Abstract
In this paper, we developed an organic solvent-free, eco-friendly, simple and efficient one-pot approach for the preparation of amphiphilic conjugates (Ugi-OSAOcT) by grafting octylamine (OCA) to oxidized sodium alginate (OSA). The optimum reaction parameters that were obtained based on the degree of substitution (DS) of Ugi-OSAOcT were a reaction time of 12 h, a reaction temperature of 25 °C and a molar ratio of 1:2.4:3:3.3 (OSA:OCA:HAc:TOSMIC), respectively. The chemical structure and composition were characterized by Fourier transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance (1H NMR), X-ray diffraction (XRD), thermogravimetry analyser (TGA), gel permeation chromatography (GPC) and elemental analysis (EA). It was found that the Ugi-OSAOcT conjugates with a CMC value in the range of 0.30–0.085 mg/mL could self-assemble into stable and spherical micelles with a particle size of 135.7 ± 2.4–196.5 ± 3.8 nm and negative surface potentials of −32.8 ± 0.4–−38.2 ± 0.8 mV. Furthermore, ibuprofen (IBU), which served as a model poorly water-soluble drug, was successfully incorporated into the Ugi-OSAOcT micelles by dialysis method. The drug loading capacity (%DL) and encapsulation efficiency (%EE) of the IBU-loaded Ugi-OSAOcT micelles (IBU/Ugi-OSAOcT = 3:10) reached as much as 10.9 ± 0.4–14.6 ± 0.3% and 40.8 ± 1.6–57.2 ± 1.3%, respectively. The in vitro release study demonstrated that the IBU-loaded micelles had a sustained and pH-responsive drug release behavior. In addition, the DS of the hydrophobic segment on an OSA backbone was demonstrated to have an important effect on IBU loading and drug release behavior. Finally, the in vitro cytotoxicity assay demonstrated that the Ugi-OSAOcT conjugates exhibited no significant cytotoxicity against RAW 264.7 cells up to 1000 µg/mL. Therefore, the amphiphilic Ugi-OSAOcT conjugates synthesized by the green method exhibited great potential to load hydrophobic drugs, acting as a promising nanocarrier capable of responding to pH for sustained release of hydrophobic drugs.
Highlights
Polymer nanocarriers made from naturally occurring and biodegradable polymers have attracted much attention, especially in various drug delivery systems, since they offer a promising means by which to enhance the therapeutic values of drugs by improving their bioavailability, solubility and retention time, as well as benefitting patients due to lower cost and reduced toxicity [1–5]
Polymeric micelles are formed by amphiphilic block copolymers with hydrophilic and hydrophobic units, which can self-assemble in aqueous media above the critical micelle concentration (CMC) into unique and stable core-shell structures and are driven by a decrease in interfacial free energy [13,14]
Their hydrophobic core promotes the solubilization of water-insoluble drugs, protecting them from degradation by harsh environments, whereas their outer hydrophilic shell can reduce the binding of plasma proteins and minimize nonspecific uptake by the reticuloendothelial system (RES), prolonging their blood circulation time [15]
Summary
Polymer nanocarriers made from naturally occurring and biodegradable polymers have attracted much attention, especially in various drug delivery systems, since they offer a promising means by which to enhance the therapeutic values of drugs by improving their bioavailability, solubility and retention time, as well as benefitting patients due to lower cost and reduced toxicity [1–5]. One of the most naturally abundant anionic polysaccharides extracted from different species of marine brown algae and bacteria, have been extensively investigated and used for many biomedical and pharmaceutical applications, including drug delivery, encapsulation of enzymes and cells as well as wound healing management and tissue regeneration, due to its excellent biocompatibility, biodegradability, non-toxicity, relatively low cost, mild gelation by the addition of divalent cations (Ca2+), and the activity of carboxylic and hydroxyl groups [31–34]. They have already been granted permission from the U.S Food and Drug Administration (USFDA) for human use [35]. The results revealed that the amphiphilic Ugi-OSAOcT conjugates could have potential applications for effective entrapment and oral delivery of hydrophobic bioactive compounds
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