title: Surface engineered polymeric nanocarriers mediate the delivery of transferrin-methotrexate conjugates for an improved understanding of brain cancer.
abstract: The objective of present study was to enhance permeation of bioactive molecules across blood brain barrier (BBB) through polysorbate 80 coated poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with methotrexate-transferrin (Tw-Mtx-Tf-NP) conjugates (Mtx-Tf). The easy trans-BBB migration of developed formulations through endocytosis, and inhibition of P-gp efflux pump present in brain were established by Pluronic F-68 and/or polysorbate 80 (Tween 80/Tw). The over-expression of transferrin (Tf) receptors on cancer cell surface allowed targeted and sustained delivery of Mtx-Tf conjugated to brain cancer cells by receptor mediated endocytosis. The developed formulations showed improved penetration in comparison to non-targeting experimental NP controls. The transportation potential and bio-distribution studies of such nanosized polymeric carriers showing successful migration and trans-BBB passage was carried out by administering FITC labeled drug loaded NPs to albino rats through intravenous route. We have validated anti-tumor efficiency of newly formulated and drug loaded NPs compared to controls in experimentally induced tumor-harboring rat model. The present study suggests greater compatibility, less organ toxicity and higher anti-tumor activity of developed formulations due to their targeting and sustained delivery potential in cancer therapeutic interventions. In conclusion, our findings of targeted and sustained drug delivery potential of NPs for are corroborated with in vitro and in vivo evidence, and formulated novel delivery vehicle shows its value in developing new tools for treating brain cancer.
authors.affiliation: Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, M.P. 470003, India; Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India; UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh 160014, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, M.P. 470003, India; Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India.
authors.forename: Ashay
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, M.P. 470003, India; Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India.
authors.forename: Neeraj K
authors.initials: NK
authors.lastname: Garg
authors.affiliation: Department of Periodontics, College of Dental Medicine Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Tyagi
authors.affiliation: Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India; UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh 160014, India.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
authors.affiliation: Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India.
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Katare
authors.affiliation: Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; The Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: th.webster@neu.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Webster
authors.affiliation: Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, M.P. 470003, India. Electronic address: vandansonidops@gmail.com.
authors.forename: Vandana
authors.initials: V
authors.lastname: Soni
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D008727:Methotrexate / Q000737:chemistry / Q000494:pharmacology; D053769:Nanocapsules / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D014168:Transferrin / Q000737:chemistry / Q000494:pharmacology
chemical_list: D053769:Nanocapsules; D014168:Transferrin; D008727:Methotrexate
keywords: Brain cancer; Brain targeting; Methotrexate; Nanoparticles; PLGA; Polysorbate 80; Transferrin