TY - JOUR ID - 19834 TI - Preparation, characterization, and biodistribution of glutathione PEGylated nanoliposomal doxorubicin for brain drug delivery with a post-insertion approach JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Mehrabian, Amin AU - Vakili-Ghartavol, Roghayyeh AU - Mashreghi, Mohammad AU - Shokooh Saremi, Sara AU - Badiee, Ali AU - Arabi, Leila AU - Alavizadeh, Hoda AU - Moosavian, Seyedeh Alia AU - Jaafari, Mahmoud Reza AD - Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran AD - Department of Medical Nanotechnology, Shiraz University of Medical Sciences, Shiraz, Iran Y1 - 2022 PY - 2022 VL - 25 IS - 3 SP - 302 EP - 312 KW - Biodistribution KW - Blood-brain barrier KW - Brain drug delivery KW - Glutathione KW - Liposome KW - Post-insertion DO - 10.22038/ijbms.2022.60306.13369 N2 - Objective(s): Brain cancer treatments have mainly failed due to their inability to cross the blood-brain barrier. Several studies have confirmed the presence of glutathione (GSH) receptors on BBB’s surface, as a result, products like 2B3-101, which contain over 5% pre-inserted GSH PEGylated liposomal Doxorubicin, are being tested in clinical trials. Here we conducted the PEGylated nanoliposomal Doxorubicin particles that are covalently attached to the glutathione using the post-insertion technique. Compared with the pre-insertion approach, the post-insertion method is notably simpler, faster, and more cost-effective, making it ideal for large-scale pharmaceutical manufacturing. Materials and Methods: The ligands of the DSPE PEG(2000) Maleimide-GSH were introduced in the amounts of 25, 50, 100, 200, and 400 on the available Caelyx. Following physicochemical evaluations, animal experiments such as biodistribution, fluorescence microscopy, and pharmacokinetics were done. Results: In comparison with Caelyx, the 200L and 400L treatment arms were the most promising formulations. We showed that nanocarriers containing 40 times fewer GSH micelles than 2B3-101 significantly increased blood-brain barrier penetrance. Due to the expressed GSH receptors on tissues as an endogenous antioxidant, Doxorubicin will likely concentrate in the liver, spleen, heart, and lung in comparison with Caelyx, according to other tissue analyses. Conclusion: The post-insertion technique was found a successful approach with more pharmaceutical aspects for large-scale production. Moreover, further investigations are highly recommended to determine the efficacy of 5% post-inserted GSH targeted nanoliposomes versus 2B3-101 as a similar formulation with a different preparation method. UR - https://ijbms.mums.ac.ir/article_19834.html L1 - https://ijbms.mums.ac.ir/article_19834_2afd305e0a65e4ff3f966a2f0d41146c.pdf ER -