The worrisome decline of antibiotic efficacy against Pseudomonas aeruginosa infections emphasizes the urgent need for new antibiotic delivery techniques. Liposomal formulations of tobramycin and ceftazidime were developedand comprehensively studied utilizing an active loading approach. Both formulations showed nanoscale size (<120 nm), low polydispersity index (<0.3), and spherical morphology, as validated by TEM examination. Tobramycin and ceftazidime encapsulation efficiency was in the rank of 20 %. Drug entrapment exploits both temperature change and electrostatic interaction between the charged drugs and lipids. The latter is demonstrated from Zeta potential shifts after drug integration. Tobramycin-loaded vesicles remained negatively charged (-22 mV), while ceftazidime-loaded vesicles remained positively charged (+22 mV), with magnitudes above ± 20 mV ensuring colloidal stability. In-vitro release experiments indicated temperature-dependent behavior, with rapid tobramycin release at 37 °C (∼71 % in 6 h) and sustained ceftazidime release (∼80 % over 48 h). Both showed slower release at 4 °C, indicating storage stability. Antimicrobial tests against P. aeruginosa PAO1 revealed significant improvements: liposomal tobramycin reduced MIC by 2.78-fold, and ceftazidime by 1.72-fold, compared to free antibiotic. Time-killing studies showed the liposomal formulations extended bactericidal action, which significantly reduced bacterial regrowth after 24 h at MIC values. Stability experiments conducted over three weeks revealed good colloidal stability, with minimal increases in size and PDI while retaining an absolute zeta potential. These findings imply that liposomal encapsulation of aminoglycosides and β-lactams increases antibacterial activity, prolongs therapeutic action, and provides stable nanoscale carriers, indicating their potential as advanced treatments against P. aeruginosa infections.

Liposomal tobramycin and ceftazidime as advanced nanocarriers against Pseudomonas aeruginosa infections

Silvia Pisani
;
Gabriele Trespidi;Rossella Dorati;Ida Genta;Silvia Buroni;Bice Conti.
2025-01-01

Abstract

The worrisome decline of antibiotic efficacy against Pseudomonas aeruginosa infections emphasizes the urgent need for new antibiotic delivery techniques. Liposomal formulations of tobramycin and ceftazidime were developedand comprehensively studied utilizing an active loading approach. Both formulations showed nanoscale size (<120 nm), low polydispersity index (<0.3), and spherical morphology, as validated by TEM examination. Tobramycin and ceftazidime encapsulation efficiency was in the rank of 20 %. Drug entrapment exploits both temperature change and electrostatic interaction between the charged drugs and lipids. The latter is demonstrated from Zeta potential shifts after drug integration. Tobramycin-loaded vesicles remained negatively charged (-22 mV), while ceftazidime-loaded vesicles remained positively charged (+22 mV), with magnitudes above ± 20 mV ensuring colloidal stability. In-vitro release experiments indicated temperature-dependent behavior, with rapid tobramycin release at 37 °C (∼71 % in 6 h) and sustained ceftazidime release (∼80 % over 48 h). Both showed slower release at 4 °C, indicating storage stability. Antimicrobial tests against P. aeruginosa PAO1 revealed significant improvements: liposomal tobramycin reduced MIC by 2.78-fold, and ceftazidime by 1.72-fold, compared to free antibiotic. Time-killing studies showed the liposomal formulations extended bactericidal action, which significantly reduced bacterial regrowth after 24 h at MIC values. Stability experiments conducted over three weeks revealed good colloidal stability, with minimal increases in size and PDI while retaining an absolute zeta potential. These findings imply that liposomal encapsulation of aminoglycosides and β-lactams increases antibacterial activity, prolongs therapeutic action, and provides stable nanoscale carriers, indicating their potential as advanced treatments against P. aeruginosa infections.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1539215
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