Liposome-based nanocarriers have emerged as a promising platform for targeted chemotherapy delivery in cancer treatment. These spherical vesicles, composed of lipid bilayers, can encapsulate both hydrophilic and hydrophobic drugs, offering improved pharmacokinetics and reduced systemic toxicity compared to conventional chemotherapy. The versatility of liposomes allows for precise engineering of their composition, surface properties, and drug-loading mechanisms to optimize therapeutic outcomes.

Lipid composition plays a critical role in determining the stability, drug encapsulation efficiency, and release kinetics of liposomal nanocarriers. The most commonly used lipids are phospholipids such as phosphatidylcholine, which form the bilayer structure, and cholesterol, which enhances membrane rigidity and reduces drug leakage. Saturated phospholipids like DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) provide higher stability, while unsaturated lipids offer greater flexibility. The choice of lipids affects the phase transition temperature, which in turn influences drug release rates at physiological temperatures.

Drug encapsulation methods for liposomes include passive loading techniques such as film hydration and reverse-phase evaporation, as well as active loading strategies like pH gradient and ammonium sulfate methods. Passive loading is suitable for hydrophobic drugs that integrate into the lipid bilayer or hydrophilic drugs trapped in the aqueous core. Active loading exploits transmembrane gradients to achieve high encapsulation efficiencies, particularly for weakly basic chemotherapeutic agents like doxorubicin. For instance, the pH gradient method can achieve encapsulation efficiencies exceeding 90% for drugs like doxorubicin by exploiting the difference between internal and external pH.

Surface modifications are employed to enhance liposome stability, circulation time, and targeting specificity. PEGylation, the covalent attachment of polyethylene glycol (PEG) chains to the liposome surface, creates a hydrophilic layer that reduces opsonization and extends circulation half-life from hours to days. Antibody conjugation enables active targeting by attaching ligands such as monoclonal antibodies or peptides to the liposome surface, facilitating receptor-mediated uptake in cancer cells. Common targeting moieties include anti-HER2 antibodies for breast cancer and folate for tumors overexpressing folate receptors.

Liposomes accumulate in tumors through both passive and active targeting mechanisms. The enhanced permeability and retention (EPR) effect drives passive accumulation, as leaky tumor vasculature allows liposome extravasation while impaired lymphatic drainage retains them in the tumor microenvironment. Active targeting enhances cellular uptake by binding to overexpressed receptors on cancer cells, increasing intracellular drug delivery. The combination of EPR and active targeting can improve tumor drug concentrations by 10 to 100-fold compared to free drugs.

Clinically approved liposomal formulations like Doxil exemplify the success of this technology. Doxil, a PEGylated liposomal doxorubicin, demonstrates prolonged circulation half-life (approximately 55 hours in humans) and reduced cardiotoxicity compared to free doxorubicin. Other liposomal drugs, such as DaunoXome (daunorubicin) and Onivyde (irinotecan), highlight the adaptability of liposomes for different chemotherapeutic agents. These formulations exhibit altered biodistribution, with reduced uptake in sensitive tissues like the heart and increased accumulation in tumors.

Pharmacokinetic benefits of liposomal nanocarriers include controlled drug release, decreased systemic toxicity, and improved therapeutic indices. The extended circulation time allows for less frequent dosing, while the EPR effect enhances tumor-specific delivery. However, challenges persist, such as drug leakage during circulation, which can lead to premature release and off-target effects. Immune recognition, particularly of PEGylated liposomes, can trigger accelerated blood clearance (ABC) upon repeated administration, reducing efficacy. Strategies to mitigate these issues include optimizing lipid composition, developing alternative stealth coatings, and employing stimuli-responsive release mechanisms.

Compared to polymeric nanoparticles, liposomes offer distinct advantages and limitations. Liposomes excel in biocompatibility and biodegradability due to their natural lipid components, whereas polymeric nanoparticles may exhibit longer-term toxicity concerns. However, polymeric nanoparticles often provide superior mechanical stability and higher drug-loading capacities for hydrophobic compounds. Liposomes are more prone to leakage but allow easier surface functionalization and faster drug release kinetics. The choice between liposome and polymeric nanocarriers depends on the specific drug properties, desired release profile, and therapeutic objectives.

Future advancements in liposome technology may involve multi-functional designs combining targeting ligands, stimuli-responsive release, and imaging agents for theranostic applications. Innovations in lipid chemistry and conjugation techniques will further enhance stability and targeting precision. Despite challenges, liposome-based nanocarriers remain at the forefront of nanomedicine for cancer therapy, offering a versatile and clinically validated approach to improving chemotherapy outcomes.