title: Preclinical Toxicity of Paclitaxel Biopolymer Formulation.
abstract: Poly(hydroxyalkanoates) (PHA) have recently attracted increasing attention due to their biodegradability and high biocompatibility, which makes them suitable for the development of new prolong drug formulations.
  
  
  
  A preclinical toxicology study of paclitaxel biopolymer formulation (PBF) (paclitaxel-loaded poly(3- hydroxybutyrate) (PHB) microparticles) was done in order to assess its safety and to forecast side and toxic effects in a clinical study on patients.
  
  
  
  PHB microparticles loaded with antitumor cytostatic drug PTX were obtained by spray-drying method using Nano Spray Dryer B-90. The comprehensive study of cytotoxicity (on bone marrow stem cells), acute and chronic toxicity, allergenic and pyrogenic properties, histological investigation (in mice, rats and rabbits) of obtained PBF was carried out.
  
  
  
  The acute toxicity study showed that PBF is much less toxic in equivalent PTX-content doses than PTX in conventional formulation when administered intraperitoneally to mice and rats. However, the chronic toxicity study showed that at intraperitoneal administration PBF has distinct cumulative properties and toxic effects that prevent PBF from clinical testing in current composition.
  
  
  
  Thus, the PBF as a prolong drug needs to correct its parameters for further drug formulation development.
authors.affiliation: FGBU N.N. Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation, Moscow. Russian Federation.
authors.forename: Nadezhda P
authors.initials: NP
authors.lastname: Ermakova
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow. Russian Federation.
authors.forename: Anton P
authors.initials: AP
authors.lastname: Bonartsev
authors.affiliation: A.N. Bach Institute of Biochemistry, The Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences, Moscow. Russian Federation.
authors.forename: Anton L
authors.initials: AL
authors.lastname: Zernov
authors.affiliation: FGBU N.N. Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation, Moscow. Russian Federation.
authors.forename: Olga I
authors.initials: OI
authors.lastname: Konyaeva
authors.affiliation: FGBU N.N. Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation, Moscow. Russian Federation.
authors.forename: Natalia Y
authors.initials: NY
authors.lastname: Kulbachevskaya
authors.affiliation: FGBU N.N. Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation, Moscow. Russian Federation.
authors.forename: Irina B
authors.initials: IB
authors.lastname: Merkulova
authors.affiliation: FGBU N.N. Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation, Moscow. Russian Federation.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Abramovac
authors.affiliation: FGBU N.N. Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation, Moscow. Russian Federation.
authors.forename: Vera A
authors.initials: VA
authors.lastname: Chaley
authors.affiliation: Department of Bioengineering, Faculty of Biology, Moscow State University, P.O. Box: 119991, Moscow. Russian Federation.
authors.forename: Irina I
authors.initials: II
authors.lastname: Zharkova
authors.affiliation: A.N. Bach Institute of Biochemistry, The Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences, Moscow. Russian Federation.
authors.forename: Sergey G
authors.initials: SG
authors.lastname: Yakovlev
authors.affiliation: A.N. Bach Institute of Biochemistry, The Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences, Moscow. Russian Federation.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Myshkina
authors.affiliation: A.N. Bach Institute of Biochemistry, The Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences, Moscow. Russian Federation.
authors.forename: Tatiana K
authors.initials: TK
authors.lastname: Mahina
authors.affiliation: A.N. Bach Institute of Biochemistry, The Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences, Moscow. Russian Federation.
authors.forename: Garina A
authors.initials: GA
authors.lastname: Bonartseva
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow. Russian Federation.
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Shaitan
authors.affiliation: FGBU N.N. Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation, Moscow. Russian Federation.
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Bukhman
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D001704:Biopolymers / Q000737:chemistry*; D004304:Dosage Forms; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D008297:Male; D051379:Mice; D008863:Microspheres; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000091402:Prohibitins; D011817:Rabbits; D051381:Rats; D014018:Tissue Distribution; D023382:Toxicity Tests, Acute; D059550:Toxicity Tests, Subchronic
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001704:Biopolymers; D004304:Dosage Forms; D004337:Drug Carriers; C000717332:Phb protein, rat; D000091402:Prohibitins; D017239:Paclitaxel
keywords: Anticancer agent; adaptive therapy; allergenicity; paclitaxel; poly(3-hydroxybutyrate); pyrogenicity; toxicity