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Preparation and characterization of amphotericin B-loaded silk fibroin nanoparticles-in situ hydrogel composites for topical ophthalmic application

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Abstract

The objective of this study was to develop and characterize a novel combined systems of amphotericin B-loaded silk fibroin nanoparticles (AmB-FNPs) and in situ hydrogel for ocular administration. Three different formulations of AmB-FNPs were successfully prepared, by desolvation method, using polyethylenimine (PEI) or polyethylene glycol (PEG) as a coating polymer. All AmB-FNPs exhibited mean size of ~ 200 nm with narrow size distribution. The uncoated AmB-FNP and AmB-FNP-PEG were spherical in shape with zeta potential of ~  − 23 mV, whereas AmB-FNP-PEI exhibited cubic shape with zeta potential ~  + 36 mV. AmB was entrapped in FNPs in a partial aggregated form of AmB, which could reduce eye irritation compared to the marketed AmB deoxycholate. Then, AmB-FNPs were incorporated into two optimal thermosensitive in situ hydrogels; pluronic F127 (F127), and F127 and hyaluronic acid (F127/HA). All AmB-FNPs-in situ hydrogels exhibited homogeneous solutions with translucent light–yellow color, pH ~ 7, and osmolality of ~ 320–370 mOsmo/kg. At the ocular temperature, 35 °C, they manifested a pseudoplastic flow behavior and showed a rapid sol–gel transition within 30 s. In addition, the in vitro drug release studies showed an initial AmB burst release within 5 min. Finally, sterility test confirmed no microbial growth of all formulations. Overall results indicated that AmB-FNPs-in situ hydrogels showed satisfactory physicochemical properties as an ophthalmic formulations, which would reduce toxicity of AmB, increase precorneal residence time and improve patient compliance due to less frequent administration.

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Acknowledgements

This research was supported by the National Research Council of Thailand (NRCT) under the Royal Golden Jubilee Ph.D. program [Grant No. PHD/0160/2560]. The authors are thankful to Faculty of Pharmaceutical Sciences, Naresuan University for providing necessary facilities.

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  1. Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, 99 Moo 9 Amphoe Muang, Phitsanulok, 65000, Thailand

    Pratthana Chomchalao & Waree Tiyaboonchai

  2. Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand

    Nuttawut Saelim

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  1. Pratthana Chomchalao
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Chomchalao, P., Saelim, N. & Tiyaboonchai, W. Preparation and characterization of amphotericin B-loaded silk fibroin nanoparticles-in situ hydrogel composites for topical ophthalmic application. J Mater Sci 57, 12522–12539 (2022). https://doi.org/10.1007/s10853-022-07413-3

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