Nanocarriers are microscopic delivery vehicles that solve the problem of therapeutic agents being rapidly destroyed or eliminated before reaching target cells. These lipid-based systems shield fragile molecules, such as messenger RNA (mRNA) or chemotherapy drugs, from degradation by enzymes in the bloodstream. By protecting the payload, nanocarriers facilitate the transport of medicine to the site of action, significantly improving drug efficacy and patient outcomes. The two most prominent forms of these transporters are liposomes and lipid nanoparticles (LNPs), which differ fundamentally in their architecture and material components.
Structural and Compositional Differences
Liposomes are vesicular structures characterized by one or more concentric phospholipid bilayers, similar to a biological cell membrane. This lamellar structure creates an internal, centralized aqueous compartment ideal for encapsulating water-soluble (hydrophilic) drug payloads. The liposomal membrane, composed primarily of phospholipids and cholesterol, can also house fat-soluble (hydrophobic) drugs within its lipid layers.
In contrast, the modern Lipid Nanoparticle (LNP) possesses a non-lamellar, often amorphous or solid-like internal core formed by a specific combination of four lipid components. While both systems contain phospholipids and cholesterol, the defining feature of LNPs is the presence of an ionizable cationic lipid.
The LNP core structure involves the ionizable lipid binding electrostatically to a negatively charged nucleic acid, such as mRNA or small interfering RNA (siRNA), compacting it into an inverted micellar arrangement. LNPs also contain a PEGylated lipid (polyethylene glycol-conjugated lipid), which forms a protective outer layer that shields the particle from immune recognition and clearance.
How They Deliver and Perform
The difference in core architecture and lipid composition directly impacts the functional performance of these nanocarriers, particularly concerning their stability and mechanism of drug release. Traditional liposomes, with their fluid, bilayered membrane and aqueous core, are inherently prone to physical instability, which can lead to premature leakage or fusion in the bloodstream. The more compact, solid-like core structure of the LNP, reinforced by specific lipid ratios, provides enhanced colloidal stability and a longer shelf life for the encapsulated payload.
The most profound distinction lies in the mechanism of intracellular release, a process often termed “endosomal escape.” When a cell internalizes a nanocarrier, it is initially trapped within a small bubble called an endosome, which gradually acidifies. Liposomal cargo often relies on passive leakage or the pH-sensitivity of the drug itself to escape the endosome before it is degraded.
The ionizable lipids in LNPs remain neutrally charged at the body’s physiological pH of around 7.4, minimizing unwanted toxicity during circulation. Once the LNP is inside the endosome, the environment acidifies below pH 6.5, causing the ionizable lipids to become positively charged. This abrupt change in charge actively destabilizes the endosomal membrane, forcing it to rupture and allowing the nucleic acid payload to efficiently escape into the cell’s cytoplasm.
Current Clinical Usage
The distinct functional advantages of each system have channeled them toward different clinical applications. Liposomes have a long-standing history in medicine, primarily utilized for small-molecule chemotherapeutic agents. The encapsulation of drugs like doxorubicin in the liposomal product Doxil, first approved in 1995, extended the drug’s circulation time and reduced systemic toxicity.
Liposomes are commonly used to exploit the Enhanced Permeability and Retention (EPR) effect, where the nanocarriers passively accumulate in the leaky vasculature surrounding tumors. This mechanism focuses on delivering the drug to the general target area over an extended period.
In contrast, the LNP’s highly efficient, charge-driven endosomal escape mechanism makes it uniquely suited for delivering large, fragile genetic material that must reach the cell’s interior intact. LNPs enabled the rapid development and deployment of mRNA vaccines, such as those used for COVID-19, and are also used in approved siRNA therapeutics like Patisiran.