Sprayable ciprofloxacin-loaded poloxamer hydrogels for wound infection treatment

Abstract

Topical antimicrobial treatments for severe burns and chronic wounds provide effective treatment against infections, but cause pain and discomfort with application. This study aimed to develop an antimicrobial topical formulation comprising thermoreversible poloxamers (Pluronic F127 and F68) and a broad-spectrum antimicrobial agent (ciprofloxacin hydrochloride, CH), that could be sprayed to eliminate application pain while maintaining antimicrobial activity. Formulations were characterized to determine their sprayability under cold conditions, gelation temperature, final storage modulus at skin temperature, drug release profile, ex vivo permeation through impaired porcine skin, and inhibition against common bacterial pathogens that colonize wounds. All cold formulations were sprayable from simple hand-held, pump-action sprayers due to their low viscosity. Upon heating, 17 and 20% Pluronic F127 formulations produced hydrogels eight to ten degrees below skin temperature, independent of ciprofloxacin loading. Increasing concentrations of Pluronic F127 increased the final storage modulus and viscosity of the gels, while inclusion of Pluronic F68 reduced these properties, showing that hydrogel rheological properties at skin temperature can be tuned via choice of formulation. Drug release was directly correlated to the rheological properties, with stiffer gels resulting in a decrease in drug release rate. Overall, gels released about 65-90% of their load within 12 hours. Ex vivo skin permeation demonstrated that drug was well retained in impaired porcine skin, which is desired to continuously treat bacteria localized to the wound. A well-diffusion assay indicated that the hydrogels had greater bacterial inhibition against Pseudomonas aeruginosa, Escherichia coli, and two strains of Staphylococcus aureus when compared to commercial controls. Overall, the results show the potential of CH-loaded poloxamer formulations as suitable sprayable topical dressings to deliver antimicrobials directly to wounds.

Keywords: antimicrobial; drug release; hydrogel; poloxamer; skin permeation; spray pattern.

Fig. 1.

Representative G’ curves of bare and CH-loaded formulations with increasing temperature of A) 17% F127 and B) 20% F127 base formulations.

Fig. 2.

Gelation temperature of bare and CH-loaded hydrogels. Reported as average ± standard deviation $(\mathrm{n}=3)$.

Fig. 3.

Representative viscosity curves of Pluronic formulations as a function of temperature (shear rate = 10 s⁻¹).

Fig. 4.

Cumulative drug release (%) from the A) 17% and B) 20% F127 and F127/F68 hydrogel bases. Inset images are the percent of CH released against time until 60% of the drug is released, which was used for kinetic modeling. Results reported are an average ± standard deviation $(\mathrm{n}=3)$.

Fig. 5.

The area measurements of inhibited growth for E. coli, P. aeruginosa, and two strains of S. aureus using the well diffusion method. Bare, 0.3%, and 0.5% CH-loaded hydrogels were compared to commercial controls. Averages ± standard deviation are reported (n=3).

Fig. 6.

The A) TEWL, B) cumulative mass permeated, and C) drug retained in the skin using the double-dermatome method from the permeation study. Average values ± standard deviation are reported (n≥3).

Fig. 7.

Analysis of the full spray patterns of bare and CH-loaded F127 formulations, including the major axis (A), minor axis (B), and ovality (C). Average values ± standard deviation are reported $(\mathrm{n}=3)$.

Fig. 8.

Analysis of the concentrated core of the spray pattern of bare and CH-loaded F127 formulations, including the major axis (A), minor axis (B), and ovality (C). Average values ± standard deviation are reported (n=3).

Fig. 9.

The area covered in the full spray (top) and core (bottom) patterns of bare and CH-loaded F127 formulations. Average values ± standard deviation are reported $(\mathrm{n}=3)$.

Fig. 10.

The %Core of the bare and CH-loaded F127 formulations spray patterns when sprayed from four, five, and six inches away from the target. Average values ± standard deviation are reported $(\mathrm{n}=3)$.