P8: Formulation of Liposomes & Gels Flashcards
what are gels
viscoelastic solid-like materials comprised of an elastic cross-linked network and a solvent which is the major component
why does gel have a solid appearance
result of the entrapment and adhesion of the liquid in the large surface area of a solid 3D matrix
how is a solid matrix formed
cross-linking of the polymetric strands of macro molecu;es by physical or chemical forces
what are the characteristics of gel
large increase in viscocity above gel point
appearance of rubber-like elasticity
gel retains shape under low stress but deforms at higher stress
what are some examples of naturally occurring gelators
gelatin, collagen, agar, starch, gellan gum
what are the two classifications of gels derived from synthetic compounds
macromolecular (polymer)
supramolecular
what are the components of a gel
water (hydrogels) organic liquid (organogels)
what are some features of hydrogels
retain a significant amount of water
remains water-insoluble, used in topical drug delivery, soft contact lenses, implant coating
what determines the diffusion rate of a drug in a hydrogel
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
how does cross linking affect hydrogels
increases hydrophobicity of a gel
decreases the diffusion rate of the drug
what factors can change swelling characteristics of hydrogels and drug release
heat, pH, application of electrical current
results in responsive drug delivery - ‘on off’ switching mechanism
what causes a gel to become thermally irriversible
when gels are formed by strong chemical bonds
what causes a gel to be reversible
gels formed by weak non-covalent interactions (physical entanglements)
what are type 1 gels
irriversible systems
3D network formed by covalent bonds between macromolecules
formed by polymerisation of monomers of water soluble polymers in presence of cross-linking
what are type 2 gels
heat-reversible
held together by intermolecular bonds
gel on cooling below gel point
how are type 2 PVA solutions used
they have suitable gelling properties for topical skin applications
gel dries rapidly leaving plastic film with drug in intimate contact with skin
how are cross-linked polymetric systems formed
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
what are some applications of cross-linking polymetric systems
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
what does SAFIN stand for
self-assembled fibrillar networks
how are SAFINs formed
through self-aggregation of the small gelator molecules using non-covalent interactions
what are some examples of non-covalent interactions
H-bonding, pi-stacking, donor-acceptor interactions, metal coordination, solvophobic forces (hydrophobic forces for gels in water), Van der Waals
how are gels of low molecular mass compound formed
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
what are the three possible outcomes of low molecular compound gels being heated and cooled
- highly ordered aggregation giving rise to crystals
- random aggregation resulting in an amorphous precipitate
- aggregation process intermediate between these two, yielding a gel
what are some applications for supramolecular gels
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)
how are micelles formed
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
what happens at high micelle concentration
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
what are liposomes
vesicular structures based on one or more lipid bilayers encapsulating an aqueous core; considered as liquid capsules
what lipid molecules are in liposomes
usually phospholipids with hydrophilic head groups and two hydrophobic chains
how do liposomes reduce exposure at the edges
the bilayers self-close into one or more concentric compartments around a central discrete aqueous phase
can be multilamellar or unilamellar
what can liposomes carry
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
what is phosphatidylcholine
natural phospholipid as the major lipid component used in the preparation of pharmacuetical liposomes
what determines the rigidity and permeability of the bilayer
depends on the type and quality of lipids used
alkyl chain length and degree of unsaturation
presence of cholesterol can also increase rigidity
what determines stability of liposomes
lipid composition, storage condition, stabalisers
what are the features of liposomes
biologically inert, weakly immunogenic, low intrinsic toxicity, composed of natural phosphilipids
what are conventional liposomes
neural or negatively charged, generally used for passive targeting to the cells of mononuclear phagocyte systems
what are sterically stabalised liposomes
carry hydrophilic coatings, used to obtain prolonged circulation times
what are immunoliposomes
either conventional or sterically stabalised, used for active-targeting purposes
what are cationic liposomes
positively charged and used for the delivery of genetic material
what are conventional liposomes for
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
how do long circulating liposomes work
highly hydrated PEG group create a steric barrier against interactions with molecular and cellular components in the biological environment
how do immunoliposomes work
they have specific antibodies or antibody fragments on their surface to enhance target site binding
how do cationic liposomes work
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
how toxic are liposomes
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
