title: In vivo pharmacological evaluation and efficacy study of methotrexate-encapsulated polymer-coated layered double hydroxide nanoparticles for possible application in the treatment of osteosarcoma.
abstract: Considering the existing drawbacks of methotrexate (MTX) with respect to its solubility and toxicity, we incorporated it in a nanoceramic matrix, Mg-Al-layered double hydroxide (LDH) to form LDH-MTX nanoparticles, and the same was in turn encapsulated in a nontoxic and biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), to arrest the initial burst release and dose-dumping-related toxicity, already reported by our group. Our present study was designed to evaluate the pharmacokinetics, tissue distribution, survival rate of the test animals, and antitumor efficacy of the PLGA-LDH-MTX nanoparticles and its counterpart without LDH, PLGA-MTX nanoparticles compared with bare MTX. The median lethal dose (LD50) of the former was higher, compared with bare MTX, using Balb/c nude mice, indicating it to be completely safe for use. Also, a comparative pharmacokinetic and antitumour efficacy study using MTX, PLGA-MTX, and PLGA-LDH-MTX nanoparticles in osteosarcoma-induced Balb/c nude mice in vivo demonstrated superiority of PLGA-LDH-MTX as compared to PLGA-MTX and bare MTX. The results suggest that PLGA-LDH-MTX nanoparticles might exhibit potential advantages over the present-day chemotherapy over bare MTX, for the possibility of treatment of osteosarcoma.
authors.affiliation: CSIR-Central Glass and Ceramic Research Institute, 196, Raja S.C. Mullick Road, Jadavpur, Kolkata, 700 032, India.
authors.forename: Sayantan
authors.initials: S
authors.lastname: Ray
authors.affiliation: CSIR-Central Glass and Ceramic Research Institute, 196, Raja S.C. Mullick Road, Jadavpur, Kolkata, 700 032, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Saha
authors.affiliation: Jadavpur University, Jadavpur, Kolkata, 700 032, India.
authors.forename: Biswanath
authors.initials: B
authors.lastname: Sa
authors.affiliation: CSIR-Central Glass and Ceramic Research Institute, 196, Raja S.C. Mullick Road, Jadavpur, Kolkata, 700 032, India. jui@cgcri.res.in.
authors.forename: Jui
authors.initials: J
authors.lastname: Chakraborty
mesh_terms: D000535:Aluminum / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D006878:Hydroxides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D006878:Hydroxides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000535:Aluminum; D008274:Magnesium; D008727:Methotrexate
keywords: Antitumor efficacy; Hepatotoxicity and nephrotoxicity; Methotrexate; Mg–Al-layered double hydroxide; Pharmacokinetics; Poly(D,L-lactide-co-glycolide); Survival rate; Tissue distribution