One of the challenges in using a bone-spacer to cure infection is the fabrication of a material that can continuously release required antibiotics at effective concentrations for at least 4–6 weeks. Poly(methyl methacrylate) (PMMA) impregnated with antibiotics is one of the popularly used bone-spacer materials. Currently, improved sustained release of hydrophobic and hydrophilic antibiotics is needed for this material. Here, hydrophilic vancomycin (VAN) was encapsulated into calcium citrate (CC) particles and natural rice granules, and hydrophobic erythromycin (ERY) was encapsulated into ethyl cellulose and poly(lactic-co-glycolic acid) particles. The four antibiotic-loaded particles were each incorporated into the PMMA cement. The two unencapsulated drugs and all four drug-loaded particles distributed well in the obtained composites. PMMA composited with VAN-loaded CC showed prolonged VAN release at an effective concentration for more than 40 days, but the composite possessed lesser compressive strength than the PMMA with no drug. PMMA composited with unencapsulated ERY showed a better sustainment of drug release than those composited with encapsulated ERY. VAN elution from the VAN–CC–PMMA did not significantly affect the compressive strength of the material, whereas ERY elution from the ERY–PMMA composite significantly decreased the material’s mechanical strength.

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.