Silver sulfadiazine nanosuspension-loaded thermosensitive hydrogel as a topical antibacterial agent

Abstract

Background

Silver sulfadiazine (AgSD) is widely employed as an antibacterial agent for surface burn management. However, the antibacterial activity of AgSD was restrained because of the lower drug solubility and possible cytotoxicity.

Objective

This study aimed to formulate stable silver sulfadiazine/nanosuspensions (AgSD/NSs) with improved AgSD solubility and prepare a suitable carrier for AgSD/NS delivery. Nanotechnology was used to overcome the low drug dissolution rate of AgSD, while the new carrier loaded with AgSD/NS was assumed to decrease the possible cytotoxicity, enhance antibacterial activity, and promote wound healing.

Methods

AgSD/NSs were prepared by high pressure homogenization method. Poloxamer 407-based thermoresponsive hydrogels were prepared by cold method as carriers of AgSD/NS to obtain AgSD/NS-loaded thermoresponsive hydrogel. Scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) were used to measure the physicalchemical properties of AgSD/NSs and AgSD/NS-loaded gel. The cytotoxicity of the AgSD/NS-loaded gel was evaluated using methyl thiazolyltetrazolium assay with L929 mouse fibroblast cell lines. In vitro antibacterial activities of AgSD/NSs and AgSD/NS loaded gel were also measured.

Results

Stable AgSD/NSs with an average particle size of 369 nm were formulated while 1.5% P407 was selected as a stabilizer. The optimized AgSD/NS thermoresponsive hydrogel exhibited the gelation temperature of approximately 30°C. A significant improvement in solubility was observed for AgSD nanoparticles (96.7%) compared with AgSD coarse powders (12.5%). The results of FTIR and XRD revealed that the physicochemical properties of AgSD/NS were reserved after incorporating into the hydrogel. The cell viability after incubation with AgSD/NS-loaded thermoresponsive hydrogel improved from 60.7% to 90.6% compared with incubation with AgSD/NS directly. Drug release profiles from the thermoresponsive hydrogel increased compared with the commercial AgSD cream, implying less application frequency of AgSD cream clinically. In vitro antibacterial studies manifested that AgSD nanocrystallization significantly enhanced the antibacterial activity compared with the AgSD coarse powder.

Conclusion

The combination of AgSD nanosuspensions and thermoresponsive hydrogel effectively improved the AgSD antibacterial activity and decreased the cytotoxicity. This study also suggested that a poloxamer thermoresponsive hydrogel could be used as a delivery system for other nanocrystals to decrease possible nanotoxicity.

Keywords:

• cytotoxicity
• wound healing infection
• nanotechnology

Acknowledgments

This work has been funded by the Chinese National Science and Technology Key Projects (number 2016ZX09J16103-001-001). The authors thank Dr Zheng for technical assistance in the measurement of gelation temperature. They also thank Mr Liu Bo for helpful discussion during the manuscript writing.

Disclosure

The authors report no conflicts of interest in this work.