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Enhanced Antibacterial Efficacy and Topical Performance of a Levofloxacin Bilosomal Gel: In-Vitro Microbiological Outcomes and Rheological Suitability

Vol. 2 No. 3 (2025): Desember:

Karrar Sachit Salim (1), Ahmed Najim Abood (2), Ayad Almakki (3)

(1) College of Pharmacy, University of Basra, Iraq
(2) College of Pharmacy, University of Basra, Iraq
(3) College of Pharmacy, University of Basra, Iraq
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Abstract:

Skin and soft tissue infections (SSTIs) caused by Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae represent a growing clinical challenge due to increasing antimicrobial resistance and limitations of conventional topical therapies. Levofloxacin is an effective broad-spectrum fluoroquinolone; however, its topical efficacy is restricted by inadequate skin penetration and rapid drug loss at the application site. Nanovesicular carriers such as bilosomes have been proposed to enhance dermal drug delivery through improved stability and skin permeation. Limited studies have evaluated the physicochemical suitability and in-vitro antibacterial performance of levofloxacin-loaded bilosomal gels compared with conventional levofloxacin preparations. This study aimed to develop a levofloxacin bilosomal gel and evaluate its physicochemical properties and in-vitro antibacterial efficacy against common SSTI pathogens. Levofloxacin bilosomal gels exhibited skin-compatible pH (6.2–6.8), good spreadability, pseudoplastic rheological behavior, and uniform drug content (96.7–99.2%). In agar well-diffusion assays, bilosomal formulations (F1 and F2) produced significantly larger zones of inhibition than standard levofloxacin against E. coli, S. aureus, and K. pneumoniae at concentrations ≥32 µg/mL (p < 0.05), while no differences were observed at 0.5 µg/mL. Formulation F2 consistently demonstrated the highest antibacterial activity across all tested organisms. This study demonstrates enhanced antibacterial efficacy of levofloxacin through bilosomal encapsulation within a topical gel system. Levofloxacin bilosomal gel represents a promising topical delivery approach for improving local antibacterial efficacy in the management of skin and soft tissue infections.


Highlights



  1. Levofloxacin-loaded bilosomal gels exhibited skin-compatible pH, good spreadability, pseudoplastic rheology, and uniform drug content suitable for topical application.

  2. Bilosomal formulations significantly enhanced antibacterial activity against coli, S. aureus, and K. pneumoniae compared with standard levofloxacin at concentrations ≥ 32 µg/mL (p < 0.05).

  3. Formulation F2 consistently showed the highest antibacterial efficacy, highlighting bilosomes as a promising strategy to improve topical antibiotic performance.

References

[1] E. J. M. Monk, T. P. W. Jones, F. Bongomin, W. Kibone, Y. Nsubuga, et al., “Correction: Antimicrobial resistance in bacterial wound, skin, soft tissue and surgical site infections in Central, Eastern, Southern and Western Africa: A systematic review and meta-analysis,” PLOS Glob. Public Health, vol. 5, no. 5, p. e0004608, 2025, doi: 10.1371/journal.pgph.0004608.

[2] J. Lang, M. Shahata, and K. Melican, “Towards sustainable antimicrobial therapies for Staphylococcus aureus skin infections,” Sustain. Microbiol., vol. 1, no. 1, p. qvae023, 2024, doi: 10.1093/sumbio/qvae023.

[3] R. Davey and S. Tong, “The epidemiology of Staphylococcus aureus skin and soft tissue infection in the southern Barkly region of Australia’s Northern Territory in 2017,” Pathology, vol. 51, no. 3, pp. 308–312, 2019, doi: 10.1016/j.pathol.2018.11.010.

[4] J. Njenga, “Characterization of community-acquired methicillin-resistant Staphylococcus aureus isolated from patients with skin and soft tissue infections in selected health facilities, Kenya,” Open Forum Infect. Dis., vol. 10, no. 2, p. ofad500.1799, 2023, doi: 10.1093/ofid/ofad500.1799.

[5] J. Nyasinga, Z. Munshi, L. Musila, E. Mbugua, G. Omuse, and G. Revathi, “Low-level antibiotic resistance among Staphylococcus aureus and Gram-negative pathogens from infected skin and soft tissues in rural Kenya,” Open J. Med. Microbiol., vol. 14, pp. 23–38, 2024, doi: 10.4236/ojmm.2024.141003.

[6] J. Ziesmer et al., “Vancomycin-loaded microneedle arrays against methicillin-resistant Staphylococcus aureus skin infections,” Adv. Mater. Technol., vol. 6, no. 7, p. 2001307, 2021, doi: 10.1002/admt.202001307.

[7] C. Ferreira et al., “Clonal lineages, antimicrobial resistance, and PVL carriage of Staphylococcus aureus associated to skin and soft-tissue infections from ambulatory patients in Portugal,” Antibiotics, vol. 10, no. 4, p. 345, 2021, doi: 10.3390/antibiotics10040345.

[8] D. Mitrović et al., “The pharmaceutical and pharmacological potential applications of bilosomes as nanocarriers for drug delivery,” Molecules, vol. 30, no. 5, p. 1181, 2025, doi: 10.3390/molecules30051181.

[9] B. Sharma and I. Chauhan, “A review: Bilosomes as nanocarriers,” Curr. Nanomed., vol. 14, no. 3, pp. 178–187, 2023, doi: 10.2174/0124681873274362231110055846.

[10] D. Mondal, R. Mandal, and S. De, “Addressing the superior drug delivery performance of bilosomes—A microscopy and fluorescence study,” ACS Appl. Bio Mater., vol. 5, no. 8, pp. 3896–3911, 2022, doi: 10.1021/acsabm.2c00435.

[11] E. Waglewska, A. Pucek-Kaczmarek, and U. Bazylińska, “Self-assembled bilosomes with stimuli-responsive properties as a bioinspired dual-tunable nanoplatform for pH/temperature-triggered release of hybrid cargo,” Colloids Surf. B Biointerfaces, vol. 215, p. 112524, 2022, doi: 10.1016/j.colsurfb.2022.112524.

[12] D. Nayak, M. Rathnanand, and V. Tippavajhala, “Unlocking the potential of bilosomes and modified bilosomes: A comprehensive journey into advanced drug delivery trends,” AAPS PharmSciTech, vol. 24, p. 238, 2023, doi: 10.1208/s12249-023-02696-4.

[13] K. Aralelimath, J. Sahoo, and S. Wairkar, “Dermal drug delivery via bilosomes: A synergistic integration for better therapeutic outcomes,” J. Microencapsul., vol. 41, no. 8, pp. 818–831, 2024, doi: 10.1080/02652048.2024.2423618.

[14] R. Binsuwaidan et al., “Bilosomes as nanoplatform for oral delivery and modulated in vivo antimicrobial activity of lycopene,” Pharmaceuticals, vol. 15, no. 9, p. 1043, 2022, doi: 10.3390/ph15091043.

[15] L. Sabri and A. Khudhair, “Formulation and in-vitro evaluation of nanovesicles bilosomes loaded with ketoconazole,” Iraqi J. Pharm. Sci., vol. 34, no. 1, pp. 156–164, 2025, doi: 10.31351/vol34iss1pp156-164.

[16] S. Pattnaik, S. Priyadarshini, P. Niyogi, and L. Maharana, “Formulation and evaluation of microencapsulated levofloxacin gel,” [Journal unspecified], vol. 3, pp. 39–47, 2019.

[17] L. Salam, M. Abdelmottaleb, and A. Geneidi, “Formulation and characterization of proniosomal gels loaded with levofloxacin for dermal drug delivery,” Arch. Pharm. Sci. Ain Shams Univ., vol. 5, no. 2, pp. 288–303, 2021.

[18] E. M. Khaing et al., “Nitrocellulose for prolonged permeation of levofloxacin HCl–salicylic acid in situ gel,” Polymers, vol. 16, no. 7, p. 989, 2024, doi: 10.3390/polym16070989.

[19] S. Tayal et al., “Preparation and evaluation of diclofenac sodium loaded liposomal hydrogel in the treatment of rheumatoid arthritis,” Middle East J. Appl. Sci. Technol., vol. 7, no. 2, pp. 04–15, 2024.

[20] E. Tudoroiu et al., “Rheological characterization of some cellulose derivatives-based hydrogels,” in Proc. 9th Int. Conf. Adv. Mater. Syst., 2022, doi: 10.24264/icams-2022.ii.26.

[21] A. Shirkhedkar and S. Surana, “Quantitative determination of levofloxacin hemihydrate in bulk and tablets by UV-spectrophotometry and first-order derivative methods,” Pak. J. Pharm. Sci., vol. 22, no. 3, pp. 301–302, 2009.

[22] M. Balouiri, M. Sadiki, and S. K. Ibnsouda, “Methods for in vitro evaluating antimicrobial activity: A review,” J. Pharm. Anal., vol. 6, no. 2, pp. 71–79, 2016, doi: 10.1016/j.jpha.2015.11.005.

[23] Clinical and Laboratory Standards Institute (CLSI), Performance Standards for Antimicrobial Disk Susceptibility Tests, 13th ed., CLSI M02-A13, Wayne, PA, USA, 2023.

[24] A. Rusu et al., “Synthesis, characterization and antibacterial activity of a new derivative of levofloxacin,” J. Chil. Chem. Soc., vol. 65, no. 3, 2020, doi: 10.4067/s0717-97072020000204857.

[25] S. Lemmen et al., “Comparison of the bactericidal activity of moxifloxacin and levofloxacin,” Chemotherapy, vol. 49, pp. 33–35, 2003, doi: 10.1159/000069779.

[26] U. Navami et al., “Design and optimization of polyherbal gels for topical drug delivery by central composite statistical design,” Res. J. Pharm. Technol., vol. 17, no. 12, pp. 5702–5706, 2024, doi: 10.52711/0974-360X.2024.00868.

[27] S. Senarat et al., “Levofloxacin HCl-loaded Eudragit L-based in situ forming gel for periodontitis treatment,” Gels, vol. 9, no. 7, p. 583, 2023, doi: 10.3390/gels9070583.

[28] S. Galatage et al., “Design and characterization of camptothecin gel for treatment of epidermoid carcinoma,” Future J. Pharm. Sci., vol. 6, p. 50, 2020, doi: 10.1186/s43094-020-00066-6.

[29] A. Gawade, “Design and evaluation of emulgel with a polyherbal basis for topical delivery,” J. Med. Pharm. Allied Sci., vol. 14, no. 1, pp. 6929–6936, 2025, doi: 10.55522/jmpas.v14i1.6784.

[30] L. Gan, Y. Li, Y. Lv, and B. Zheng, “In vitro activity of levofloxacin against bacterial pathogens collected in China: A ten-year retrospective study,” medRxiv, preprint, 2020, doi: 10.21203/rs.3.rs-26208/v1.

[31] A. Firsov et al., “Comparative pharmacodynamics of moxifloxacin and levofloxacin,” J. Antimicrob. Chemother., vol. 46, no. 5, pp. 725–732, 2000, doi: 10.1093/jac/46.5.725.

[32] I. Odenholt and O. Cars, “Pharmacodynamics of moxifloxacin and levofloxacin,” J. Antimicrob. Chemother., vol. 58, no. 5, pp. 960–965, 2006, doi: 10.1093/jac/dkl356.