title: Development and evaluation of transferrin-stabilized paclitaxel nanocrystal formulation.
abstract: The aim of the present study was to prepare and evaluate a paclitaxel nanocrystal-based formulation stabilized by serum protein transferrin in a non-covalent manner. The pure paclitaxel nanocrystals were first prepared using an antisolvent precipitation method augmented by sonication. The serum protein transferrin was selected for use after evaluating the stabilizing effect of several serum proteins including albumin and immunoglobulin G. The formulation contained approximately 55-60% drug and was stable for at least 3months at 4°C. In vivo antitumor efficacy studies using mice inoculated with KB cells demonstrate significantly higher tumor inhibition rate of 45.1% for paclitaxel-transferrin formulation compared to 28.8% for paclitaxel nanosuspension treatment alone. Interestingly, the Taxol(®) formulation showed higher antitumor activity than the paclitaxel-transferrin formulation, achieving a 93.3% tumor inhibition rate 12days post initial dosing. However, the paclitaxel-transferrin formulation showed a lower level of toxicity, which is indicated by a steady increase in body weight of mice over the treatment period. In comparison, treatment with Taxol(®) resulted in toxicity issues as body weight decreased. These results suggest the potential benefit of using a serum protein in a non-covalent manner in conjunction with paclitaxel nanocrystals as a promising drug delivery model for anticancer therapy.
authors.affiliation: Purdue University, Department of Industrial and Physical Pharmacy, West Lafayette 47907, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Purdue University, Department of Industrial and Physical Pharmacy, West Lafayette 47907, USA.
authors.forename: Zhao-hui
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Purdue University, Department of Industrial and Physical Pharmacy, West Lafayette 47907, USA.
authors.forename: Tonglei
authors.initials: T
authors.lastname: Li
authors.affiliation: Purdue University, Electrical and Computer Engineering Technology, West Lafayette 47907, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: McNally
authors.affiliation: Purdue University, Department of Industrial and Physical Pharmacy, West Lafayette 47907, USA; Purdue University, Weldon School of Biomedical Engineering, West Lafayette 47907, USA. Electronic address: kpark@purdue.edu.
authors.forename: Kinam
authors.initials: K
authors.lastname: Park
authors.affiliation: Indiana University School of Medicine, Department of Cellular & Integrative Physiology, Indianapolis 46202, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Sturek
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004355:Drug Stability; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010316:Particle Size; D012709:Serum Albumin / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry*; D014168:Transferrin / Q000008:administration & dosage / Q000737:chemistry*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D012709:Serum Albumin; D043823:Taxoids; D014168:Transferrin; C115455:paclitaxel-transferrin
keywords: Albumin; Antitumor efficacy; Nanocrystal; Paclitaxel; Taxol; Transferrin