Lipid based delivery system Flashcards
What are liposomes?
uni- or multi-lamellar, highly ordered concentric bilayer structures alternating with aqueous compartments
- hydrophilic head faces out in aqueous medium
hydrophobic tails face inwards
cholesterol
- is an excipient embedded between layers
- it is bulky/hydrophobic
= packs the bilayers more tightly and prevents leaking of drug
What are the classifications of liposomes?
are classified based on lamellae and size
Small Unilamellar Vesicles (SUV) – presence of one bilayer
Large Unilamellar Vesicles (LUV) - presence of one bilayer
Large Multilamellar Vesicles (MLV) – presence of more than one bilayer
Multivesicular vesicles (MVV) – presence of multiple vesicles within a large vesicle.
SUVs show a diameter of 60 to 100 nm.
LUVs, MLVs, and MVVs range in size from a few hundred nanometers to several microns
What are the characteristics of a bilayer?
hydrophilic solute is encapsulated in the aqueous core between the bilayer
hydrophobic solute has the affinity towards alkyl chains of the lipids/surfactants and would be embedded within the hydrophobic environment of bilayers
- lipid soluble drug would be embedded in the bilayer
bilayers could be PEGylated to achieve long circulation half-lives
- masks the liposomes presence thereby increasing circulation time and bioavailability
vesicles can be attached with antibodies to achieve a site-specific delivery.
What can liposomes be used for?
protection of encapsulated drug from premature degradation
reduction in side effects of the drug
potential to target the drug to a specific site in the body
relatively high payload at the site of action
increased shelf life, easier sterilization
potential to engineer surface characteristics
What is CPP? What is the CPP values molecules that form bilayers and amphiphiles (contain hydrophobic and hydrophilic groups)?
critical packing parameter
- shows the ability of molecules to form bilayer structures
molecules that form bilayers must have a value for CCP between 0.5 and 1
amphiphiles with a large head group area have CPP < 0.5 which promotes a micellar organisation in a hexagonal, H1 phase.
a small head group in comparison with the hydrophobic part of the molecules, CPP > 1, encourages an inverse structure, producing a hexagonal H2 phase.
What are H1 and H2 hexagonal lipid phases?
H1 - liposome (requires energy, is not spontaneously formed)
= has a lipid bilayer where there is hydrophilic head facing inwards, hydrophobic tails facing each other in a layer and hydrophilic heads facing outwards
= CPP < 0.5
H2 - micelle (forms spontaneously after reaching critical micellar concentration (CMC))
= has either hydrophilic head facing outwards and hydrophobic tails facing outwards or vice versa (inverted)
= CPP > 1
What are the methods of liposome preparation?
MLV – Lipid-hydration method, dehydration- rehydration method
LUV - Reverse phase evaporation method
SUV – Sonication, homogenization, ether injection method
What is phase transition temperature (Tc)?
temperature required to induce a change in the lipid physical state from the ordered gel phase, where the hydrocarbon chains are fully extended and closely packed, to the disordered liquid crystalline phase, where the hydrocarbon chains are randomly oriented and fluid.
in gel phase - there is both lipid chain conformational and translational order.
in the liquid crystalline phase - there exists a conformational and translational disorder with lateral diffusibility
What are the factors affecting vesicle size, encapsulation and release characteristics?
Solute
Lipid/surfactant characteristics & concentration
Cholesterol content
Surface charge
Method of preparation - SUV vs LUV vs MLV
Osmotic effect
What are the methods of controlling vesicle size?
Fractionation
- centrifugation
= vesicles sediment in a centrifugal field at a rate that relates to their size and density
= these differences in sedimentation rates can be exploited to separate vesicle populations of different sizes - size-exclusion chromatography
= is useful for separating SUV from larger ones
= as the vesicle suspension is run through the column, larger vesicles retain in the void volume, while the SUV are eluted.
What are the methods of controlling vesicle size?
Homogenisation/sonication
- high sheer homogenizers and probe sonicators are used to down size large vesicles.
What are the methods of controlling vesicle size?
Extrusion
- polycarbonate membrane extrusion
= is used to produce vesicles of defined size with a narrow size distribution
= based on the extrusion of a heterogeneous population of fairly large vesicles through polycarbonate membranes under pressure - ceramic extrusion
= passing the suspension through the ceramic membrane in an inside out direction thus maintaining the membrane in unclogged condition (unlike PME)
What is Caelyx? What is it used for? What are the benefits
Caelyx is doxorubicin HCl liposome injection
- is a sterile, translucent, red liposomal dispersion
are STEALTH® liposome carriers with a size ~100 nm.
- the surface of Caelyx® is PEGylated to achieve long circulation times in vivo and a ‘stealth’ character.
is used for the treatment of solid tumours including Kapsoi sarcoma, ovarian and breast cancer.
show passive targeting by preferential accumulation in tumours due to EPR effect.
What is the EPR effect?
enhanced permeation and retention effect (EPR)
- PEGylation of liposomes to achieve long circulation half-lives via increased circulation time and bioavailability
