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

Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved..

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 antitumoral 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/μL/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°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.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:107

Enthalten in:

Journal of pharmaceutical sciences - 107(2018), 5 vom: 20. Mai, Seite 1398-1407

Sprache:

Englisch

Beteiligte Personen:

Demirbolat, Gulen Melike [VerfasserIn]
Altintas, Levent [VerfasserIn]
Yilmaz, Sukran [VerfasserIn]
Degim, Ismail Tuncer [VerfasserIn]

Links:

Volltext

Themen:

023C2WHX2V
8A1O1M485B
9012-76-4
90Y4QC304K
Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Cancer treatment
Chitosan
Combinatorial drug therapy
Dexketoprofen trometamol
Fibrosarcoma
Imatinib Mesylate
Imatinib mesylate
Journal Article
Ketoprofen
N674F7L21E
Nanocapsules
Nanoparticles
Research Support, Non-U.S. Gov't
Tromethamine

Anmerkungen:

Date Completed 08.04.2019

Date Revised 08.04.2019

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.xphs.2018.01.006

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM280012462