Preparation, characterization, and biodistribution of glutathione PEGylated nanoliposomal doxorubicin for brain drug delivery with a post-insertion approach

Publish Year: 1401
نوع سند: مقاله ژورنالی
زبان: English
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JR_IJBMS-25-3_005

تاریخ نمایه سازی: 15 فروردین 1401

Abstract:

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 ۲B۳-۱۰۱, which contain over ۵% 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(۲۰۰۰) Maleimide-GSH were introduced in the amounts of ۲۵, ۵۰, ۱۰۰, ۲۰۰, and ۴۰۰ on the available Caelyx. Following physicochemical evaluations, animal experiments such as biodistribution, fluorescence microscopy, and pharmacokinetics were done. Results: In comparison with Caelyx, the ۲۰۰L and ۴۰۰L treatment arms were the most promising formulations. We showed that nanocarriers containing ۴۰ times fewer GSH micelles than ۲B۳-۱۰۱ 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 ۵% post-inserted GSH targeted nanoliposomes versus ۲B۳-۱۰۱ as a similar formulation with a different preparation method.

Authors

Amin Mehrabian

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Roghayyeh Vakili-Ghartavol

Department of Medical Nanotechnology, Shiraz University of Medical Sciences, Shiraz, Iran

Mohammad Mashreghi

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Sara Shokooh Saremi

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Ali Badiee

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Leila Arabi

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Hoda Alavizadeh

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Seyedeh Alia Moosavian

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Mahmoud Reza Jaafari

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

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