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The presence of glutathione (GSH) receptors on the BBB surface has been demonstrated in numerous papers; consequently, products containing glutathione as a targeting ligand coupled with nanoliposomes are used to enhance drug delivery across the BBB. Here, the 5% pre\u2010inserted PEG2000\u2010GSH PEGylated liposomal doxorubicin was conducted according to 2B3\u2010101 being tested in clinical trials. In addition, PEGylated nanoliposomal doxorubicin connected to the spacer\u2010GSH targeting ligand (GSGGCE) and the PEG3400 was conducted using post\u2010insertion method. Next, in vivo biodistribution of the produced formulations was tested on healthy mice to see if GSGGCE, as the targeted ligand, could cross the BBB compared to 5% pre\u2010inserted PEG2000\u2010GSH and Caelyx\n                    <jats:sup>\u00ae<\/jats:sup>\n                    . Compared to the pre\u2010inserted formulation and Caelyx\n                    <jats:sup>\u00ae<\/jats:sup>\n                    , the post\u2010inserted formulations' concentration was lower in the heart and higher in brain tissues, resulting in boosting the brain concentration of accumulated doxorubicin with fewer possible side effects, including cardiotoxicity. In comparison to the pre\u2010insertion procedure, the post\u2010insertion method is easier, faster, and more cost\u2010effective. Moreover, employing PEG3400 and the post\u2010insertion approach in the PEG3400\u2010GSGGCE liposomal formulations was found to be effective in crossing the\u00a0BBB.\n                  <\/jats:p>","DOI":"10.1049\/nbt2.12111","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T07:53:46Z","timestamp":1672732426000},"page":"112-124","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The comparison of biodistribution of glutathione PEGylated nanoliposomal doxorubicin formulations prepared by pre\u2010insertion and post\u2010insertion methods for brain delivery in normal mice"],"prefix":"10.1049","volume":"17","author":[{"given":"Amin","family":"Mehrabian","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Nanotechnology School of Pharmacy Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Nanotechnology Research Center Pharmaceutical Technology 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