title: Investigation of imatinib loaded surface decorated biodegradable nanocarriers against glioblastoma cell lines: Intracellular uptake and cytotoxicity studies.
abstract: Overexpression of P-glycoprotein (P-gp) efflux transporter in glioma cells thwarts the build-up of therapeutic concentration of drugs usually resulting into poor therapeutic outcome. To surmount aforesaid challenge, Imatinib (IMM) loaded Poly-lactide-co-glycolic acid nanoparticles (IMM-PLGA-NPs) were developed and optimized by Box Behnken Design as a new treatment stratagem in malignant glioma. Optimized NPs were functionalized with Pluronic(®) P84, P-gp inhibitor (IMM-PLGA-P84-NPs) which showed size, PDI, zeta potential, drug loading, 182.63±13.56nm, 0.196±0.021, -15.2±1.49mV, 40.63±2.04μg/mg, respectively. Intracellular uptake study conducted on A172, U251MG and C6 glioma cells demonstrated significantly high uptake of IMM through NPs when compared with IMM solution (IMM-S), p<0.001. IMM-PLGA-P84-NPs showed better uptake in P-gp expressing cell line (U251MG and C6) while uncoated NPs showed higher uptake in non-P-gp expressing cell line (A-172). Cytotoxicity studies demonstrated significantly low IC50 for both IMM-PLGA-NPs and IMM-PLGA-P84-NPs when compared with IC50 of IMM-S. IMM-PLGA-P84-NPs showed a significantly low IC50 against P-gp overexpressing cell lines when compared with IC50 of IMM-PLGA-NPs. In contrary, IMM-PLGA-NPs showed lower IC50 against non P-gp expressing cell line. This study demonstrated the feasibility of targeting surface decorated NPs to multidrug resistant gliomas. However, to address its clinical utility extensive in vivo studies are required.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors.forename: Abrar M
authors.initials: AM
authors.lastname: Khan
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors.forename: Farhan Jalees
authors.initials: FJ
authors.lastname: Ahmad
authors.affiliation: Product Development Cell, National Institute of Immunology, New Delhi, India.
authors.forename: Amulya K
authors.initials: AK
authors.lastname: Panda
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India. Electronic address: stalegaonkar@gmail.com.
authors.forename: Sushama
authors.initials: S
authors.lastname: Talegaonkar
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry*; D065546:Drug Liberation; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D004337:Drug Carriers; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000068877:Imatinib Mesylate
keywords: 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (PubChem CID: 2723939); 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (PubChem CID: 64965); Acetonitrile (PubChem CID: 6342); DMSO (PubChem CID: 679); Dichloromethane (PubChem CID: 6251); Glioblastoma; Imatinib mesylate; Imatinib mesylate (PubChem CID: 5291); Mannitol (PubChem CID: 6251); P-glycoprotein; PLGA; Pluronic (PubChem CID:24751); Pluronic(®) P84; Poly(DL-lactic-co-glycolic acid) (PubChem CID: 23111554); Polyvinyl alcohol (Pubchem CID: 11199)