Encapsulation of Curcumin-Loaded Liposomes for Colonic Drug Delivery in a pH-Responsive Polymer Cluster Using a pH-Driven and Organic Solvent-Free Process

Abstract

The present study aimed to develop and optimize liposome formulation for the colonic delivery of biologically active compounds. A strategy to facilitate such targeting is to formulate liposomes with a polymer coating sensitive to the pH shifts in the gastrointestinal tract. To this end, liposomes encapsulating curcumin—chosen as the biologically active compound model—and coated with the pH-responsive polymer Eudragit S100 were prepared and characterized. Curcumin was encapsulated into small unilamellar vesicles (SUVs) by the micelle-to-vesicle transition method (MVT) in a simple and organic solvent-free way. Curcumin-loaded liposomes were coated with Eudragit S100 by a fast and easily scalable pH-driven method. The prepared liposomes were evaluated for size, surface morphology, entrapment efficiency, stability, in vitro drug release, and curcumin antioxidant activity. In particular, curcumin-loaded liposomes displayed size lower than 100 nm, encapsulation efficiency of 98%, high stability at both 4 °C and 25 °C, high in vitro antioxidant activity, and a cumulative release that was completed within 200 min. A good Eudragit S100 coating which did not alter the properties of the curcumin-loaded liposomes was obtained. The present work therefore provides a fast and solvent-free method to prepare pH-responsive polymer-coated liposomes for the colonic delivery of biologically active compounds.

Eudragit S100 Entrapped Liposome for Curcumin Delivery: Anti-Oxidative Effect in Caco-2 Cells

“…In addition, the uploading of curcumin in liposomes gives rise to the formation of regions that differ from each other in terms of interactions and consequently do not melt at the same temperature [33]. DSC profile of Eu-Curc-liposome (Figure 3, blue curve) does not show any thermal transition in the investigated temperature range, confirming the already observed interaction between the polymer and liposomes [24]. A further investigation of these systems (data not shown) indicates that this pH-responsive polymer stabilizes curcumin loaded liposomes until 100 • C.…”

“…Vesicles for cell-based assays were sterilized with 0.2 µm sterile filters. Liposomes were encapsulated within Eudragit S100 using a pH-driven method as previously described [24]. Briefly, a 0.25% solution (w/w) of Eudragit S100 in a 100-mM alkaline phosphate buffer (pH 8.0) was prepared (Alkaline Solution).…”

“…Micrographs were recorded using a Jeol JEM-1011 microscope (Peabody, MA, USA) working at an accelerating voltage of 100 kV and acquired by an Olympus Quemesa Camera (11 Mpx). Samples were prepared as previously reported [24].…”

“…The zeta potential of these vesicles made of Lipoid S100 (i.e., mainly soy PC) and 20% (w/w) cholesterol, was around −7 mV, values in line with expectations for this type of vesicles. In order to obtain gastro-resistant vesicles, curcumin-loaded liposomes covered with Eudragit®(Eu-Curc-liposome) were obtained according to a recently described method [24], which allows to obtain clusters of vesicles covered with polymer capable of protecting liposomes and their payload from the acid compartments of the gastrointestinal tract. In acid environment, the obtained Eu-curc-liposomes showed micrometric dimensions with negative zeta potentials, as observed by other authors for methacrylic acid-methyl methacrylate (1:2) copolymer nanoparticles [29].…”

“…In this work, we loaded curcumin in the phospholipid bilayer of small unilamellar vesicles (SUVs, liposomes with diameter less than 80 nm) and we realized a gastroresistant polymeric coating around the liposomes through a previously developed procedure [24]. This allowed us to create a carrier, stable at the gastrointestinal level, capable of sequestering the curcumin within the hydrophobic double layer, protecting it from the degradation it would be subjected to in the biological environment, and conveying it inside the intestinal cells.…”