Effect of the Incorporation of Functionalized Cyclodextrins in the Liposomal Bilayer

Abstract

Liposomes loaded with drug–cyclodextrin complexes are widely used as drug delivery systems, especially for species with low aqueous solubility and stability. Investigation of the intimate interactions of macrocycles with liposomes are essential for formulation of efficient and stable drug-in-cyclodextrin-in-liposome carriers. In this work, we reported the preparation of unilamellar vesicles of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) embedded with native β-cyclodextrin and two synthetic derivatives: heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMCD) and heptakis(2,3-di-O-acetyl)-β-cyclodextrin (DACD). We then studied the effect of these macrocycles on the liposomal size, membrane viscosity, and liposomal stability at different temperatures and concentrations. We observed that TMCD and DACD affected vesicle size and the change of size was related to CD concentration. Irrespective of its nature, the macrocycle established interactions with the phospholipidic head groups, preventing cyclodextrins to diffuse into the lipid bilayer, as confirmed by molecular dynamics simulations. Such supramolecular structuring improves liposome stability making these colloid systems promising carriers for biologically active compounds.

Chemosensitization of Temozolomide-Resistant Pediatric Diffuse Midline Glioma Using Potent Nanoencapsulated Forms of a N(3)-Propargyl Analogue

“…25 Recently, drug-incyclodextrin inclusion complexes have been encapsulated into nanoliposomes, consisting of one or more lipid bilayers enclosing an internal aqueous cavity, to provide a controlled drug release system. 26 This novel concept benefits accommodation of insoluble drugs in the aqueous core of nanoliposomes via cyclodextrins, thereby enhancing the incorporation rate and tempering drug−lipid membrane interaction and leakage out of liposomes. 27,28 We hypothesized that localized intratumoral delivery of TMZ-and N3P-loaded NPs via CED would bypass the BBB and provide wider distribution and longer residence time within the tumor interstitial space.…”

Nanocarriers for Biomedicine: From Lipid Formulations to Inorganic and Hybrid Nanoparticles

“…TM-β-CD and heptakis(2,3-di-O-acetyl)-β-CD (HDA-β-CD) were entrapped into unilamellar vesicles of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) [125]. The size of vesicles increased in proportion to the concentration of TM-β-CD and HDA-β-CD, while the size of the β-CD-loaded liposomal systems was not concentration-dependent.…”

Role of Calixarene in Chemotherapy Delivery Strategies

“…Consequently, these CDs have been shown to interact with cell membranes, reducing the activity of drug efflux pumps and conferring a powerful action against multidrug-resistant tumor cells [ 17 ]. In recent years, many studies have been performed to combine the benefits of cyclodextrins and liposomes by developing drug/cyclodextrin/liposome (DCL) inclusion complexes [ 18 , 19 , 20 , 21 ]. DCLs have been shown to improve the solubility of poorly water-soluble drugs such as paclitaxel, increasing their therapeutic efficacy in the treatment of multidrug-resistant tumors [ 22 ].…”