In Vitro Nephrotoxicity and Permeation of Vancomycin Hydrochloride Loaded Liposomes

Abstract

Drugs can be toxic to the fetus depending on the amount that permeates across the maternal–fetal barrier. One way to limit the amount which penetrates this barrier is to increase the molecular size of the drug. In this study, we have achieved this by encapsulating our model antibiotic (vancomycin hydrochloride, a known nephrotoxic agent) in liposomes. PEGylated and non-PEGylated liposomes encapsulating vancomycin hydrochloride were prepared using two different methods: thin-film hydration followed by the freeze–thaw method and the reverse-phase evaporation method. These liposomes were characterized by their hydrodynamic size and zeta potential measurements, CryoTEM microscopy, loading and encapsulation efficiency studies, in vitro release measurements and in vitro cytotoxicity assays using NRK-52 E rat kidney cells. We also determined the in vitro permeability of these liposomes across the human placental cell and dog kidney cell barriers. Vancomycin hydrochloride-loaded PEGylated liposomes (VHCL-lipo) of a size less than 200 nm were prepared. The VHCL-lipo were found to have the faster release of vancomycin hydrochloride and resulted in greater viability of NRK-52E cells. In vitro, the VHCL-lipo permeated the human placental cell and dog kidney cell barriers to a lesser extent than the free vancomycin hydrochloride. The data suggest a reduction in nephrotoxicity and permeability of vancomycin hydrochloride after encapsulation in PEGylated liposomes.

Impact of PEGylated Liposomal Doxorubicin and Carboplatin Combination on Glioblastoma

“…In addition, the results demonstrated that 89–93 and 100% of the standard DOX and CB were released from their relevant solutions after 2 and 2.5 h, respectively ( Figure 2 ), indicating the high efficacy of PEG-Lip-DOX, PEG-Lip-CB, PEG-Lip-DOX/CB, Lip-DOX, Lip-CB, and Lip-DOX/CB to control the drug release. Papp et al [ 42 ] also demonstrated that reversed-phase-synthesized PEGylated liposomes, compared to reversed-phase-synthesized non-PEGylated liposomes, caused a lower amount of drug release after 48 h (~20 vs. ~50%).…”

Enhancing the efficacy of letrozole-loaded PEGylated nanoliposomes against breast cancer cells: In vitro study

“…For the use of nanoparticles, premature drug release is a challenge that might be overcome by PEGylation [ 31 ]. In addition, Papp et al showed that PEGylated liposomes synthesized by the reverse phase method resulted in less drug release after 48 h than non-PEGylated liposomes synthesized by the reverse phase method [ 32 ].…”

Pharmacokinetic and Biomarker Quantification Studies on Vancomycin-Loaded PEGylated Liposomes and Its Potential to Reduce Vancomycin-Induced Kidney Injury: A Rat Study

“…In an effort to reduce vancomycin-induced nephrotoxicity, we have successfully encapsulated vancomycin in polyethylene glycol-coated liposomes (PEG-VANCO-lipo) [ 14 ]. The particle size of PEG-VANCO-lipo was found to be less than 200 nm, and they were characterized for stability, zeta-potential change, and in vitro release kinetics, as reported in our earlier publication [ 14 ].…”

“…In an effort to reduce vancomycin-induced nephrotoxicity, we have successfully encapsulated vancomycin in polyethylene glycol-coated liposomes (PEG-VANCO-lipo) [ 14 ]. The particle size of PEG-VANCO-lipo was found to be less than 200 nm, and they were characterized for stability, zeta-potential change, and in vitro release kinetics, as reported in our earlier publication [ 14 ]. We have previously carried out in vitro cytotoxicity studies on kidney cells (rat kidney epithelial cells, NRK-52E) using PEG-VANCO-lipo and found it to be minimally toxic compared to vancomycin alone [ 14 ].…”

“…The particle size of PEG-VANCO-lipo was found to be less than 200 nm, and they were characterized for stability, zeta-potential change, and in vitro release kinetics, as reported in our earlier publication [ 14 ]. We have previously carried out in vitro cytotoxicity studies on kidney cells (rat kidney epithelial cells, NRK-52E) using PEG-VANCO-lipo and found it to be minimally toxic compared to vancomycin alone [ 14 ]. Liposomes are phospholipid bilayer structures.…”