Nanoassemblies Based on Supramolecular Complexes of Nonionic Amphiphilic Cyclodextrin and Sorafenib as Effective Weapons to Kill Human HCC Cells

Abstract

Sorafenib (Sor), an effective chemiotherapeutic drug utilized against hepatocellular carcinoma (HCC), robustly interacts with nonionic amphiphilic cyclodextrin (aCD, SC6OH), forming, in aqueous solution, supramolecular complexes that behave as building blocks of highly water-dispersible colloidal nanoassemblies. SC6OH/Sor complex has been characterized by complementary spectroscopic techniques, such as UV-vis, steady-state fluorescence and anisotropy, resonance light scattering and (1)H NMR. The spectroscopic evidences and experiments carried out in the presence of an adamantane derivative, which competes with drug for CD cavity, agree with the entrapment of Sor in aCD, pointing out the role of the aCD cavity in the interaction between drug and amphiphile. Nanoassemblies based on SC6OH/Sor display size of ∼200 nm, negative zeta-potential (ζ = -11 mV), and both maximum loading capacity (LC ∼ 17%) and entrapment efficiency (EE ∼ 100%). Kinetic release profiles show a slower release of Sor from nanoassemblies with respect to the free drug. SC6OH/Sor nanoassemblies have very low hemolytic activity and high efficiency in vitro in decreasing cell growth and viability of HCC cell lines, such as HepG2, Hep3B, and PLC/PRF/5, opening promising chances to their in vivo applications.

A Molecular Dynamics Study of a Photodynamic Sensitizer for Cancer Cells: Inclusion Complexes of γ-Cyclodextrins with C70

“…Further simulations about the interaction of these amphiphilic complexes with a cell membrane model will be important in order to study the possible release of the hydrophobic fullerene solubilized in water thank to these amphiphilic systems. Finally, we also note that we considered only native CDs, while the use of covalently modified CDs is sometimes adopted, in order to achieve also the formation of supramolecular amphiphilic aggregates for the controlled drug delivery of hydrophobic drugs [13]. Such systems, their enhanced complex formation and their aggregation behavior will be considered in future work.…”

Understanding Surface Interaction and Inclusion Complexes between Piroxicam and Native or Crosslinked β-Cyclodextrins: The Role of Drug Concentration

“…Furthermore, the formation of drug/CD complex nanoparticles appears to increase the ability of CDs to enhance drug delivery through some mucosal membranes. Recently, chemically modified β-CD derivatives have been synthesized [ 9 , 10 , 11 , 12 , 13 , 14 ] and also theoretically studied [ 15 ] in order to improve cyclodextrin interactions with hydrophobic drugs and to enhance drug release through cell membranes. One of the possible modifications is to chemically bind aliphatic chains of different lengths on the primary or secondary CD rim in order to obtain amphiphilic cyclodextrins (aCD) [ 9 ].…”

“…Recently, chemically modified β-CD derivatives have been synthesized [ 9 , 10 , 11 , 12 , 13 , 14 ] and also theoretically studied [ 15 ] in order to improve cyclodextrin interactions with hydrophobic drugs and to enhance drug release through cell membranes. One of the possible modifications is to chemically bind aliphatic chains of different lengths on the primary or secondary CD rim in order to obtain amphiphilic cyclodextrins (aCD) [ 9 ]. This modification allows increasing the cyclodextrin interactions with biological membranes, improving their interaction with hydrophobic drugs, and inducing a higher self-assembly capacity in aqueous solutions compared to native β-CD [ 16 ].…”

Therapeutic Efficacy and Biodistribution of Paclitaxel-Bound Amphiphilic Cyclodextrin Nanoparticles: Analyses in 3D Tumor Culture and Tumor-Bearing Animals In Vivo

“…In addition, their dense hydroxyl display can be selectively functionalized to render an array of amphiphilic structures featuring spontaneous self-assembling capabilities in an aqueous environment, whose functional properties (i.e., stability, encapsulation capabilities, surface, interaction abilities, or environmental sensitivity) can be tailored. In fact, these nanodelivery systems were applied for the delivery of various anticancer drugs such as PCX [13][14][15], erlotinib [16], camptothecin [17][18][19], docetaxel [20], genistein [21], sorafenib [22], and quercetin/silibinin [23]. In addition, it has been preferred in studies to increase the effectiveness of various molecules besides anti-cancer drugs in different strategies such as gene silencing or phototherapy in cancer treatment [24][25][26][27][28][29][30].…”