Design and optimization of novel paclitaxel-loaded folate-conjugated amphiphilic cyclodextrin nanoparticles.
As nanomedicines are gaining momentum in the therapy of cancer, new biomaterials emerge as alternative platforms for the delivery of anticancer drugs with bioavailability problems. In this study, two novel amphiphilic cyclodextrins (FCD-1 and FCD-2) conjugated with folate group to enable active targeting to folate positive breast tumors were introduced. The objective of this study was to develop and characterize new folated-CD nanoparticles via 3(2) factorial design for optimal final parameters. Full physicochemical characterization studies were performed. Blank and paclitaxel loaded FCD-1 and FCD-2 nanoparticles remained within the range of 70-275nm and 125-185nm, respectively. Zeta potential values were neutral and -20mV for FCD-1 and FCD-2 nanoparticles, respectively. Drug release studies showed initial burst release followed by a longer sustained release. Blank nanoparticles had no cytotoxicity against L929 cells. T-47D and ZR-75-1 human breast cancer cells with different levels of folate receptor expression were used to assess anti-cancer efficacy. Through targeting the folate receptor, these nanoparticles were efficiently engulfed by the breast cancer cells. Additionally, breast cancer cells became more sensitive to cytotoxic and/or cytostatic effects of PCX delivered by FCD-1 and FCD-2. In conclusion, these novel folate-conjugated cyclodextrin nanoparticles can therefore be considered as promising alternative systems for safe and effective delivery of paclitaxel with a folate-dependent mechanism.
Hacettepe University Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100 Sıhhiye-Ankara, Turkey.
Nazlı
N
Erdoğar
Hacettepe University, Cancer Institute, Department of Basic Oncology, 06100 Sıhhiye-Ankara, Turkey.
Güneş
G
Esendağlı
University of Aalborg, Faculty of Engineering and Science, Department of Biotechnology, Chemistry and Environmental Engineering, 9000 Aalborg, Denmark.
Thorbjorn T
TT
Nielsen
Hacettepe University, Faculty of Science, Department of Chemistry, 06800 Beytepe-Ankara, Turkey.
Murat
M
Şen
Hacettepe University Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100 Sıhhiye-Ankara, Turkey.
Levent
L
Öner
Hacettepe University Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100 Sıhhiye-Ankara, Turkey. Electronic address: eremino@hacettepe.edu.tr.
Erem
E
Bilensoy
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D003505:Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D051379:Mice; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry*; D010316:Particle Size
D000970:Antineoplastic Agents; D003505:Cyclodextrins; D004337:Drug Carriers; D005492:Folic Acid; D017239:Paclitaxel
Active targeting; Amphiphilic cyclodextrin; Cancer; Factorial design; Nanoparticle; Paclitaxel