Dual drug-loaded halloysite hybrid-based glycocluster for sustained release of hydrophobic molecules

Abstract

A dual drug-loaded HNT-CD glycocluster delivery system based on halloysite nanotubes and carbohydrate functionalized cyclodextrin was developed by a green protocol using solvent-free microwave irradiation.The nanohybrid was employed for concurrent load and release of silibinin and curcumin. The new delivery system was characterized by means of TGA, FT-IR spectroscopy, SEM and DLS. These techniques confirm the successful loading of the two drugs in the system. SEM and DLS measurements highlighted that the nanomaterial preserves a tubular structure with an average hydrodynamic radius of ca. 200 nm. The release of the drugs from the HNT glycocluster was investigated by means of UV-vis spectroscopy at two different pH values simulanting the typical physiological conditions of either gastric or intestinal fluids.Enzyme-linked lectin assays (ELLA) demonstrated that highly mannoside-cyclodextrins HNT entities display high affinity towards mannose selective ConA lectin. Biological assays showed that the new drug delivery system exhibits anti-proliferative activity against the investigated cell lines. Fluorescence microscopy confirmed ELLA results and it showed a high propensity of this drug delivery system to cross cell membranes and to penetrate into the cell nucleus. The results revealed that the synthesized multicavity system is a material of suitable size and nanoarchitecture to transport drugs into living cells.

Covalently modified halloysite clay nanotubes: synthesis, properties, biological and medical applications

“…Fluorescence microscopy images of the HNT-CD uptake by 8505C. The 8505C cell membrane (red) with co-localized HNT-CD (green) inside nuclei at 24 h. 27 …”

“…7). 27 However, because there are not biological mechanisms of aluminosilicate degradation in the body, halloysite is not biodegradable, and therefore it cannot be injected intravenously. The use of modified halloysite is limited as an active ingredient in external medical treatment with slow release of encapsulated drugs (e.g., in creams, implants, or wound treatment of tissues).…”

“…27 Also in this case, the novel nanomaterial was employed for the co-delivery of curcumin and silibinin. Release studies showed that pH deeply affects the kinetic course of the process, and at different pH values, indeed, a complementary behavior of drugs was observed.…”

“…Halloysite is proven to be a biocompatible material in several recent reports on cell cultures 24 and invertebrate models. 7 The uptake and toxic effects of halloysite have been investigated using human cell lines, namely breast cancer cells, 24 thyroid cancer cells, [25][26][27] hepatic cancer cells 28,29 and epithelial adenocarcinoma cells. 24 The toxicity of HNT was tested after 48 hours of incubation with fibroblast and human breast cells.…”

Synthesis and Characterization of Halloysite–Cyclodextrin Nanosponges for Enhanced Dyes Adsorption

“…7 Because of this peculiar chemical composition, the external surface of halloysite is easily functionalized by covalent grafting of silane groups which increases HNT application fields; moreover, the positively charged inner lumen allows for encapsulating negative-or electron-rich molecules. 8 HNTs have been used as filler for polymer 9 or hydrogel matrices, 10 drug carrier 11,12 and delivery, 13,14 and catalyst support, 15,16 as well as absorbents. 17,18 Recently, composite materials constituted by inorganic− organic hybrids have attracted considerable attention since they combine the organic and inorganic characteristics within a single molecular-scale composite.…”