Kun Na1, You Han Bae. 1. Department of Materials Science and Engineering, Kwangju Institute of Science and Technology, Korea.
Abstract
PURPOSE: To investigate some physicochemical properties of self-assembled hydrogel nanoparticles of pullulan acetate (PA) and sulfonamide conjugates, as a potential tumor targeting drug carrier responsive to tumor extracellular pH. METHODS: A new class of pH-responsive polymers was synthesized by conjugating a sulfonamide, sulfadimethoxine (SDM), to succinylated pullulan acetate (coohPA). The polymers formed self-assembled PA/SDM hydrogel nanoparticles in aqueous media, which was confirmed by fluorometry and field emission-scanning electron microscopy. The pH-dependent behavior of the nanoparticles was examined by measuring transmittance, particle size and zeta potential. Adriamycin (ADR) was tested for loading into and release from the nanoparticles at various pHs. RESULTS: The mean diameters of all PA/SDM nanoparticles tested were <70 nm. with a unimodal size distribution. The critical aggregation concentrations at pH 9.0 were as low as 3.16 microg/mL. The nanoparticles showed good stability at pH 7.4, but shrank and aggregated below pH 7.0. The ADR release rate from the PA/SDM nanoparticles was pH-dependent around physiological pH and significantly enhanced below a pH of 6.8. CONCLUSIONS: The pH-responsive PA/SDM nanoparticles may provide some advantages for targeted anti-cancer drug delivery due to the particle aggregation and enhanced drug release rates at tumor pH.
PURPOSE: To investigate some physicochemical properties of self-assembled hydrogel nanoparticles of pullulan acetate (PA) and sulfonamide conjugates, as a potential tumor targeting drug carrier responsive to tumor extracellular pH. METHODS: A new class of pH-responsive polymers was synthesized by conjugating a sulfonamide, sulfadimethoxine (SDM), to succinylated pullulan acetate (coohPA). The polymers formed self-assembled PA/SDM hydrogel nanoparticles in aqueous media, which was confirmed by fluorometry and field emission-scanning electron microscopy. The pH-dependent behavior of the nanoparticles was examined by measuring transmittance, particle size and zeta potential. Adriamycin (ADR) was tested for loading into and release from the nanoparticles at various pHs. RESULTS: The mean diameters of all PA/SDM nanoparticles tested were <70 nm. with a unimodal size distribution. The critical aggregation concentrations at pH 9.0 were as low as 3.16 microg/mL. The nanoparticles showed good stability at pH 7.4, but shrank and aggregated below pH 7.0. The ADR release rate from the PA/SDM nanoparticles was pH-dependent around physiological pH and significantly enhanced below a pH of 6.8. CONCLUSIONS: The pH-responsive PA/SDM nanoparticles may provide some advantages for targeted anti-cancer drug delivery due to the particle aggregation and enhanced drug release rates at tumor pH.
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