Inulin-based polymer coated SPIONs as potential drug delivery systems for targeted cancer therapy

Abstract

This paper deal with the synthesis and characterization of PEGylated squalene-grafted-inulin amphiphile capable of self-assembling and self-organizing into nanocarriers once placed in aqueous media. It was exploited as coating agent for obtaining doxorubicin loaded superparamagnetic iron oxide nanoparticles (SPIONs) endowed with stealth like behavior and excellent physicochemical stability. Inulin was firstly modified in the side chain with primary amine groups, followed in turn by conjugation with squalenoyl derivatives through common amidic coupling agents and PEGylation by imine linkage. Polymer coated SPIONs were so obtained by spontaneous self-assembling of inulin copolymer onto magnetite surface involving hydrophobic-hydrophobic interactions between the metallic core and the squalene moieties. The system was characterized in terms of hydrodynamic radius, zeta potential, shape and drug loading capacity. On the whole, the stealth-like shell stabilized the suspension in aqueous media, though allowing the release of the doxorubicin loaded in therapeutic range. The cytotoxicity profile on cancer (HCT116) cell line and in vitro drug uptake were evaluated both with and without an external magnetic field used as targeting agent and uptake promoter, displaying that magnetic targeting implies advantageous therapeutic effects, that is amplified drug uptake and increased anticancer activity throughout the tumor mass.

Inulin-Ethylenediamine Coated SPIONs Magnetoplexes: A Promising Tool for Improving siRNA Delivery

“…The dried pellet was dispersed in 2 mL of SDS solution (1.33 mg/mL) as stabilizer (14). The dispersion of SPIONs stabilized with SDS was added with gentile stirring to 50 mg of copolymer Inu-EDA and pH value was adjusted to 5.5 using HCl 0.1 N. The obtained mixture was sonicated in an ultrasonic bath for 10 min, thus diluted to 5 mL with double distilled water and incubated overnight.…”

“…Preparation of (IC-SPIONs)/siRNA Magnetoplexes Inu-EDA was synthesized as previously reported (14). Briefly, inulin dissolved in a-DMF, was activated by reacting with BNPC in a CEM Discover Microwave Reactor, for a 1 h with a power of 25 W. The reaction temperature was monitored and maintained at 60°C by cooling with external compressed air.…”

“…Comparing with other polysaccharides, to date inulin has been insufficiently explored as starting biomaterial for the development of drug delivery systems, although it shows peculiar advantageous properties, namely low molecular weight (~5000 Da), hydrophilicity, biocompatibility, and also the possibility to be easy functionalized in the side chain, obtaining derivatives with different potentialities (14), Thanks to these characteristics, inulin copolymers bearing primary amine groups in the side chain were recently synthesized by using the enhanced microwave synthesis (EMS) in order to combine the employment of this abundant and biocompatible macromolecules with the possibility to obtain safety polycations useful for siRNA delivery (15). Inulin may be an optimal candidate as starting biomaterial for the production of polycations for siRNA delivery, since low-molecular-weight polycations show less cytotoxicity and better nucleic acid unpackaging once inside cells (16).…”

“…During the last years, our group has optimized different polymer-coated super-paramagnetic iron oxide nanoparticles (SPIONs) proposed as carrier for magnetic drug delivery and targeting (11,13) and recently, an inulin based polymercoated magnetic nanocarrier has been studied as system able to improve the accumulation of doxorubicin into cancer cells in the presence of an external magnet, displaying a good magnetic targeting (14). Comparing with other polysaccharides, to date inulin has been insufficiently explored as starting biomaterial for the development of drug delivery systems, although it shows peculiar advantageous properties, namely low molecular weight (~5000 Da), hydrophilicity, biocompatibility, and also the possibility to be easy functionalized in the side chain, obtaining derivatives with different potentialities (14), Thanks to these characteristics, inulin copolymers bearing primary amine groups in the side chain were recently synthesized by using the enhanced microwave synthesis (EMS) in order to combine the employment of this abundant and biocompatible macromolecules with the possibility to obtain safety polycations useful for siRNA delivery (15).…”

Polyaminoacid–doxorubicin prodrug micelles as highly selective therapeutics for targeted cancer therapy

“…21 A derivatization degree in EDA of 21.4 mol% was obtained (DD EDA , related to PHEA monomer units). C 5 -Alkyne side chains were introduced into the PHEA-EDA backbone in aqueous environment and without adding catalysts.…”