title: Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route.
abstract: Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors.
authors.affiliation: C.U. Shah College of Pharmacy, S.N.D.T Women's University, Juhu Tara Road, Santacruz (West), Mumbai 400 049, India. Electronic address: darshanaj_cup@yahoo.com.
authors.forename: Darshana S
authors.initials: DS
authors.lastname: Jain
authors.affiliation: C.U. Shah College of Pharmacy, S.N.D.T Women's University, Juhu Tara Road, Santacruz (West), Mumbai 400 049, India.
authors.forename: Amrita N
authors.initials: AN
authors.lastname: Bajaj
authors.affiliation: C.U. Shah College of Pharmacy, S.N.D.T Women's University, Juhu Tara Road, Santacruz (West), Mumbai 400 049, India. Electronic address: rajani.athawale@gmail.com.
authors.forename: Rajani B
authors.initials: RB
authors.lastname: Athawale
authors.affiliation: C.U. Shah College of Pharmacy, S.N.D.T Women's University, Juhu Tara Road, Santacruz (West), Mumbai 400 049, India.
authors.forename: Shruti S
authors.initials: SS
authors.lastname: Shikhande
authors.affiliation: H. R Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Gude Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410 210, India.
authors.forename: Peeyush N
authors.initials: PN
authors.lastname: Goel
authors.affiliation: Gude Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410 210, India.
authors.forename: Rajiv P
authors.initials: RP
authors.lastname: Gude
authors.affiliation: Cipla Pvt. Ltd., Vikhroli (West), Mumbai, India.
authors.forename: Satish
authors.initials: S
authors.lastname: Patil
authors.affiliation: Cipla Pvt. Ltd., Vikhroli (West), Mumbai, India.
authors.forename: Preeti
authors.initials: P
authors.lastname: Raut
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006207:Half-Life; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D009297:Nasal Mucosa / Q000187:drug effects; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; D020442:Poloxamer; C033616:poly(lactide); D008727:Methotrexate
keywords: Brain tumors; Intranasal; Mucociliary clearance; Poly lactic acid (PLA); Thermosensitive