What question did this study set out to answer?

This research aims to assess the stability of cholesterol-modulated liposomes under various physical and chemical stress conditions and their antimicrobial efficacy.

February 28, 2026Pharmaceuticals0 citationsOpen Access

Engineering Stability: Cholesterol-Modulated Liposome Response to Physical and Chemical Stressors for Enhanced Antimicrobial Activity

LRLuísa Morato Ribeiro CBCínthia Caetano Bonatto LSLuciano Paulino Silva

Puntos clave

This research aims to assess the stability of cholesterol-modulated liposomes under various physical and chemical stress conditions and their antimicrobial efficacy.
Subjected streptomycin-loaded liposomes to mechanical, thermal, and chemical stressors.
Measured hydrodynamic diameter, polydispersity index, and Zeta potential before and after stress exposure.
Conducted MIC assays against Escherichia coli and Staphylococcus aureus to evaluate antimicrobial activity.
Mechanical stress had no significant effects on liposome size or properties.
Combined ultrasound-freezing substantially increased liposome diameter and polydispersity.
1% SDS significantly reduced antimicrobial activity against E. coli, while some stressed formulations remained active.

Resumen

Background/Objectives: Liposomes are promising carriers for enhancing antibiotic delivery, but their stability under various stress conditions is crucial for clinical applicability. Methods: This study aimed to evaluate the physicochemical and antimicrobial stability of streptomycin-loaded liposomes subjected to mechanical (bath ultrasonication, probe ultrasonication, ultra-turrax homogenization), thermal (freezing, heating), and chemical (H2O2, Triton X-100, sodium dodecyl sulfate—SDS) stressors. Results: Isolated mechanical stresses (probe ultrasonication, ultrasonic bath, and ultra-turrax) did not significantly affect hydrodynamic diameter (DH), polydispersity index (PdI), or Zeta potential (ZP) (p > 0.05). In contrast, combined ultrasound–freezing stress induced marked destabilization, with DH increasing from ~110 nm to 362 nm (Lc0uf) and from 109 nm to 334 nm (Lc1uf), accompanied by PdI increases from ~0.13 to 0.37–0.41 and a ZP shift in Lc1uf from −43.1 mV to −60.1 mV. Thermal exposure at 75 °C and freezing at −30 °C caused no significant changes in DH or PdI, whereas freezing at −80 °C led to severe destabilization, with over fourfold increases in DH and fivefold increases in PdI; the cholesterol-free formulation (Lc0t−80) reached ~664 nm and a PdI of 0.609. Chemical oxidation with 1% H2O2 did not affect DH, PdI, or ZP, while surfactants (1% Triton X-100 and 1% SDS) significantly altered PdI and ZP in a cholesterol-dependent manner. MIC assays showed that formulations stressed by freezing at −80 °C or by combined ultrasound–freezing retained activity against Escherichia coli (MIC = 50 µg/mL), whereas SDS abolished activity. For Staphylococcus aureus, all stressed formulations remained active, and SDS reduced the MIC from 12.5 to 5.625 µg/mL. Conclusions: These findings demonstrate the robustness and stress-specific stabilization of these liposomal formulations, confirming that the antibiotic’s activity is preserved, which highlights their potential for therapeutic use.

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