Table 3.
Collection of the possible factors of critical quality attributes (CQAs) of liposomes.
| CQAs | Details | Comments |
|---|---|---|
| Type of liposomes | conventional liposomes | neutral or negative phospholipids |
| immune liposomes | antibodies, antibody fragments | |
| cationic liposomes | positive phospholipids | |
| magnetic liposomes | metal particles | |
| bioresponsive liposomes | thermosensitive (37 °C < Tm) | |
| pH-sensitive (acidic milieu) | ||
| LiPlasome (secretory phospholipase A2) | ||
| Number of lamellas | more layers | multilamellar (>0.5 µm) |
| oligolamellar (0.1–1.0 µm) | ||
| one layer | unilamellar | |
| Size of vesicle | small unilamellar vesicle (SUV) | 20–100 nm |
| medium-sized unilamellar vesicle (MUV) | between SUV and LUV, >100 nm | |
| large unilamellar vesicle (LUV) | >100 nm | |
| giant unilamellar vesicle (GUV) | >1 µm | |
| Surface modifications | no modification | rapid elimination |
| polyethylene glycol (PEG) chains (stealth liposomes) (quality and quantity of the chains) | steric exclusion (decreased opsonisation and phagocytosis); prolonged circulation | |
| monoclonal antibodies, antibody fragments, peptides, nucleic acids, carbohydrates, small molecules | provide targeted delivery by biding to the targeted receptors | |
| Morphology of liposomes | spherical vesicles | self-organised structure |
| concentric layers | multi-layered vesicles | |
| spherical with multiple non-concentric lipid vesicles inside | multivesicular liposome (MVL) | |
| Particle size and size distribution | d(0.1), d(0.5), d(0.9), span, surface weighted mean (D[3,2]), volume weighted mean (D[4,2]) | mean particle size should be under 200 nm; ideal around 100 nm |
| Polydispersity index (PdI) | indicating polydispersity of the system | below 0.5 is acceptable |
| Specific surface area (SSA) | influences drug release | smaller vesicles maintain higher surface area-to-volume ratio than the larger particles |
| Zeta potential | indicating stability | stable formulation around ±30 mV |
| Phase transition temperature (Tm) | influences drug release | determined by the composition of the liposome; cholesterols reduce the value |
| Empty liposomes/API content | modifies the physical attributes of the liposomes | the characteristics of the API determine its position |
| Position of the API | hydrophilic API | in the hydrophilic aqueous centre |
| lipophilic API | in the lipophilic double membrane | |
| surface-bounded | monoclonal antibodies, antibody fragments, peptides, nucleic acids, carbohydrates, small molecules | |
| Encapsulation efficiency (EE) | higher EE% is the goal to increase the drug concentration in the final formulation | manufacturing costs can be reduced, and more flexible dosing can be provided by higher EE% |
| Permeability | semi-permeable membrane | the highest permeability is at Tm; |
| targeted drug delivery | target specificity | increases effectiveness |
| Drug release profile | maintains therapeutic activity | site and timing can be modified |
| Sterility | if necessary | even for the materials |
| in the case of aseptic preparation | ||
| Stability | chemical, biological, microbiological | characteristic values must remain |
| in the recommended ranges until use |