Design of polyester structure in amphiphilic copolymer coated on magnetite nanoparticle: Effect on loading and sustaining release of indomethacin
Introduction
The magnetic responsive ability of magnetite nanoparticles (MNPs) with the use of external magnetic fields has recently attracted much attention for use in various biomedical applications [1,2] such as hyperthermia [3,4] and targeted drug delivery [5] for cancer diagnosis/treatment. These applications take advantages of specific properties of MNPs in nanoscale including their easy surface modification, exotic and superparamagnetic properties, nontoxic, biocompatibility and processability [6,7]. Particularly, the design of MNP surface with functional polymers has been prevalently studied for the development in drug delivery because coating MNPs with long chain polymers provided both steric repulsion stabilization and decorating versatility with functional groups on their surfaces [8], [9], [10]. Numerous methods have been used for coating polymers on MNP surface such as “grafting to” [11], “grafting from” [12,13], and emulsion [14,15], polymerizations as well as physical adsorption [16].
Interestingly, amphiphilic copolymers containing both hydrophilic and hydrophobic blocks are especially of interest for applications in drug delivery systems because they can molecularly self-assemble to form polymeric micelles in a selective solvent [17], [18], [19]. Previous works have presented the stabilization of MNPs with various types of amphiphilic polyester-containing copolymers such as poly(D,L-lactide-co-glycolide)-st-poly(ethylene glycol) (st-PLGA-PEG) copolymer [20], poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) copolymer [21] and cholesterol-grafted poly(ethylene glycol) methyl ether-Dlabile-poly(β-amino ester)-Dlabile-poly(ethylene glycol) methyl ether (mPEG-Dlabile-PAE-g-Chol) [22], in an attempt to obtain dispersible MNPs in water and potential uses for drug delivery. In aqueous system, hydrophobic drugs/molecules can hypothetically be embedded into hydrophobic polyester layers through physical adsorption, while hydrophilic moiety played a role in particle steric stabilization in water [23]. Aliphatic polyesters considered as hydrophobic portion have been generally prepared by two methods including the stepwise polycondensation and the ring-opening polymerization (ROP) of cyclic esters [24]. Especially, the stepwise polycondensation has been mostly used to prepare polyester from commercially available diol and dicarboxylic acid compounds [25] to obtain degradable and biocompatible polymers [26,27]. They can also be applied for hydrophobic drug reservoirs and also enhance cytotoxicity and cell viability of the drug [28,29].
This work focused in the design and synthesis of polyester-containing copolymer for coating on MNP surface and its potential applications for sustainable drug release. The copolymers were synthesized from the esterification of malonic acid, 1,6-hexane diol and mPEG with the molecular weight of 5000 g/mol [30]. Three types of the copolymers used in this work included mPEG-saturated polyester copolymer, mPEG-unsaturated polyester copolymer and mPEG-crosslinked polyester copolymer (Fig. 1). They were synthesized using a well-designed strategy to gain those with hydrophilic mPEG block and hydrophobic polyester block. Polyester parts can hypothetically be adsorbed on MNP surface, while hydrophilic mPEG moiety can serve as a stabilized outer layer to render good dispersibility for MNPs in aqueous media. In addition, the effect of polyester structures (saturated, unsaturated and crosslinked structures) coated on the MNP surface on loading and entrapment efficiencies as well as releasing behavior of entrapped indomethacin was investigated.
Section snippets
Materials
mPEG with the molecular weight of 5000 g/mol (Acros) was dried in vacuo before used. Iron(III) chloride anhydrous (FeCl3, Carlo Erba), iron(II) chloride tetrahydrate (FeCl2•4H2O, Carlo Erba), ammonium hydroxide (NH4OH, 28–30%, J.T. Baker), oleic acid (Fluka), malonic acid (99%, Acros), 1,6-hexane diol (99%, Acros) and maleic acid (99%, Acros) were used without purification. Potassium persulfate (KPS, K2S2O8) was kept in a dessicator until used.
Synthesis of mPEG-saturated polyester copolymer and mPEG-unsaturated polyester copolymer
mPEG (10.00 g, 2 mmol), malonic acid (4.78 g,
Results and discussion
The originality of this study was that we here demonstrated a design of polyester-containing copolymer coated on MNP surface for sustaining the release of an indomethacin model drug. Hypothetically, hydrophobic indomethacin was partially partitioned in the hydrophobic polyester on MNP surface, whereas hydrophilic mPEG offered steric repulsion stabilization and good water dispersibility to the particles. It was interesting to investigate the influence of saturated and unsaturated polyesters in
Conclusions
MNPs were surface modified with the copolymers containing hydrophobic polyester and hydrophilic mPEG to gain the particles with a rapid magnetic separation and good water dispersibility for use in drug sustainable release applications. Unsat-coated MNPs showed lower%EE and%DLE than those of sat-coated and crosslinked-coated MNPs, indicating that the structural design of the polymers can influence their drug entrapment and loading efficiencies. In addition, crosslinked-coated MNPs exhibited a
Declaration of Competing Interest
The authors declare no competing financial interest.
Acknowledgement
The authors acknowledge the financial support from the Thailand Research Fund (TRF) (RSA6280048) and the Research, Development and Engineering (RD&E) fund through the National Nanotechnology Center (NANOTEC), The National Science and Technology Development Agency (NSTDA), Thailand (Project P-10-10816) to Naresuan University. SP thanks the Royal Golden Jubilee PhD Program (PhD/0210/2556) for the scholarship.
References (34)
- et al.
Biomedical applications of magnetic nanoparticles
- et al.
Synthesis and characterization of magnetized- PEGylated dendrimer anchored to thermosensitive polymer for letrozole drug delivery
Colloid. Surface. B.
(2019) - et al.
Nanocarrier composed of magnetite core coated with three polymeric shells mediates LCS-1 delivery for synthetic lethal therapy of BLM-defective colorectal cancer cells
Biomacromolecules
(2018) - et al.
Chemical modification of magnetite nanoparticles and preparation of acrylic-base magnetic nanocomposite particles via miniemulsion polymerization
J. Magn. Magn. Mater.
(2017) Amphiphilic copolymers and their applications
Curr. Opin. Colloid. In.
(1996)- et al.
Magnetite nanoparticles stabilized with polymeric bilayer of poly(ethylene glycol) methyl ether-poly(ɛ-caprolactone) copolymers
Polymer
(2008) - et al.
Sustainable synthetic fibre production
A Brief Description of Textile fibers, Medical textile Materials
(2016)- et al.
Methoxy poly(ethylene glycol) and ε-caprolactone amphiphilic block copolymeric micelle containing indomethacin.II. Micelle formation and drug release behaviours
J. Control. Release
(1998) - et al.
Surfactant modification of aggregation-induced emission material as biocompatible nanoparticles: facile preparation and cell imaging
Nanoscale
(2013)