A controlled release system of titanocene dichloride by electrospun fiber and its antitumor activity in vitro.

In order to improve both safety and efficacy of cancer chemotherapy of titanocene dichloride and overcome the shortcomings such as instability and short half-life in the human body, we report a controlled release system of titanocene dichloride by electrospun fiber and its in vitro antitumor activity against human lung tumor spca-1 cells. The system was developed by electrospinning. The release profiles of titanocene dichloride in PBS were researched by UV-Vis spectrophotometer. In vitro antitumor activities of the fibers were examined by MTT method. Titanocene dichloride was well incorporated in biodegradable poly(L-lactic acid) fibers. XRD results suggest that titanocene dichloride exists in the amorphous form in the fibers. The controlled release of titanocene dichloride can be gained for long time. MTT showed actual titanocene dichloride content 40, 80, 160 and 240 mg/L from the fibers mat, cell growth inhibition rates of 11.2%, 22.1%, 44.2% and 68.2% were achieved, respectively. The titanocene dichloride released has obvious inhibition effect against lung tumor cells. The system has an effect of controlled release of titanocene dichloride and may be used as an implantable anticancer drug in clinical applications in the future.

[1]  H. Sperling,et al.  Phase II trial of titanocene dichloride in advanced renal-cell carcinoma , 1998, Cancer Chemotherapy and Pharmacology.

[2]  Robert Langer,et al.  Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery. , 2007, Biomaterials.

[3]  E. Monti,et al.  Enhancement of the cytotoxicity of titanocene dichloride by aging in organic co-solvent. , 2005, Journal of inorganic biochemistry.

[4]  N. Kröger,et al.  Phase II Clinical Trial of Titanocene Dichloride in Patients with Metastatic Breast Cancer , 2000, Oncology Research and Treatment.

[5]  P. Supaphol,et al.  Vitamin-loaded electrospun cellulose acetate nanofiber mats as transdermal and dermal therapeutic agents of vitamin A acid and vitamin E. , 2007, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[6]  P. Sadler,et al.  Ti(IV) uptake and release by human serum transferrin and recognition of Ti(IV)-transferrin by cancer cells: understanding the mechanism of action of the anticancer drug titanocene dichloride. , 2000, Biochemistry.

[7]  Kwangsok Kim,et al.  Incorporation and controlled release of a hydrophilic antibiotic using poly(lactide-co-glycolide)-based electrospun nanofibrous scaffolds. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[8]  F. Caruso,et al.  Antitumor titanium compounds. , 2003, Mini reviews in medicinal chemistry.

[9]  K. Zhu,et al.  Preparation, characterization and nasal delivery of alpha-cobrotoxin-loaded poly(lactide-co-glycolide)/polyanhydride microspheres. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[10]  H. Lee,et al.  BCNU-loaded poly(D, L-lactide-co-glycolide) wafer and antitumor activity against XF-498 human CNS tumor cells in vitro. , 2003, International journal of pharmaceutics.

[11]  P. Köpf-Maier,et al.  Tumor inhibition by titanocene complexes: influence on xenografted human adenocarcinomas of the gastrointestinal tract , 2004, Cancer Chemotherapy and Pharmacology.

[12]  Shaobing Zhou,et al.  Release pattern and structural integrity of lysozyme encapsulated in core-sheath structured poly(DL-lactide) ultrafine fibers prepared by emulsion electrospinning. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[13]  Xin Wang,et al.  BCNU-loaded PEG-PLLA ultrafine fibers and their in vitro antitumor activity against Glioma C6 cells. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[14]  N. Bölgen,et al.  Electrospun matrices made of poly(alpha-hydroxy acids) for medical use. , 2007, Nanomedicine.

[15]  Wolfgang J Parak,et al.  Multifunctionalized polymer microcapsules: novel tools for biological and pharmacological applications. , 2007, Small.

[16]  M. Shive,et al.  Surface modification of liposomes for selective cell targeting in cardiovascular drug delivery. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[17]  J. San Román,et al.  Preparation and in vitro release studies of ibuprofen-loaded films and microspheres made from graft copolymers of poly(L-lactic acid) on acrylic backbones. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[18]  Chi-Hwa Wang,et al.  Electrospun Micro- and Nanofibers for Sustained Delivery of Paclitaxel to Treat C6 Glioma in Vitro , 2006, Pharmaceutical Research.

[19]  Y. Mizushima,et al.  Drug-incorporating calcium carbonate nanoparticles for a new delivery system. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[20]  W. Gallagher,et al.  Novel titanocene anti-cancer drugs derived from fulvenes and titanium dichloride , 2004 .

[21]  John Layman,et al.  Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[22]  L. Marks,et al.  Local recurrence after surgery for early stage lung cancer , 2009, Cancer.

[23]  F. Caruso,et al.  Antitumor titanium compounds and related metallocenes. , 2004, Metal ions in biological systems.

[24]  P. Köpf-Maier,et al.  Tumor inhibition by titanocene complexes: Influence upon two xenografted human lung carcinomas , 2004, Journal of Cancer Research and Clinical Oncology.

[25]  M. Harding,et al.  Antitumour metallocenes: structure-activity studies and interactions with biomolecules. , 2000, Current medicinal chemistry.

[26]  P. Sadler,et al.  Metals in Medicine. , 1999, Angewandte Chemie.

[27]  You Han Bae,et al.  Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant MCF-7 tumor. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[28]  Seung Jin Lee,et al.  Porous poly(l-lactide) membranes for guided tissue regeneration and controlled drug delivery: membrane fabrication and characterization , 1997 .

[29]  H. Köpf,et al.  Titanocene dichloride--the first metallocene with cancerostatic activity. , 1979, Angewandte Chemie.

[30]  Jae-Do Nam,et al.  Electrospun dual-porosity structure and biodegradation morphology of Montmorillonite reinforced PLLA nanocomposite scaffolds. , 2005, Biomaterials.

[31]  Moncy V. Jose,et al.  Aligned PLGA/HA nanofibrous nanocomposite scaffolds for bone tissue engineering. , 2009, Acta biomaterialia.

[32]  E. Thiel,et al.  Phase I clinical and pharmacokinetic study of titanocene dichloride in adults with advanced solid tumors. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[33]  Lixin Yang,et al.  Influence of the drug compatibility with polymer solution on the release kinetics of electrospun fiber formulation. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[34]  K. Edwards,et al.  Effects of lipid segregation and lysolipid dissociation on drug release from thermosensitive liposomes. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[35]  A. El-Aneed,et al.  An overview of current delivery systems in cancer gene therapy. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[36]  T. Chung,et al.  A method using biodegradable polylactides/polyethylene glycol for drug release with reduced initial burst. , 1999, International journal of pharmaceutics.

[37]  P. Schwartz,et al.  Phase I trial of intravenous carboplatin and cyclosporin A in refractory gynecologic cancer patients. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[38]  M. Yamashita,et al.  Very long-term outcomes of video-assisted thoracoscopic surgery for lung cancer , 2008, Surgical Endoscopy.