title: New Poly(3-hydroxybutyrate) Microparticles with Paclitaxel Sustained Release for Intraperitoneal Administration.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  This study was conducted to develop new prolong paclitaxel (PTX) formulation based on poly(3- hydroxybutyrate) (PHB) microparticles.
  
  
  METHODS
  PHB microparticles loaded with antitumor cytostatic drug PTX were obtained by spray-drying method using Nano Spray Dryer B-90. The PTX release kinetics in vitro from PHB microparticles and their cytotoxity on murine hepatoma cell line MH-22a were studied. Microparticles antitumor activity in vivo was studied using intraperitoneally (i.p.) transplanted tumor models: murine Lewis lung carcinoma and xenografts of human breast cancer RMG1.
  
  
  RESULTS
  Uniform PTX release from PHB-microparticles during 2 months was observed. PTX-loaded PHB microparticles have demonstrated a significant antitumor activity versus pure drug both in vitro in murine hepatoma cells and in vivo when administered i.p. to mice with murine Lewis lung carcinoma and xenografts of human breast cancer RMG1.
  
  
  CONCLUSIONS
  The developed technique of PTX sustained delivery from PHB-microparticles has therapeutic potential as prolong anticancer drug formulation.
authors.affiliation: Faculty of Biology, Moscow State University, Leninskie gory, 1-12, Moscow 119991, Russian Federation.
authors.forename: Anton P
authors.initials: AP
authors.lastname: Bonartsev
authors.affiliation: A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Anton L
authors.initials: AL
authors.lastname: Zernov
authors.affiliation: A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Sergey G
authors.initials: SG
authors.lastname: Yakovlev
authors.affiliation: Faculty of Biology, Moscow State University, Moscow, Russian Federation.
authors.forename: Irina I
authors.initials: II
authors.lastname: Zharkova
authors.affiliation: A.N. Bach Institute of Biochemistry, Research Center 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, Research Center 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, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Garina A
authors.initials: GA
authors.lastname: Bonartseva
authors.affiliation: Federal State Budgetary Institution «N.N. Blokhin Russian Cancer Research Center», Moscow, Russian Federation.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Andronova
authors.affiliation: Federal State Budgetary Institution «N.N. Blokhin Russian Cancer Research Center», Moscow, Russian Federation.
authors.forename: Galina B
authors.initials: GB
authors.lastname: Smirnova
authors.affiliation: Federal State Budgetary Institution «N.N. Blokhin Russian Cancer Research Center», Moscow, Russian Federation.
authors.forename: Juliya A
authors.initials: JA
authors.lastname: Borisova
authors.affiliation: Federal State Budgetary Institution «N.N. Blokhin Russian Cancer Research Center», Moscow, Russian Federation.
authors.forename: Mikhail S
authors.initials: MS
authors.lastname: Kalishjan
authors.affiliation: Faculty of Biology, Moscow State University, Moscow, Russian Federation.
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Shaitan
authors.affiliation: Federal State Budgetary Institution «N.N. Blokhin Russian Cancer Research Center», Moscow, Russian Federation.
authors.forename: Helena M
authors.initials: HM
authors.lastname: Treshalina
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006885:Hydroxybutyrates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D015394:Molecular Structure; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000091402:Prohibitins; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014407:Tumor Cells, Cultured; D000094122:Polyhydroxybutyrates
chemical_list: D000970:Antineoplastic Agents; D006885:Hydroxybutyrates; D017239:Paclitaxel; D011091:Polyesters; D000091402:Prohibitins; C000717328:PHB protein, human; C003182:poly-beta-hydroxybutyrate; D000094122:Polyhydroxybutyrates
keywords: Paclitaxel; adaptive therapy; antitumor activity; microparticles; poly(3-hydroxybutyrate); spray-drying; sustained release