Protective Effect of Saccharides on Freeze-Dried Liposomes Encapsulating Drugs

Abstract

The production of freeze-dried liposomes encapsulating drugs is considered a key challenge since the drugs are prone to leakage. The aim of this work was to study the effect of different saccharides on preserving the stability and drug retention capacity of a previously developed liposomal formulation, when subjected to a freeze-drying process. The protective role of trehalose, lactose, glucose, mannitol and sucrose, known for their cryo/lyoprotective effect, was tested by addition of different concentrations to liposomes. Sucrose, in a concentration dependent manner (8:1 sugar:lipids mass ratio) proved to be a suitable cryo/lyoprotectant of these liposomes. Effectively, this saccharide prevents the fusion or/and aggregation of the liposomal formulation, protecting the integrity of the freeze-dried empty liposomes. The liposomal formulation containing sucrose was studied in terms of morphology, concentration, and anticancer drugs retention ability. The study involved two drugs encapsulated in the aqueous core, methotrexate (MTX) and doxorubicin (DOX), and one drug located in the lipid bilayer, tamoxifen (TAM). After the freeze-drying process, liposomes with sucrose encapsulating drugs revealed high physical stability, maintaining their narrow and monodisperse character, however high leakage of the drugs encapsulated in the aqueous core was observed. Otherwise, no significant drug leakage was detected on liposomes containing the TAM, which maintained its biological activity after the freeze-drying process. These findings reveal that sucrose is a good candidate for the cryo/lyoprotection of liposomes with drugs located in the lipid bilayer.

Influence of the Dispersion Medium and Cryoprotectants on the Physico-Chemical Features of Gliadin- and Zein-Based Nanoparticles

“…In addition, they prevent the formation of macroaggregates which entrap the carriers within a glassy matrix that reduces their mobility and promotes the formation of clusters (vitrification theory). This is also true in the case following the disruption and rearrangement of the tetrahedral structure of water (kosmotropic effect) [18]. The latter mechanism has been well documented for the disaccharide trehalose [19][20][21][22], but it is likely that a combination of all the aforementioned mechanisms can occur upon cryodesiccation [18].…”

“…Pharmaceutics 2022, 14, 332 2 of 18 Allouni and coworkers investigated the size of titanium dioxide nanoparticles in Roswell Park Memorial Institute (RPMI 1640) culture medium with and without 10% v/v of fetal bovine serum (FBS) or human serum albumin (0.01-1% w/w). It was observed that both the composition of the medium and its ionic strength influence the aggregation of the systems [7].…”

Controlled Differentiation of Mesenchymal Stem Cells into Hyaline Cartilage in miR-140-Activated Collagen Hydrogel

“…26 We then added carbohydrates as a lyoprotectant to shield the liposomes from aggregation and to preserve their integrity. 27 But, supplementing with sucrose during freeze-drying did not improve the liposome efficiency. Eventually, we pegylated the liposomes with Tocofersolan; a water-soluble, polyethylene glycol derivative of α-tocopherol, which successfully prevented the liposome aggregation and maintained their homogeneity.…”

New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats

“…As depicted in Figure 4, niosomal particles in dispersion form (A) as well as in freeze-dried form (B), appeared as nearly spherical particles with a smooth surface, indicating that the niosomal particles could conserve their physical form after preparation and freeze-drying. 48…”