by polymerisation of monomers of water soluble polymers in presence of cross-linking

Question 15

what are type 2 gels

Answer 15

heat-reversible
held together by intermolecular bonds
gel on cooling below gel point

Question 16

how are type 2 PVA solutions used

Answer 16

they have suitable gelling properties for topical skin applications
gel dries rapidly leaving plastic film with drug in intimate contact with skin

Question 17

how are cross-linked polymetric systems formed

Answer 17

water-soluble polymer chains are covalently cross-linked into a 3D structure
gel forms when dry material interacts with water
polymer swells but cannot dissolve due to cross-linking

Question 18

what are some applications of cross-linking polymetric systems

Answer 18

applications include fabrication of expanding implants; e.g. polyglycol methacrylate cross linked with ethylene glycol dimethycrylate gels loaded with antibiotics to treat middle ear infections

Question 19

what does SAFIN stand for

Answer 19

self-assembled fibrillar networks

Question 20

how are SAFINs formed

Answer 20

through self-aggregation of the small gelator molecules using non-covalent interactions

Question 21

what are some examples of non-covalent interactions

Answer 21

H-bonding, pi-stacking, donor-acceptor interactions, metal coordination, solvophobic forces (hydrophobic forces for gels in water), Van der Waals

Question 22

how are gels of low molecular mass compound formed

Answer 22

by heating the gelator in an appropriate solvent and cooling the resulting isotropic supersaturated solution to room temperature
when the hot solution is cooled, the molecules start to condense and three situations are possible

Question 23

what are the three possible outcomes of low molecular compound gels being heated and cooled

Answer 23

1. highly ordered aggregation giving rise to crystals
2. random aggregation resulting in an amorphous precipitate
3. aggregation process intermediate between these two, yielding a gel

Question 24

what are some applications for supramolecular gels

Answer 24

media for tissue engineering (natural and synthetic polymers in hydrogels have similarity to macromolecular component of the body)
many supramolecular hydrogels derived from natural molecules (biocompatibility so used for similar applications)

Question 25

how are micelles formed

Answer 25

at low amphiphile concentration, the molecules will be dispersed randomly without ordering at slightly higher concentration, amphiphilic molecules will spontaneously assemble into micelles or vesicles, this hides the hydrophobic tail of the amphiphile inside the micelle core

Question 26

what happens at high micelle concentration

Answer 26

the assemblies become ordered, a typical phase is a hexagonal columnar columnar phase. where amphiphiles form long cylinders that arrange themselves in a hexagonal lattice (called middle soap phase) even higher concentration, lamellar phase (neat soap phase) may form where extended sheets of amphiphiles are separated by thin layers of water

Question 27

what are liposomes

Answer 27

vesicular structures based on one or more lipid bilayers encapsulating an aqueous core; considered as liquid capsules

Question 28

what lipid molecules are in liposomes

Answer 28

usually phospholipids with hydrophilic head groups and two hydrophobic chains

Question 29

how do liposomes reduce exposure at the edges

Answer 29

the bilayers self-close into one or more concentric compartments around a central discrete aqueous phase can be multilamellar or unilamellar

Question 30

what can liposomes carry

Answer 30

strongly lipophilic drugs fully buried in lipid bilayer strongly hydrophilic drugs sequestered in the aqueous interior of the liposome drugs with intermediate logP partition between the lipid and aqueous phases

Question 31

what is phosphatidylcholine

Answer 31

natural phospholipid as the major lipid component used in the preparation of pharmacuetical liposomes

Question 32

what determines the rigidity and permeability of the bilayer

Answer 32

depends on the type and quality of lipids used alkyl chain length and degree of unsaturation presence of cholesterol can also increase rigidity

Question 33

what determines stability of liposomes

Answer 33

lipid composition, storage condition, stabalisers

Question 34

what are the features of liposomes

Answer 34

biologically inert, weakly immunogenic, low intrinsic toxicity, composed of natural phosphilipids

Question 35

what are conventional liposomes

Answer 35

neural or negatively charged, generally used for passive targeting to the cells of mononuclear phagocyte systems

Question 36

what are sterically stabalised liposomes

Answer 36

carry hydrophilic coatings, used to obtain prolonged circulation times

Question 37

what are immunoliposomes

Answer 37

either conventional or sterically stabalised, used for active-targeting purposes

Question 38

what are cationic liposomes

Answer 38

positively charged and used for the delivery of genetic material

Question 39

what are conventional liposomes for

Answer 39

protect encapsulated molecules from degredation can passively target tissues or organs that have discontinuous endothelium rapidly taken up by phagocytic cells of mononuclear phagocyte system localising in liver and spleen in IV administration

Question 40

how do long circulating liposomes work

Answer 40

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

Question 41

how do immunoliposomes work

Answer 41

they have specific antibodies or antibody fragments on their surface to enhance target site binding

Question 42

how do cationic liposomes work

Answer 42

cationic lipid components of the liposomes interact with and neutralise, negatively charged DNA, thereby condensing the DNA into a more compact structure the complex may not be a simple aggregate, but an intricate structure where condensed DNA is surrounded by a lipid bilayer

Question 43

how toxic are liposomes

Answer 43

most are well-tolerated cationic liposomes may activate complements and induce adverse effects via IV route PEGylated liposomes may induce a transient reaction upon injection in a subset of patients