One-Pot Synthesis of Amphiphilic Biopolymers from Oxidized Alginate and Self-Assembly as a Carrier for Sustained Release of Hydrophobic Drugs

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.

A Review on Hydrophobically Associated Alginates: Approaches and Applications

“…The Ugi alginate derivative was synthesized using octylamine, oxidized sodium alginate, acetic acid, and tosylmethyl isocyanide (TOSMIC) and the formed amphiphilic derivative (Ugi-OSAOcT) self-assembled into stable micelles (CMC range of 0.30–0.085 mg/mL), within which the ibuprofen drug molecules were incorporated by dialysis. The drug loading capacity and encapsulation efficiency of the Ibuprofen loaded Ugi-OSAOcT micelles (IBU/Ugi-OSAOcT = 3:10) were as high as 10.9 ± 0.4–14.6 ± 0.3% and 40.8 ± 1.6–57.2 ± 1.3% (Table , Figures and ) …”

“…The drug loading capacity and encapsulation efficiency of the Ibuprofen loaded Ugi-OSAOcT micelles (IBU/Ugi-OSAOcT = 3:10) were as high as 10.9 ± 0.4–14.6 ± 0.3% and 40.8 ± 1.6–57.2 ± 1.3% ( Table 2 , Figures 11 and 12 ). 81 …”

“… One-pot synthesis of amphiphilic alginate derivative via Ugi reaction with octylamine as the primary amine. The Ugi-Alginate derivative is used for the encapsulation of ibuprofen, reproduced with permission from ( 81 ) under Creative Common Attribution (CC BY) license). …”

PET‐RAFT polymerization under flow chemistry and surface‐initiated reactions

“…The introduction of amphiphilic polymers in a suitable solvent can create self-assembled nanostructures with significant potential use in nanoreactors, 55 catalysts, 56 drug release 57 lengthy preparation time and low solid content, PISA usually only requires minutes to hours to complete the preparation, with the advantage of achieving high solid contents by dispersion or emulsion polymerization. 58 Although performing PISA in a batch may result in marked variations, 59 using a flow reactor capable of employing continuous polymerization may help reduce such variations and further increase the production rate.…”

“…The introduction of amphiphilic polymers in a suitable solvent can create self‐assembled nanostructures with significant potential use in nanoreactors, 55 catalysts, 56 drug release 57 and the like. Polymerization‐induced self‐assembly (PISA) has been developed to overcome the limitations of large‐scale preparation of nanostructures.…”