Long-Term Storage of Lyophilized Liposomal Formulations

Abstract

Because aqueous liposomal formulations containing multiply unsaturated lipids are susceptible to chemical degradation, these formulations are often lyophilized. Despite their limited chemical stability, interest in the use of multiply unsaturated lipids to promote intracellular delivery has increased considerably in recent years. The goal of the current study was to examine the long term storage stability of lyophilized formulations containing lipids with increasing levels of unsaturation, and various strategies which can be employed to improve stability. Aqueous lipid-trehalose formulations containing 1,2-dilinolenoyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLinPC) or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) were lyophilized and stored at temperatures ranging from 4°C to 60°C. We observed that the lipid degradation rate increased as the storage temperature and unsaturation level were increased. Even the cleanest sugars which are available commercially contain iron contaminants, and it was observed that the chelation of these iron contaminants significantly improved the stability of DLPC during storage. However, the glass transition temperature of the sugar which was included in the formulation, the reduction of the oxygen in the aqueous sample prior to lyophilization, the inclusion of helper lipids (i.e., cholesterol), and the rate of freezing did not significantly improve stability.

Prebiotics as Protectants of Lactic Acid Bacteria

“…This protective capacity of sugars goes beyond the protection of microorganisms, as they are also able to protect other biomolecules (i.e., proteins, enzymes, liposomes) and pharmaceutical products (Oldenhof et al, 2005;Payton et al, 2014;Santivaragkna et al, 2008). ), leading cells to death.…”

Protective Effect of Saccharides on Freeze-Dried Liposomes Encapsulating Drugs

“…The potential of liposomes for specific therapeutic applications continues to be a challenge due to their inherent physical and chemical instability for long-term storage. Some of the problems include hydrolysis or oxidation of phospholipids, liposome aggregation or/and fusion, and increased bilayer permeability resulting in drug leakage (Payton et al, 2014;Porfire et al, 2017;Olusanya et al, 2018). A usual approach to overcome these problems is the production of a dry liposomal product.…”

Development of novel lipidic particles for siRNA delivery that are highly effective after 12 months storage

“…Previous studies have investigated the stability of dried-state liposomal preparations at different temperatures (i.e. 37 o C to 60 o C) over a 1-month period 19 , this is the first study to investigate the physiochemical and functional effects of the prolonged storage of lipoplexes over a longer period of time (i.e. 12 months) and at lower temperatures.…”