PHBV/PLGA nanoparticles for enhanced delivery of 5-fluorouracil as promising treatment of colon cancer

被引:28
作者
Handali, Somayeh [1 ]
Moghimipour, Eskandar [2 ,3 ]
Rezaei, Mohsen [4 ]
Ramezani, Zahra [2 ]
Dorkoosh, Farid Abedin [1 ,5 ]
机构
[1] Univ Tehran Med Sci, MBRC, Tehran, Iran
[2] Ahvaz Jundishapur Univ Med Sci, Nanotechnol Res Ctr, Ahvaz, Iran
[3] Ahvaz Jundishapur Univ Med Sci, Cellular & Mol Res Ctr, Ahvaz, Iran
[4] Tarbiat Modares Univ, Fac Med Sci, Dept Toxicol, Tehran, Iran
[5] Univ Tehran Med Sci, Fac Pharm, Dept Pharmaceut, Tehran, Iran
关键词
5-Fluorouracil; poly (3-hydroxybutyrate-co-3-hydroxyvalerate acid); poly (lactic-co-glycolic acid); nanoparticles; cancer; LOADED PLGA NANOPARTICLES; IN-VITRO; POLYMERIC NANOPARTICLES; OPTIMIZATION; ENCAPSULATION; FORMULATION; LIPOSOMES; DESIGN; DRUG; CYTOTOXICITY;
D O I
10.1080/10837450.2019.1684945
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
5-Fluorouracil (5-FU) is one of the most widely used agents in the first-line chemotherapy for colon cancer. However, clinical use of 5-FU is limited because of the low efficacy of drug uptake and systemic toxic effects. Therefore, there is a critical need to find better drug delivery systems in order to improve the efficacy of the drug. In the present study, we have developed a novel combination drug delivery system based on PHBV/PLGA NPs for delivery of 5-FU to cancer cells. NPs were prepared by the double emulsion method and their optimization of preparation was evaluated using Box-Behnken design (BBD) of response surface methodology (RSM). 5-FU loaded NPs were characterized by scanning electron microscope (SEM), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), and Fourier transformed infra-red spectroscopy (FT-IR). SEM image implied that NPs were spherical in shape and the results of DSC, TGA, and FT-IR suggest that 5-FU was encapsulated into NPs. The obtained results revealed that 5-FU loaded PHBV/PLGA NPs induced significant higher cell death at concentration much lower than free 5-FU. Results of hemolysis assay indicated that the NPs were hemo-compatible. In vivo anti-tumor studies showed that 5-FU loaded NPs reduced tumor volume significantly in comparison with free 5-FU. As the first example of using PHBV/PLGA as nano-drug delivery system with enhanced anti-tumor activities, this study establishes PHBV/PLGA as a novel promising drug delivery platform for treatment of colon cancer.
引用
收藏
页码:206 / 218
页数:13
相关论文
共 51 条
[1]   PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect [J].
Acharya, Sarbari ;
Sahoo, Sanjeeb K. .
ADVANCED DRUG DELIVERY REVIEWS, 2011, 63 (03) :170-183
[2]   Development of hematin conjugated PLGA nanoparticle for selective cancer targeting [J].
Amin, Md. Lutful ;
Kim, Dami ;
Kim, SeJin .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2016, 91 :138-143
[3]  
Amjadi I, 2013, IRAN J PHARM RES, V12, P623
[4]   Blend Microspheres of Poly(3-hydroxybutyrate) and Cellulose Acetate Phthalate for Colon Delivery of 5-Fluorouracil [J].
Chaturvedi, Kiran ;
Kulkarni, Anandrao R. ;
Aminabhavi, Tejraj M. .
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, 2011, 50 (18) :10414-10423
[5]   Preparation and characterization of flurbiprofen-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) microspheres [J].
Coimbra, Patricia A. ;
De Sousa, Herminio C. ;
Gil, Maria H. .
JOURNAL OF MICROENCAPSULATION, 2008, 25 (03) :170-178
[6]   9-nitrocamptothecin polymeric nanoparticles: cytotoxicity and pharmacokinetic studies of lactone and total forms of drug in rats [J].
Dadashzadeh, Simin ;
Derakhshandeh, Katayoun ;
Shirazi, Farshad Hoseini .
ANTI-CANCER DRUGS, 2008, 19 (08) :805-811
[7]   Polymeric nanoparticles for oral delivery of 5-fluorouracil: Formulation optimization, cytotoxicity assay and pre-clinical pharmacokinetics study [J].
de Mattos, Ana Cristina ;
Altmeyer, Clescila ;
Tominaga, Tania Toyomi ;
Khalil, Najeh Maissar ;
Mainardes, Rubiana Mara .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2016, 84 :83-91
[8]   Understanding the correlation between in vitro and in vivo immunotoxicity tests for nanomedicines [J].
Dobrovolskaia, Marina A. ;
McNeil, Scott E. .
JOURNAL OF CONTROLLED RELEASE, 2013, 172 (02) :456-466
[9]   PLGA nanoparticles augmented the anticancer potential of pentacyclic triterpenediol in vivo in mice [J].
Dubey, Ravindra Dhar ;
Saneja, Ankit ;
Qayum, Arem ;
Singh, Amarinder ;
Mahajan, Girish ;
Chashoo, Gousia ;
Kumar, Amit ;
Andotra, Samar S. ;
Singh, Shashank K. ;
Singh, Gurdarshan ;
Koul, Surinder ;
Mondhe, Dilip M. ;
Gupta, Prem N. .
RSC ADVANCES, 2016, 6 (78) :74586-74597
[10]   Microencapsulation of Antibiotic Rifampicin in Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [J].
Duran, N. ;
Alvarenga, M. A. ;
Da Silva, E. C. ;
Melo, P. S. ;
Marcato, P. D. .
ARCHIVES OF PHARMACAL RESEARCH, 2008, 31 (11) :1509-1516