Temoporfin-in-Cyclodextrin-in-Liposome—A New Approach for Anticancer Drug Delivery: The Optimization of Composition

Abstract

The main goal of this study was to use hybrid delivery system for effective transportation of temoporfin (meta-tetrakis(3-hydroxyphenyl)chlorin, mTHPC) to target tissue. We suggested to couple two independent delivery systems (liposomes and inclusion complexes) to achieve drug-in-cyclodextrin-in-liposome (DCL) nanoconstructs. We further optimized the composition of DCLs, aiming to alter in a more favorable way a distribution of temoporfin in tumor tissue. We have prepared DCLs with different compositions varying the concentration of mTHPC and the type of β-cyclodextrin (β-CD) derivatives (Hydroxypropyl-, Methyl- and Trimethyl-β-CD). DCLs were prepared by thin-hydration technique and mTHPC/β-CD complexes were added at hydration step. The size was about 135 nm with the surface charge of (−38 mV). We have demonstrated that DCLs are stable and almost all mTHPC is bound to β-CDs in the inner aqueous liposome core. Among all tested DCLs, trimethyl-β-CD-based DCL demonstrated a homogenous accumulation of mTHPC across tumor spheroid volume, thus supposing optimal mTHPC distribution.

Cyclodextrin Based Nanoparticles for Drug Delivery and Theranostics

“…123 Some recent case studies of the CDs in the optimal drug delivery of drugs, proteins, peptides and aptamers are reported in the Table 3. [124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140] CDs can be moulded into various types of formulation for proving ease the drug delivery by diverse routes of administration.…”

Optical properties of photodynamic therapy drugs in different environments: the paradigmatic case of temoporfin

“…57 To overcome the mTHPC aggregation issue, specific drug delivery strategies are currently being pursued, 58 in particular, the use of molecular hosts based on beta-cyclodextrin (b-CD) has been proposed. 59,60 The incorporation of mTHPC into betacyclodextrin 61 (Fig. 1d) and its release in model lipid membranes 62,63 ( Fig.…”

Effect of the Incorporation of Functionalized Cyclodextrins in the Liposomal Bilayer

“…These systems are able to combine the capability of CDs to form CD/drug inclusion complexes with the use of liposomes as shuttle systems. Recently, different DCLs have been designed to overcome drawbacks such as the low solubility and low stability of many type of active compounds comprising aromatics, essential oils, and hydrophobic drugs [4,5,6,7,8,9,10,11,12,13].…”

“…DCLs combine the advantages of both carriers and thereby provide a controlled drug release [13,21,22,23]. The DCL system was applied to encapsulate a variety of lipophilic drugs [4,24,25].…”