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bioRxiv · 10.1101/2024.12.25.630303

Performance Evaluation of Ciprofloxacin loaded Micellar Bioconjugate Carrier for Eradication of Bacterial Biofilms

Gupta, C.·Ghosh, S. K.·Sen, R.
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Abstract

This study reports the utilization of a Curcumin-Exopolysaccharide (Cur-EPS) micellar bioconjugate comprising acid-labile ester bond as a carrier for ciprofloxacin (Cip) to improve its ability to eradicate mature bacterial biofilms. The most significant attributes of Cip-loaded Cur-EPS micelles, including hydrodynamic particle size, polydispersity index (PDI), and encapsulation efficiency (EE), were statistically optimized to be 305.43 {+/-} 1.47 nm, 0.38 {+/-} 1.23, and 84.50 {+/-} 2.01 %, respectively. At an acidic pH of 5.6, the pH-responsive release of Cip from Cur-EPS micelles was 82.51 {+/-} 2.95 % over a duration of 100 h, but it was reduced to 39.10 {+/-} 1.55 % at a pH of 7.4 over the same period. This pH-dependent Cip release may be attributed to the destabilisation of Cur-EPS micelles due to hydrolysis of the succinic acid linker in the acidic pH range. Thus, the acidic pH microenvironment of biofilms formed by pathogenic bacterial strains, such as methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, enhances the pH-responsive release of Cip from Cur-EPS micelles, thereby leading to the eradication of mature biofilms. This enhanced antibiofilm effect of Cip-Cur-EPS, in contrast to the free form of Cip, was evident from the significant decrease in the biofilm biomass. Furthermore, mature biofilms that formed on the surface of the urinary catheter were almost eradicated when treated in vitro with Cip-Cur-EPS for 72 h in the presence of artificial urine media (AUM). Moreover, Cip-Cur-EPS could also eradicate the biofilms formed by P. aeruginosa and MRSA in a catheterized bladder model employing recirculated artificial urine. Overall, this study demonstrated the antibiofilm potential of Cip-Cur-EPS micelles, rendering them suitable therapeutic agents for addressing biofilm-associated infections in clinical settings. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC="FIGDIR/small/630303v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@135f68org.highwire.dtl.DTLVardef@1dcd61forg.highwire.dtl.DTLVardef@16d9976org.highwire.dtl.DTLVardef@762425_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Gupta, C., Ghosh, S. K., Sen, R.. 2024-12-25. Performance Evaluation of Ciprofloxacin loaded Micellar Bioconjugate Carrier for Eradication of Bacterial Biofilms. https://doi.org/10.1101/2024.12.25.630303

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