Development of Orally Applicable, Combinatorial Drug-Loaded Nanoparticles for the Treatment of Fibrosarcoma

Autor: Ismail Tuncer Degim, Levent Altintas, Şükran Yılmaz, Gulen Melike Demirbolat
Přispěvatelé: Biruni Üniversitesi, Eczacılık Fakültesi
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
Drug
Drug Compounding
media_common.quotation_subject
education
Administration
Oral
Pharmaceutical Science
Antineoplastic Agents
02 engineering and technology
Polyethylene glycol
Pharmacology
cancer treatment
Chitosan
03 medical and health sciences
chemistry.chemical_compound
Drug Delivery Systems
0302 clinical medicine
Nanocapsules
Oral administration
imatinib mesylate
Nano spray dryer
medicine
Animals
Humans
dexketoprofen trometamol
Tromethamine
Fibrosarcoma
media_common
Mice
Inbred BALB C
combinatorial drug therapy
Anti-Inflammatory Agents
Non-Steroidal
technology
industry
and agriculture
021001 nanoscience & nanotechnology
medicine.disease
Dexketoprofen
3. Good health
Imatinib mesylate
chemistry
Ketoprofen
030220 oncology & carcinogenesis
nanoparticles
fibrosarcoma
Caco-2 Cells
0210 nano-technology
medicine.drug
Popis: This study is financially supported by the Scientific and Technological Research Council of Turkey (TUBITAK, No. 213M675).
Nanoparticulate systems have been receiving a significant attention especially for the treatment of cancer but one of the main hurdles is to produce these developed and high-tech nanosystems in large quantities. Anticancer drug formulations are generally designed for parenteral administrations but oral administration is still the most convenient route. In this study, orally applicable nano-sized chitosan nanoparticles (NPs) were successfully prepared using Nano Spray Dryer. It is possible to produce these NPs in large quantities by simply increasing the processing time using the machine without changing any parameter. A chemotherapeutic agent (imatinib mesylate; IMA) and nonsteroidal anti-inflammatory drug (dexketoprofen trometamol) were loaded together in these NPs. NPs were also functionalized with polyethylene glycol and folic acid to obtain long circulating NPs and tumor targeting. The anti-tumoral activities of formulations showed that these developed NPs can enhance the effectiveness. Animal experiments were performed on fibrosarcoma-bearing mice model, and the treatment with 0.8 mg/mu L/kg IMA-loaded chitosan NPs was found to be successful to slow down the growth of tumors. The tumor tissues were removed from the animals and enzymatic activities were evaluated. The inhibitory effect of tyrosine kinase was found to be enhanced from 36.4% to 68.4% when IMA was used in combination with dexketoprofen trometamol. Furthermore, all dried NPs were found to be stable for more than a year at 25 degrees C. Presented results show that these developed combinatorial drug-loaded NPs can be used for the treatment of fibrosarcoma, and these data can provide an insight, new strategies for productions or alternatives in cancer treatment. (C) 2018 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
Scientific and Technological Research Council of Turkey (TUBITAK) [213M675]
Databáze: OpenAIRE
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