Brain targeted delivery of rapamycin using transferrin decorated nanostructured lipid carriers

Brain targeted delivery of rapamycin using transferrin decorated nanostructured lipid carriers Fatemeh Khonsari Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran http://orcid.org/0000-0002-4651-5988 Mostafa Heydari Department of Pharmaceutical Nanotechnology, Faculty of pharmacy, Tehran University of Medical Sciences, Tehran, Iran http://orcid.org/0000-0002-4119-0328 Rassoul Dinarvand Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran http://orcid.org/0000-0003-0694-7556 Mohammad Sharifzadeh Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran Iran http://orcid.org/0000-0003-2991-7384 Fatemeh Atyabi Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Department of Pharmaceutical Nanotechnology, Faculty of pharmacy, Tehran University of Medical Sciences, Tehran, Iran Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran http://orcid.org/0000-0002-9421-8750

Introduction: Recent studies showed that rapamycin, as a mammalian target of rapamycin (mTOR) inhibitor, could have beneficial therapeutic effects for the central nervous system (CNS) related diseases. However, the immunosuppressive effect of rapamycin as an adverse effect, the low water solubility, and the rapid in vivo degradation along with the blood-brain barrier-related challenges restricted the clinical use of this drug for brain diseases. To overcome these drawbacks, a transferrin (Tf) decorated nanostructured lipid carrier (NLC) containing rapamycin was designed and developed. Methods: Rapamycin-loaded cationic and bare NLCs were prepared using solvent diffusion and sonication method and well characterized. The optimum cationic NLCs were physically decorated with Tf. For in vitro study, the MTT assay and intracellular uptake of nanoparticles on U-87 MG glioblastoma cells were assessed. The animal biodistribution of nanoparticles was evaluated by fluorescent optical imaging. Finally, the in vivo effect of NLCs on the immune system was also studied. Results: Spherical NLCs with small particle sizes ranging from 120 to 150 nm and high entrapment efficiency of more than 90%, showed ≥80% cell viability. More importantly, Tf-decorated NLCs in comparison with bare NLCs, showed a significantly higher cellular uptake (97% vs 60%) after 2 hours incubation and further an appropriate brain accumulation with lower uptake in untargeted tissue in mice. Surprisingly, rapamycin-loaded NLCs exhibited no immunosuppressive effect. Conclusion: Our findings proposed that the designed Tf-decorated NLCs could be considered as a safe and efficient carrier for targeted brain delivery of rapamycin which may have an important value in the clinic for the treatment of neurological disorders.
10 09 2021 10 09 2021 1 10.34172/crossmark_policy bi.tbzmed.ac.ir false Tabriz University of Medical Sciences Tabriz University of Medical Sciences 2020-08-28 2021-04-18 2021-10-09 10.34172/bi.2021.23389 20211201132554 https://bi.tbzmed.ac.ir/Inpress/bi-23389 https://bi.tbzmed.ac.ir/Inpress/bi-23389.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23389.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23389.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23389.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23389.pdf