Colistin adorned topical nanoemulsion gel formulation for enhanced anti-microbial activity

The rising prevalence of severe skin infections, particularly those linked to multidrug-resistant (MDR) bacteria, poses an increasing public health challenge. Although the systemic administration of broad-spectrum antibiotics such as colistin sulfate (CS) represents a last-resort treatment for these infections, its use is associated with serious, life-threatening damage to vital organs. The current investigation aimed to develop and assess the efficacy of a CS-loaded nanoemulgel (NEG) as an anti-microbial therapy. Initially, a nanoemulsion (NE) was prepared using high speed homogenization, employing Labrafil as oil, Tween 80 as the surfactant and Transcutol as the co-surfactant. The formulation was then characterized for its pH, thermodynamic stability, particle size, drug content and entrapment efficiency. CS-NE formulation was then converted into CS-NEG using Carbopol 940 as a thickening agent. The resulting formulation was assessed for spreadability, viscosity, in-vitro drug release, ex-vivo skin permeation and antimicrobial activity. The particle size of the optimized CS-NE and CS-NEG formulations ranged from 193.2 ± 9.52 nm to 169.3 ± 10.22 nm and 274.9 ± 11.59 nm to 303.2 ± 20.36 nm, respectively, while the zeta potential of the developed CS-NE and CS-NEG formulations ranged from - 11.7 ± 0.11 mV to -42.3 ± 0.08 mV and - 11.8 ± 0.02 mV to -20.6 ± 0.51 mV, respectively. FTIR and thermal analysis (TGA/DSC) confirmed the absence of interactions between the drug and excipients. Both the CS-NE and CS-NEG formulations exhibited favorable physico-chemical properties suitable for transdermal applications. The drug content was within the official limits of ± 10%. pH of all formulations ranged from 5.6 ± 0.23 to 6.6 ± 0.56. The developed CS-NEG formulation exhibited relatively higher viscosity values ranged from 34,510 ± 99.85 cP to 38,810 ± 103.77 cP with excellent spreadability. The CS-NEG formulations achieved a cumulative drug release ranging from 73.6 ± 2.01% to 84.31 ± 5.28% over 24 h. Furthermore, these formulations demonstrated enhanced skin permeability following topical application and significantly improved antimicrobial activity (zone of inhibition = 21.23 mm) compared to CS solution. Overall, the findings suggest that the NE-based approach offers a promising therapeutic strategy for combating complex bacterial infections, including those caused by MDR pathogens.