The significance of drug-to-lipid ratio to the development of optimized liposomal formulation

Abstract

Liposomes are considered to be one of the most extensively investigated drug delivery nanosystems. Each drug can be loaded either in the liposomal hydrophilic core or within the lipidic bilayer and delivered eventually to the proper site into the organism. There are already many marketed approved liposomal products. The development of a liposomal product is a quite complicated process, while many critical parameters have to be investigated during the preparation process. The present study deals with the drug-to-lipid ratio (D/L ratio), which is a critical process parameter, expresses the actual capacity of the liposome to accommodate the drug and can play a key role at the optimization of every liposomal formulation. D/L ratio is affected by the composition, the different biomaterials and the loading method being used, so the improvement of D/L ratio can optimize the liposomal formulation. D/L ratio can be used as an index of the effectiveness of the preparation method too. Furthermore, D/L ratio influences the therapeutic efficacy of the liposomal product, expressing the actual dose of the drug being administrated. There is a variety of analytical methods, quantifying the drug and the lipids and estimating eventually the D/L ratio. According to the regulatory framework of nanomedicine, about the development of nanosimilars, D/L ratio is a necessary element for the nanosimilar product description and the statement of product comparability.

Development of Liposomal Vesicles for Osimertinib Delivery to EGFR Mutation—Positive Lung Cancer Cells

“…The passive loading is an equilibrium process dependent on parameters, such as the internal and external liposomal volume ratio, drug concentration and solubility in the hydration medium, amount of lipids used to prepare vesicles. The encapsulation efficacy is usually lower compared to remote/active loading [ 41 ]. OSI is encapsulated at higher loads, nearly 100% when prepared via active loading, irrespectively of PC type used ( Figure 2 A).…”

Development and Characterization of Liposomal Formulations Containing Phytosterols Extracted from Canola Oil Deodorizer Distillate along with Tocopherols as Food Additives

“…However, in case of the Mozafari method, B/L higher than 1:5 led to the appearance of visible white precipitate. Loading techniques along with the preparation procedures are found to influence drug/lipid ratio of liposomes [67]. In both thin film hydration homogenization and thin film hydration ultrasonication, hydrated bioactives-PC film is subjected to cavitation and shearing forces unlike the Mozafari method where less intense magnetic stirring is used during the loading process.…”

Encapsulated doxorubicin crystals influence lysolipid temperature-sensitive liposomes release and therapeutic efficacy in vitro and in vivo

“…For instance, Song et al, demonstrated efficient DOX loading into NTSLs using ammonium EDTA [24]. pH-gradient remote loading methods have been developed to stably and efficiently encapsulate anthracyclines (DOX, idarubicin or daunorubicin) into conventional liposomal formulations, such as Doxil  and Myocet ® [24], [33]. However, lower DOX loading capacity, with an optimum 20:1 lipid:DOX weight ratio, has often been reported when loading DOX into the LTSL formulation (ThermoDox  ) [9], [32], [34], [35].…”