Liposomes in Drug Delivery
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Direct answer
Liposomes are concentric phospholipid bilayers enclosing aqueous compartments, formed when amphiphilic lipids like egg or soy phosphatidylcholine hydrate and self-assemble; cholesterol at about 30-50 mole per cent stiffens the membrane above its phase transition temperature (dipalmitoyl phosphatidylcholine transitions near 41 degrees Celsius). Classification follows lamellarity and size: multilamellar vesicles above roughly 500 nanometres, large unilamellar vesicles in the 100-300 nanometre range and small unilamellar vesicles down to 20-100 nanometres, prepared by thin-film hydration (the Bangham method), extrusion, sonication or reverse-phase evaporation. Drugs load passively into the aqueous core or bilayer, or actively by a pH gradient — ammonium sulphate driving doxorubicin into pre-formed vesicles. Clinically, PEGylated liposomal doxorubicin exploits stealth chemistry and leaky tumour vasculature, while liposomal amphotericin B redirects a brutally nephrotoxic antifungal to the reticuloendothelial system and parasites within it — the basis of India's single-dose liposomal amphotericin policy for visceral leishmaniasis. Sterilisation is by 0.22 micrometre filtration only; heat destroys them.
What you must remember
- Structure: phospholipid bilayer vesicles; hydrophilic drugs load in the core, lipophilic drugs in the bilayer — one carrier serving both solubility problems.
- Types by lamellarity: MLV (many bilayers, over about 500 nm), LUV (single bilayer, roughly 100-300 nm), SUV (single bilayer, 20-100 nm); preparation by thin-film hydration, sonication, extrusion, reverse-phase evaporation or ethanol injection.
- Cholesterol role: 30-50 mole per cent abolishes gel-liquid transition leakage and stabilises the membrane in plasma — the single most quotable formulation fact.
- Phase transition: DPPC near 41 degrees Celsius; above Tc membranes leak, which is why liposomes are stored cool and never heat-sterilised.
- Active loading: a transmembrane pH or ion gradient (ammonium sulphate) concentrates weak bases like doxorubicin post-formation, giving high encapsulation efficiency.
- Stealth and targeting: PEGylation (Doxil-type) extends circulation and passively accumulates in tumours through leaky endothelium; ligand-grafted (folate, antibody) versions add active targeting.
- Market and programme anchors: liposomal amphotericin B, PEGylated doxorubicin and vincristine liposomes, plus the LNP descendants carrying siRNA and mRNA; India's kala-azar elimination programme adopted single-infusion liposomal amphotericin B at 10 mg/kg.
- Characterisation: size and polydispersity by dynamic light scattering, zeta potential, entrapment efficiency, in vitro release and residual solvent.
Why AmBisome changed leishmaniasis treatment
Conventional amphotericin B deoxycholate is cheap and effective but infuses misery — fever, rigors and cumulative nephrotoxicity — demanding weeks of monitored hospital treatment. Encapsulating the drug in small unilamellar liposomes changes its geography: the vesicles are swept up by reticuloendothelial macrophages of liver and spleen, exactly the compartments where Leishmania parasites hide, so the drug is delivered to the parasite's address while free drug exposure to kidney tubules collapses. That tissue logic allowed dose escalation impossible with the deoxycholate formulation and enabled the single 10 mg/kg infusion the Indian elimination programme favours, converting a month of toxicity into a day of supervised care. It is the cleanest teaching example that liposomes are a distribution technology, not just a delivery gadget.
Doxil tells the complementary story. PEGylation hides the vesicle from opsonins and macrophages, circulation extends to days, and vesicles extravasate through the leaky vasculature of tumours — the enhanced permeation and retention effect — raising tumour exposure while sparing the heart, dose-limiting for free doxorubicin. The price appears as palmar-plantar erythrodysaesthesia, a toxicity of the new distribution itself: redesigning where a drug goes redesigns which side effects you own. Both products are aseptically processed and 0.22 micrometre filtered, because terminal heat sterilisation is impossible for a structure defined by a phase transition near body-relevant temperatures.
Where students slip
Vesicle taxonomy is the first casualty: SUV, LUV and MLV describe lamellarity first and size second, and answers that classify purely by diameter lose the structural point. The second slip is calling liposomes "solubility enhancers" — they are carriers, and entrapment efficiency (per cent of drug actually inside) is the metric. Third, micelle versus liposome: micelles form above the critical micelle concentration from a single monolayer, while liposomes are bilayer-bounded aqueous spheres — a comparison guaranteed in vivas. Fourth, sterilisation: only filtration or aseptic processing is legitimate, with sterilising filtration validated at the viscosity used. Finally, know one transition temperature by number (DPPC, about 41 degrees Celsius) — it anchors the storage and stability discussion in physics.
Frequently asked questions
What are SUV, LUV and MLV in liposome terminology?
Small unilamellar (about 20-100 nm), large unilamellar (about 100-300 nm) and multilamellar (over 500 nm, many concentric bilayers) vesicles — classification by lamellarity that tracks size.
Why is cholesterol added to liposomal formulations?
At 30-50 mole per cent it fills membrane defects, abolishes the sharp phase transition and reduces drug leakage into plasma.
How does pH-gradient active loading work?
Liposomes preloaded with ammonium sulphate create an interior acidic compartment; neutral weak bases like doxorubicin cross the bilayer and become ion-trapped inside, concentrating to high encapsulation efficiency.
Why did liposomal amphotericin B transform kala-azar treatment?
Reticuloendothelial targeting concentrates drug in infected liver and spleen macrophages while sparing kidneys, enabling the single-dose 10 mg/kg infusion used in India's visceral leishmaniasis elimination programme.
How are liposomal products sterilised?
By validated 0.22 micrometre filtration and aseptic processing; heat sterilisation is impossible because bilayers disrupt above the phospholipid phase transition temperature.