{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:01:05Z","timestamp":1787029265610,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Steric stabilization of liposomes using PEGylation has been used widely in pharmaceutical research to overcome the limitations of conventional liposomes and to extend circulation time. PEGylation tended to improve the physicochemical stability and reverse the chemoresistance in multidrug-resistant (MDR) breast cancer cell lines. In this study, PEGylated formulations of disulfiram (DS) and paclitaxel (PAC) were developed using the ethanol-based proliposome technology. Methods: PEGylated liposomal formulations of disulfiram (DS) and paclitaxel (PAC) were developed using the ethanol-based proliposome approach combined with high-pressure homogenization (HPH). The liposomes were characterized for particle size, polydispersity index (PDI), zeta potential, drug loading efficiency (DLE%), and drug entrapment efficiency (DEE%). Cytotoxicity studies were performed on sensitive (MCF7, MDA-MB-231) and chemoresistant (MDA-MB-231PAC10) breast cancer cell lines using the MTT assay to assess the anti-ancer potential of the formulations. Synergistic cytotoxic effects of DS and PAC co-delivery were also evaluated. Results: There was no significant difference in drug loading (DLE%) and drug entrapment efficiency (EE%) between conventional liposomes and the developed PEGylated vesicles. DS demonstrated higher loading in liposomes than PAC, and a greater cytotoxic effect on both sensitive (MCF7 and MDA-MB-231) and chemoresistant (MDA-MB-231PAC10) human breast cancer cell lines. For both DS- and PAC-loaded liposomes, PEGylation did not compromise the cytotoxic effect on both sensitive and chemoresistant cells. Interestingly, the combination of DS- and PAC-loaded PEGylated liposomes had significantly higher cytotoxic effect and lower IC50 than that of each drug alone. Conclusions: Overall, PEGylated liposomal formulation of DS and PAC acted synergistically to reverse the multidrug resistance in breast cancer cells and could serve as a promising system for delivery of PAC and DS simultaneously in one formulation using an alcohol-based proliposome formulation.<\/jats:p>","DOI":"10.3390\/ph18040487","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T06:06:35Z","timestamp":1743141995000},"page":"487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["PEGylated Liposomes of Disulfiram and Paclitaxel: A Promising Chemotherapeutic Combination Against Chemoresistant Breast Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Ammar","family":"Said Suliman","sequence":"first","affiliation":[{"name":"Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahrish","family":"Rehmani","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK"},{"name":"GMPriority Pharma Ltd., Priors Way, Coggeshall, Colchester CO6 1TW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5104-2150","authenticated-orcid":false,"given":"Benjamin","family":"Small","sequence":"additional","affiliation":[{"name":"Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Butcher","sequence":"additional","affiliation":[{"name":"Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7640-471X","authenticated-orcid":false,"given":"Mouhamad","family":"Khoder","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston Upon Thames, London KT1 2EE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinodh","family":"Kannappan","sequence":"additional","affiliation":[{"name":"Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0509-2605","authenticated-orcid":false,"given":"Weiguang","family":"Wang","sequence":"additional","affiliation":[{"name":"Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelbary","family":"Elhissi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7670-2859","authenticated-orcid":false,"given":"Mohammad","family":"Najlah","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1027","DOI":"10.1016\/S2214-109X(20)30215-1","article-title":"Global burden and trends in premenopausal and postmenopausal breast cancer: A population-based study","volume":"8","author":"Heer","year":"2020","journal-title":"Lancet Glob. 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