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Respiratory Diseases & Dermatology > P8: Formulation of Liposomes & Gels > Flashcards

P8: Formulation of Liposomes & Gels Flashcards

1
Q

what are gels

A

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

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2
Q

why does gel have a solid appearance

A

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

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3
Q

how is a solid matrix formed

A

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

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4
Q

what are the characteristics of gel

A

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

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5
Q

what are some examples of naturally occurring gelators

A

gelatin, collagen, agar, starch, gellan gum

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6
Q

what are the two classifications of gels derived from synthetic compounds

A

macromolecular (polymer)

supramolecular

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7
Q

what are the components of a gel

A 
water (hydrogels)
organic liquid (organogels)
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8
Q

what are some features of hydrogels

A

retain a significant amount of water

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

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9
Q

what determines the diffusion rate of a drug in a hydrogel

A

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

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10
Q

how does cross linking affect hydrogels

A

increases hydrophobicity of a gel

decreases the diffusion rate of the drug

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11
Q

what factors can change swelling characteristics of hydrogels and drug release

A

heat, pH, application of electrical current

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

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12
Q

what causes a gel to become thermally irriversible

A

when gels are formed by strong chemical bonds

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13
Q

what causes a gel to be reversible

A

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

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14
Q

what are type 1 gels

A

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

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15
Q

what are type 2 gels

A

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

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16
Q

how are type 2 PVA solutions used

A

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

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17
Q

how are cross-linked polymetric systems formed

A

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

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18
Q

what are some applications of cross-linking polymetric systems

A

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

19
Q

what does SAFIN stand for

A

self-assembled fibrillar networks

20
Q

how are SAFINs formed

A

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

21
Q

what are some examples of non-covalent interactions

A

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

22
Q

how are gels of low molecular mass compound formed

A

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

23
Q

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

A
  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
24
Q

what are some applications for supramolecular gels

A

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)

25
Q

how are micelles formed

A

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

26
Q

what happens at high micelle concentration

A

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

27
Q

what are liposomes

A

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

28
Q

what lipid molecules are in liposomes

A

usually phospholipids with hydrophilic head groups and two hydrophobic chains

29
Q

how do liposomes reduce exposure at the edges

A

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

30
Q

what can liposomes carry

A

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

31
Q

what is phosphatidylcholine

A

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

32
Q

what determines the rigidity and permeability of the bilayer

A

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

33
Q

what determines stability of liposomes

A

lipid composition, storage condition, stabalisers

34
Q

what are the features of liposomes

A

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

35
Q

what are conventional liposomes

A

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

36
Q

what are sterically stabalised liposomes

A

carry hydrophilic coatings, used to obtain prolonged circulation times

37
Q

what are immunoliposomes

A

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

38
Q

what are cationic liposomes

A

positively charged and used for the delivery of genetic material

39
Q

what are conventional liposomes for

A

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

40
Q

how do long circulating liposomes work

A

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

41
Q

how do immunoliposomes work

A

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

42
Q

how do cationic liposomes work

A

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

43
Q

how toxic are liposomes

A

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

Respiratory Diseases & Dermatology (34 decks)

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