Optimization of drug loading to improve physical stability of paclitaxel-loaded long-circulating liposomes

Abstract

The effect of formulation and process parameters on drug loading and physical stability of paclitaxel-loaded long-circulating liposomes was evaluated. The liposomes were prepared by hydration-extrusion method. The formulation parameters such as total lipid content, cholesterol content, saturated-unsaturated lipid ratio, drug-lipid ratio and process parameters such as extrusion pressure and number of extrusion cycles were studied and their impact on drug loading and physical stability was evaluated. A proportionate increase in drug loading was observed with increase in the total phospholipid content. Cholesterol content and saturated lipid content in the bilayer showed a negative influence on drug loading. The short-term stability evaluation of liposomes prepared with different drug-lipid ratios demonstrated that 1:60 as the optimum drug-lipid ratio to achieve a loading of 1-1.3 mg/mL without the risk of physical instability. The vesicle size decreased with an increase in the extrusion pressure and number of extrusion cycles, but no significant trends were observed for drug loading with changes in process pressure or number of cycles. The optimization of formulation and process parameters led to a physically stable formulation of paclitaxel-loaded long-circulating liposomes that maintain size, charge and integrity during storage.

Distinct solubility and cytotoxicity regimes of paclitaxel-loaded cationic liposomes at low and high drug content revealed by kinetic phase behavior and cancer cell viability studies

“…Figure 1h shows a low-magnification polarized optical micrograph displaying such crystals in an unsonicated CL PTXL sample 5 days after hydration. While previous studies have largely relied on multi-step HPLC experiments to monitor drug loading and retention over time [30,31,43], we set out to establish a DIC microscopy-based experimental protocol that would allow us to determine the PTXL stability in novel lipid formulations with higher throughput.…”

Structural characterization and biological fate of lactoferrin‐loaded liposomes during simulated infant digestion

“…A liposome, a self‐assembling and cell‐resembling delivery system with bilayer structure, could protect and control the release of bioactive components . With the unique properties of targeting, amphiphilicity and biodegradability, liposomes are widely used in agriculture, medicine and cosmetics industry . However, food‐grade liposomes haven't been broadly applied in food and nutrition areas due to the poor stability in the external environment (light, oxygen, and temperature) during storage and in the environment of the human gastrointestinal (GI) tract (pH, bile salts and enzymes), which can readily damage the membrane structure of liposomes leading to leakage of the entrapped ingredients .…”

“…1,2 With the unique properties of targeting, amphiphilicity and biodegradability, liposomes are widely used in agriculture, medicine and cosmetics industry. 3,4 However, food-grade liposomes haven't been broadly applied in food and nutrition areas due to the poor stability in the external environment (light, oxygen, and temperature) during storage and in the environment of the human gastrointestinal (GI) tract (pH, bile salts and enzymes), which can readily damage the membrane structure of liposomes leading to leakage of the entrapped ingredients. 5,6 Wall materials (mainly for phospholipids) oxidation is one of the crucial degradation pathways of these vesicles, and great attempts have been made to minimize the structural instability, such as using less unsaturated fatty acyl chain-containing phospholipids, 7 storing at low temperatures, 8 protecting liposomes from light and oxygen, 9 adding antioxidants and shielding the particles by surface coverage.…”

Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation

“…Loading PTX in saturated phosphatidylcholine (PC)-based liposomes was shown to worsen the situation (,1 mol%), owing to the higher membrane rigidity, which hinders the penetration of PTX into the hydrophobic domain of bilayers. 14,16 Moreover, PEGylation of liposomes aimed to extend the blood half-life of loaded PTX served a factor triggering the leakage of loaded PTX. [17][18][19] Liposomal PTX formulations that are currently on the market (Lipusu ) all use unsaturated PC (1,2-dioleoyl-snglycero-3-phosphocholine or EggPC) without PEGylated lipid supplementation, probably owing to these limitations in the stability of PTX-loaded liposomes.…”