Silver oxynitrate gel formulation for enhanced stability and antibiofilm efficacy.

Autor: Spina CJ; Exciton Pharma Corp, Toronto, ON M5G 1L7, Canada. Electronic address: cspina@excitontech.com., Notarandrea-Alfonzo J; Exciton Pharma Corp, Toronto, ON M5G 1L7, Canada., Hay M; Exciton Technologies Incorporation, Edmonton, AB T5J 4P6, Canada., Ladhani R; Exciton Technologies Incorporation, Edmonton, AB T5J 4P6, Canada., Huszczynski S; University of Guelph, Guelph, ON N1G 2W1, Canada., Khursigara C; University of Guelph, Guelph, ON N1G 2W1, Canada., Precht R; Exciton Technologies Incorporation, Edmonton, AB T5J 4P6, Canada.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2020 Apr 30; Vol. 580, pp. 119197. Date of Electronic Publication: 2020 Mar 04.
DOI: 10.1016/j.ijpharm.2020.119197
Abstrakt: Topical semi-solid formulations are ubiquitous in personal care and pharmaceutical applications. For centuries, these topical formulations have facilitated delivery of active ingredients such as botanical oils, medicinal extracts and more recently antibiotics and biologics. Numerous strategies exist for the stabilization and release of these active ingredients from semi-solid formulations, namely, inclusion of anti-oxidants and surfactants to extend shelf life and facilitate delivery respectively. However, in the instance where the active ingredient itself is an oxidizing agent, traditional strategies for formulation have limited utility. Recent evidence has highlighted the exceptional efficacy and safety of highly oxidizing silver compounds, containing Ag 2+ and Ag 3+ . These higher oxidation states of silver provide antimicrobial and antibiofilm activity without impairing healing. However, as strong oxidizing agents, their application in medical device and pharmaceutical formulations such as semi-solid formulations are limited. The present study reports on the development of a silicone-based gel formulation of silver oxynitrate (Ag 7 NO 11 ), a higher oxidation state silver complex. In this study the chemical stability of silver oxynitrate was examined through solid state characterization with X-ray diffraction, formulation stability and microstructure of the semi-solid gel evaluated through various rheological techniques, therapeutic functionality of the semi-solid formulation investigated through in-vitro planktonic and biofilm antimicrobial studies, and biocompatibility assessed though in-vitro mammalian fibroblast and in-vivo porcine wound healing models. Enhanced stability of silver oxynitrate within the semi-solid formulation was observed over a four-month X-ray diffraction study. At the end of the study, silver oxynitrate was identified as the principal diffraction pattern in the semi-solid formulation where argentic oxide diffraction peaks were observed to be dominant in silver oxynitrate powders alone. Viscoelastic or gel-like behavior of the formulation was observed under dynamic rheological study where the storage modulus (G' = 1.77 ± 0.02 × 10 4 Pa) significantly exceeded the loss modulus (G″ = 4.89 ± 3.72 × 10 2 Pa) (p < 0.0001). No significant (p = 0.84) change was observed in the apparent viscous response within the last three months of the study period indicative that the formulation approached a steady rheological state. The silver oxynitrate semi-solid formulation provided sustained in-vitro antimicrobial activity (>99.99% kill) over seven days with a significant reduction in biofilm within 6 h (p < 0.001). In-vitro mammalian fibroblast studies demonstrated the formulation to be non-cytotoxic and 100% epithelialization was observed within a six-day in-vivo porcine deep partial-thickness wound. The improved chemical stability, biocompatibility and efficacy results indicate that silicone gel semi-solid formulation may be a promising medicinal configuration to facilitate expansion of the clinical use of silver oxynitrate.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Carla Spina, Roohee Ladhani, Michelle Hay, Johanny Notarandrea-Alfonzo and Rod Precht received payment in the form of salary as employees of Exciton Technologies Inc., for-profit biotechnology company.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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