title: Theranostic 3-Dimensional nano brain-implant for prolonged and localized treatment of recurrent glioma.
abstract: Localized and controlled delivery of chemotherapeutics directly in brain-tumor for prolonged periods may radically improve the prognosis of recurrent glioblastoma. Here, we report a unique method of nanofiber by fiber controlled delivery of anti-cancer drug, Temozolomide, in orthotopic brain-tumor for one month using flexible polymeric nano-implant. A library of drug loaded (20 wt%) electrospun nanofiber of PLGA-PLA-PCL blends with distinct in vivo brain-release kinetics (hours to months) were numerically selected and a single nano-implant was formed by co-electrospinning of nano-fiber such that different set of fibres releases the drug for a specific periods from days to months by fiber-by-fiber switching. Orthotopic rat glioma implanted wafers showed constant drug release (116.6 μg/day) with negligible leakage into the peripheral blood (<100 ng) rendering ~1000 fold differential drug dosage in tumor versus peripheral blood. Most importantly, implant with one month release profile resulted in long-term (>4 month) survival of 85.7% animals whereas 07 day releasing implant showed tumor recurrence in 54.6% animals, rendering a median survival of only 74 days. In effect, we show that highly controlled drug delivery is possible for prolonged periods in orthotopic brain-tumor using combinatorial nanofibre libraries of bulk-eroding polymers, thereby controlling glioma recurrence.
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita University, Kochi, 682041, Kerala, India.
authors.forename: Ranjith
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita University, Kochi, 682041, Kerala, India.
authors.forename: Vijayabhaskar Reddy
authors.initials: VR
authors.lastname: Junnuthula
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita University, Kochi, 682041, Kerala, India.
authors.forename: G Siddaramana
authors.initials: GS
authors.lastname: Gowd
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita University, Kochi, 682041, Kerala, India.
authors.forename: Anusha
authors.initials: A
authors.lastname: Ashokan
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita University, Kochi, 682041, Kerala, India.
authors.forename: John
authors.initials: J
authors.lastname: Thomas
authors.affiliation: Central Lab Animal Facility, Amrita Institute of Medical Sciences &Research Centre, Amrita University, Kochi, 682041, Kerala, India.
authors.forename: Reshmi
authors.initials: R
authors.lastname: Peethambaran
authors.affiliation: Department of Neurosurgery, Amrita Institute of Medical Sciences &Research Centre, Amrita University, Kochi, 682041, Kerala, India.
authors.forename: Anoop
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Central Lab Animal Facility, Amrita Institute of Medical Sciences &Research Centre, Amrita University, Kochi, 682041, Kerala, India.
authors.forename: Ayalur Kodakara Kochugovindan
authors.initials: AK
authors.lastname: Unni
authors.affiliation: Department of Neurosurgery, Amrita Institute of Medical Sciences &Research Centre, Amrita University, Kochi, 682041, Kerala, India.
authors.forename: Dilip
authors.initials: D
authors.lastname: Panikar
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita University, Kochi, 682041, Kerala, India.
authors.forename: Shantikumar V
authors.initials: SV
authors.lastname: Nair
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita University, Kochi, 682041, Kerala, India.
authors.forename: Manzoor
authors.initials: M
authors.lastname: Koyakutty
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D002460:Cell Line; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D057139:Nanofibers / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy*; D017208:Rats, Wistar; D016019:Survival Analysis; D000077204:Temozolomide; D000068936:Theranostic Nanomedicine / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D003606:Dacarbazine; D000077204:Temozolomide