Natural Thermoresponsive Rice Granules as Biocompatible Drug Carriers

Abstract

Through thermal gravimetric, X-ray diffraction, infrared spectroscopy, and scanning electron microscopic analyses, here we reveal that the 4–5 μm diameter pentagonal shaped rice granules are surprisingly stable against α-amylase, trypsin, lipase, diluted acids, and diluted bases. Some papain-sensitive proteins play an important role in the granular shape stabilization. We employ the reversible thermoresponsive expansion/shrinking character in aqueous medium of this biopolymeric pentagonal granular assembly to encapsulate the antibiotic vancomycin into the granule at the drug loading content of 80% drug mass with only 20% rice granule mass. The obtained drug-loaded granules display no-burst but steady sustained release of the water-soluble vancomycin in an aqueous environment for more than 24 h.

Sustaining Antibiotic Release from a Poly(methyl methacrylate) Bone-Spacer

“…As reported earlier that RG is thermoresponsive, the granules can expand in an aqueous medium at high temperature and shrink back to their original size when cool . Unlike the medium, the VAN that had been taken up into the granules during the heat-induced granule expansion probably bound to the biopolymer matrix of the RG and could not move out from the granules during the cool down, resulting in an effective drug encapsulation into the RG.…”

“…The preparation of VAN-loaded RG or VAN−RG was carried out using the previously reported heat expansion method in which RG was incubated in VAN aqueous solution at 83 °C. 21 On the basis of the quantification of the free drug left in the water medium, the encapsulation process gave encapsulation efficiency of 70.2 ± 1.5% and the obtained 4.58 ± 0.84 μm granules possessed a VAN loading of 84.9 ± 0.3% (Figure 1A). It should be noted here that the encapsulation process did not change the morphology of the RGs; the shape was still polyhedral of multipentagonal faces with a similar average diameter to the original granules (data not shown).…”

“…As reported earlier that RG is thermoresponsive, the granules can expand in an aqueous medium at high temperature and shrink back to their original size when cool. 21 Unlike the medium, the VAN that had been taken up into the granules during the heat-induced granule expansion probably bound to the biopolymer matrix of the RG and could not move out from the granules during the cool down, resulting in an effective drug encapsulation into the RG. This speculation is supported by the disappearance of the endothermic peaks in the TGA profile of the RG (maximum at 298 °C) and that of the free VAN (broad peak with the maximum at 234 °C), and an appearance of a new broad peak with the peak maximum at 237 °C in the profile of VAN-RG (Figure S1A in the Supporting Information).…”

“…The broad endothermic peak likely represents various interactions between VAN and RG such as multiple hydrogen bondings between the two as previously speculated and illustrated. 21 IR spectrum of the VAN–RG also shows characteristic peaks of VAN, for example, a peak at 1638 cm –1 which corresponds to N–H bending, the 1600 and 1498 cm –1 absorption which corresponds to C=C stretching (in ring), and the peak at 1229 cm –1 which corresponds to C–O–C stretching (Figure S2A in the Supporting Information).…”

“…The hydrophilic VAN was successfully encapsulated into two different carriers, natural RGs and CC particles. The preparation of VAN-loaded RG or VAN–RG was carried out using the previously reported heat expansion method in which RG was incubated in VAN aqueous solution at 83 °C . On the basis of the quantification of the free drug left in the water medium, the encapsulation process gave encapsulation efficiency of 70.2 ± 1.5% and the obtained 4.58 ± 0.84 μm granules possessed a VAN loading of 84.9 ± 0.3% (Figure A).…”