{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:01:00Z","timestamp":1771459260410,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T00:00:00Z","timestamp":1684886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MWU College of Pharmacy-Glendale campus intramural research faculty"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Vancomycin is a commonly used antibiotic in hospital settings, especially against Methicillin-resistant staphylococcus aureus (MRSA). One of the major adverse events of vancomycin use in adults is kidney injury. The drug concentration, specifically the area under the concentration curve, predicts kidney injury in adults receiving vancomycin. To attempt to reduce vancomycin-induced nephrotoxicity, we have successfully encapsulated vancomycin in polyethylene glycol-coated liposomes (PEG-VANCO-lipo). We have previously carried out in vitro cytotoxicity studies on kidney cells using PEG-VANCO-lipo and found it to be minimally toxic compared to the standard vancomycin. In this study, we have dosed male adult rats with PEG-VANCO-lipo or vancomycin HCl and compared plasma vancomycin concentrations and KIM-1 as an injury biomarker in rat urine. Male Sprague Dawley rats (350 \u00b1 10 g) were administered vancomycin (n = 6) or PEG-VANCO-lipo (n = 6) 150 mg\/kg\/day for three days using an IV infusion in the left jugular vein catheter. Blood was collected for plasma at 15, 30, 60, 120, 240, and 1440 min after the first and the last IV dose. Urine was collected 0\u20132, 2\u20134, 4\u20138, and 8\u201324 h after the first and the last IV infusions using metabolic cages. The animals were observed for three days after the last compound administration. Vancomycin was quantified in plasma by LC-MS\/MS. Urinary KIM-1 analysis was done by using an ELISA kit. Three days after the last dose, under terminal anesthesia with IP ketamine (65\u2013100 mg\/kg) and xylazine (7\u201310 mg\/kg), rats were euthanized. Vancomycin urine and kidney concentrations and KIM-1 were lower on day three in the PEG-Vanco-lipo group compared to the vancomycin group (p &lt; 0.05, ANOVA and\/or t-test). There was a significant reduction in plasma vancomycin concentration on day one and day three (p &lt; 0.05, t-test) in the vancomycin group compared to the PEG-VANCO-lipo group. Vancomycin-loaded PEGylated liposomes resulted in lower levels of kidney injury, as noted by a decrease in KIM-1 values. Moreover, longer circulation in plasma with increased concentration in plasma as opposed to the kidney was observed with the PEG-VANCO-lipo group. The results indicate the high potential of PEG-VANCO-lipo in decreasing the nephrotoxicity of vancomycin clinically.<\/jats:p>","DOI":"10.3390\/pharmaceutics15061582","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T01:36:28Z","timestamp":1684978588000},"page":"1582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacokinetic and Biomarker Quantification Studies on Vancomycin-Loaded PEGylated Liposomes and Its Potential to Reduce Vancomycin-Induced Kidney Injury: A Rat Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0280-0349","authenticated-orcid":false,"given":"Medha D.","family":"Joshi","sequence":"first","affiliation":[{"name":"College of Pharmacy, Midwestern University, Glendale Campus, 19555 N. 59th Avenue, Glendale, AZ 85308, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulina","family":"Iacoban","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Midwestern University, Glendale Campus, 19555 N. 59th Avenue, Glendale, AZ 85308, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1091-6130","authenticated-orcid":false,"given":"Marc H.","family":"Scheetz","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Midwestern University, Downers Grove Campus, 555 31st Street, Downers Grove, IL 60515, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1093\/cid\/ciq146","article-title":"Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children","volume":"52","author":"Liu","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.14740\/wjnu384","article-title":"Methicillin-Resistant Staphylococcus aureus Infections in Patients with Renal Disorders: A Review","volume":"8","author":"Singh","year":"2019","journal-title":"World J. Nephrol. Urol."},{"key":"ref_3","first-page":"459","article-title":"The Nephrotoxicity of Vancomycin","volume":"102","author":"Filippone","year":"2017","journal-title":"Clin. Pharm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1002\/phar.2388","article-title":"Vancomycin-Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention","volume":"40","author":"Pais","year":"2020","journal-title":"Pharmacotherapy"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tsutsuura, M., Moriyama, H., Kojima, N., Mizukami, Y., Tashiro, S., Osa, S., Enoki, Y., Taguchi, K., Oda, K., and Fujii, S. (2021). The monitoring of vancomycin: A systematic review and meta-analyses of area under the concentration-time curve-guided dosing and trough-guided dosing. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-05858-6"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"F517","DOI":"10.1152\/ajprenal.00291.2005","article-title":"Urinary kidney injury molecule-1: A sensitive quantitative biomarker for early detection of kidney tubular injury","volume":"290","author":"Vaidya","year":"2006","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e01945-20","DOI":"10.1128\/AAC.01945-20","article-title":"The Pharmacodynamic-Toxicodynamic Relationship of AUC and Cmax in Vancomycin-Induced Kidney Injury in an Animal Model","volume":"65","author":"Avedissian","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00416-17","DOI":"10.1128\/AAC.00416-17","article-title":"24-Hour Pharmacokinetic Relationships for Vancomycin and Novel Urinary Biomarkers of Acute Kidney Injury","volume":"61","author":"Rhodes","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00079-19","DOI":"10.1128\/AAC.00079-19","article-title":"Comparative Performance of Urinary Biomarkers for Vancomycin-Induced Kidney Injury According to Timeline of Injury","volume":"63","author":"Pais","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1080\/00365510802145059","article-title":"Kidney Injury Molecule-1 (KIM-1): A specific and sensitive biomarker of kidney injury","volume":"241","author":"Bonventre","year":"2008","journal-title":"Scand. J. Clin. Lab. Investig. Suppl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1046\/j.1523-1755.2002.00433.x","article-title":"Kidney Injury Molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury","volume":"62","author":"Han","year":"2002","journal-title":"Kidney Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s12967-021-02776-8","article-title":"The value of kidney injury molecule 1 in predicting acute kidney injury in adult patients: A systematic review and Bayesian meta-analysis","volume":"19","author":"Geng","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_13","first-page":"1219","article-title":"Understanding kidney injury molecule 1: A novel immune factor in kidney pathophysiology","volume":"11","author":"Song","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Papp, N., Panicker, J., Rubino, J., Pais, G., Czechowicz, A., Prozialeck, W.C., Griffin, B., Weissig, V., Scheetz, M., and Joshi, M.D. (2022). In Vitro Nephrotoxicity and Permeation of Vancomycin Hydrochloride Loaded Liposomes. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14061153"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/jac\/49.suppl_1.37","article-title":"Amphotericin B nephrotoxicity","volume":"49","author":"Deray","year":"2002","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/jac\/49.suppl_1.21","article-title":"AmBisome: Liposomal formulation, structure, mechanism of action and pre-clinical experience","volume":"49","author":"Proffitt","year":"2002","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.2147\/IJN.S130125","article-title":"Tat-functionalized liposomes for the treatment of meningitis: An in vitro study","volume":"12","author":"Shi","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.ijpharm.2015.08.085","article-title":"Chitosan coated vancomycin hydrochloride liposomes: Characterizations and evaluation","volume":"495","author":"Yang","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1021\/acsinfecdis.9b00232","article-title":"Preserving the Efficacy of Glycopeptide Antibiotics during Nanoencapsulation in Liposomes","volume":"5","author":"Xu","year":"2019","journal-title":"ACS Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rukavina, Z., and Vani\u0107, \u017d. (2016). Current Trends in Development of Liposomes for Targeting Bacterial Biofilms. Pharmaceutics, 8.","DOI":"10.3390\/pharmaceutics8020018"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.actbio.2019.12.014","article-title":"Encapsulation of collagen mimetic peptide-tethered vancomycin liposomes in collagen-based scaffolds for infection control in wounds","volume":"103","author":"Thapa","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1093\/jac\/dks212","article-title":"Liposomal encapsulation of vancomycin improves killing of methicillin-resistant Staphylococcus aureus in a murine infection model","volume":"67","author":"Sande","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.3389\/fphar.2019.01401","article-title":"Fusogenic Liposomes Increase the Antimicrobial Activity of Vancomycin Against Staphylococcus aureus Biofilm","volume":"10","author":"Scriboni","year":"2019","journal-title":"Front. Pharm."},{"key":"ref_24","first-page":"153","article-title":"The bactericidal effect of liposomal vancomycin as a topical combating system against Methicillin-resistant Staphylococcus aureus skin wound infection in mice","volume":"33","author":"Hajiahmadi","year":"2019","journal-title":"Med. J. Islam. Repub. Iran."},{"key":"ref_25","first-page":"636743","article-title":"Development and Stability Studies of Novel Liposomal Vancomycin Formulations","volume":"2012","author":"Muppidi","year":"2012","journal-title":"ISRN Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4537","DOI":"10.1128\/AAC.00713-11","article-title":"PEGylated Liposome Encapsulation Increases the Lung Tissue Concentration of Vancomycin","volume":"55","author":"Muppidi","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ijantimicag.2010.10.011","article-title":"Preparation of liposomal vancomycin and intracellular killing of meticillin-resistant Staphylococcus aureus (MRSA)","volume":"37","author":"Pumerantz","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"205","DOI":"10.2174\/157489112803521904","article-title":"PEGylated liposomal vancomycin: A glimmer of hope for improving treatment outcomes in MRSA pneumonia","volume":"7","author":"Pumerantz","year":"2012","journal-title":"Recent. Pat. Antiinfect. Drug Discov."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.eurpolymj.2004.10.031","article-title":"Light scattering studies of stereocomplex formation of stereoregular poly(methyl methacrylate) in solutions","volume":"41","author":"Zhao","year":"2005","journal-title":"Eur. Polym. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/cts.12484","article-title":"High-Performance Liquid Chromatography Method for Rich Pharmacokinetic Sampling Schemes in Translational Rat Toxicity Models with Vancomycin","volume":"10","author":"Joshi","year":"2017","journal-title":"Clin. Transl. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"106583","DOI":"10.1016\/j.ijantimicag.2022.106583","article-title":"A translational rat model to assess glomerular function changes with vancomycin","volume":"59","author":"Pais","year":"2022","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e0213221","DOI":"10.1128\/aac.02132-21","article-title":"Glomerular Function and Urinary Biomarker Changes between Vancomycin and Vancomycin plus Piperacillin-Tazobactam in a Translational Rat Model","volume":"66","author":"Chang","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8230","DOI":"10.1158\/1078-0432.CCR-05-1895","article-title":"Liposomal, Nanoparticle, and Conjugated Formulations of Anticancer Agents","volume":"11","author":"Zamboni","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/10717540600814402","article-title":"Pharmacokinetic consequences of pegylation","volume":"13","author":"Hamidi","year":"2006","journal-title":"Drug Deliv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1093\/jac\/dkg024","article-title":"Efficacy of liposome-encapsulated ciprofloxacin compared with ciprofloxacin and ceftriaxone in a rat model of pneumococcal pneumonia","volume":"51","author":"Ellbogen","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100384","DOI":"10.1016\/j.impact.2022.100384","article-title":"PEG-grafted liposomes for enhanced antibacterial and antibiotic activities: An in vivo study","volume":"25","author":"Alavi","year":"2022","journal-title":"NanoImpact"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/jac\/48.3.333","article-title":"Liposome-encapsulated aminoglycosides in pre-clinical and clinical studies","volume":"48","author":"Schiffelers","year":"2001","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Eleraky, N.E., Allam, A., Hassan, S.B., and Omar, M.M. (2020). Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12020142"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ferreira, M., Ogren, M., Dias, J.N.R., Silva, M., Gil, S., Tavares, L., Aires-da-Silva, F., Gaspar, M.M., and Aguiar, S.I. (2021). Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance. Molecules, 26.","DOI":"10.3390\/molecules26072047"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/6\/1582\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:40:49Z","timestamp":1760125249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/6\/1582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,24]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["pharmaceutics15061582"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15061582","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,24]]}}}