Preparation and in vitro evaluation of radiolabeled HA-PLGA nanoparticles as novel MTX delivery system for local treatment of rheumatoid arthritis

被引：67
作者：
Maydelid Trujillo-Nolasco, R. [1 ,2 ]
Morales-Avila, Enrique [1 ]
Ocampo-Garcia, Blanca E. [2 ]
Ferro-Flores, Guillermina [2 ]
Gibbens-Bandala, Brenda, V [1 ,2 ]
Escudero-Castellanos, Alondra [2 ,3 ]
Isaac-Olive, Keila [3 ]
机构：
[1] Univ Autonoma Estado Mexico, Fac Quim, Paseo Tollocan Esq Paseo Colon S-N, Toluca 50120, Estado De Mexic, Mexico
[2] Inst Nacl Invest Nucl, Dept Mat Radiactivos Ocoyoacac Mexico, Ocoyoacac, Mexico
[3] Univ Autonoma Estado Mexico, Fac Med Toluca Mexico, Toluca, Mexico
来源：
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS | 2019年 / 103卷
关键词：
Radiosynovectomy; Smart drug delivery system; Lutetium-177; Methotrexate; Polymeric nanoparticles; Targeted therapy; LU-177-LABELED GOLD NANOPARTICLES; CANCER; PHARMACOKINETICS; INFLAMMATION; EFFICACY; PROVIDE; LU-177; ACID;
D O I：
10.1016/j.msec.2019.109766
中图分类号：
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号：
0805 ; 080501 ; 080502 ;
摘要：
Radiosynovectomy is a technique used to decrease inflammation of the synovial tissue by intraarticular injection of a beta-emitting radionuclide, such as Lu-177, which is suitable for radiotherapy due to its decay characteristics. Drug-encapsulating nanoparticles based on poly lactic-co-glycolic acid (PLGA) polymer are a suitable option to treat several arthritic diseases, used as anti-inflammatory drugs transporters of such as methotrexate (MTX), which has been widely used in the arthritis treatment (RA), and hyaluronic acid (HA), which specifically binds the CD44 and hyaluronan receptors overexpressed on the inflamed synovial tissue cells. The 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was used as complexing agent of Lutetium-177 for radiotherapy porpoises. The aim of this research was to synthesize Lu-177-DOTA-HA-PLGA(MTX) as a novel, smart drug delivery system with target-specific recognition, potentially useful in radiosynovectomy for local treatment of rheumatoid arthritis. The polymeric nanoparticle system was prepared and chemically characterized. The MTX encapsulation and radiolabelling were performed with suitable characteristics for its in vitro evaluation. The HA-PLGA(MTX) nanoparticle mean diameter was 167.6 nm +/- 57.4 with a monomodal and narrow distribution. Spectroscopic techniques demonstrated the effective conjugation of HA and chelating agent DOTA to the polymeric nanosystem. The MTX encapsulation was 95.2% and the loading efficiency was 6%. The radiochemical purity was 96 +/- 2%, determined by ITLC. Conclusion: Lu-177-DOTA-HA-PLGA(MTX) was prepared as a biocompatible polymeric PLGA nanoparticle conjugated to HA for specific targeting. The therapeutic nanosystem is based on bi-modal mechanisms using MTX as a disease-modifying antirheumatic drug (DMARD) and Lu-177 as a radiotherapeutic component. The Lu-177-DOTA-HA-PLGA(MTX) nanoparticles showed properties suitable for radiosynovectomy and further specific targeted anti-rheumatic therapy.
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页数：11
相关论文
共 40 条
[1]   A review of therapeutic challenges and achievements of methotrexate delivery systems for treatment of cancer and rheumatoid arthritis [J].
Abolmaali, Samira Sadat ;
Tamaddon, Ali Mohammad ;
Dinarvand, Rassoul .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2013, 71 (05) :1115-1130
[2]  
Alkrad Yahya Mrestani, 2003, J PHARM BIOMED ANAL, V31, P545, DOI [10.1016/80731-7085(02)00682-9, DOI 10.1016/80731-7085(02)00682-9]
[3]   Synthesis and evaluation of Lys1(α,γ-Folate)Lys3(177Lu-DOTA)-Bombesin(1-14) as a potential theranostic radiopharmaceutical for breast cancer [J].
Aranda-Lara, Liliana ;
Ferro-Flores, Guillermina ;
Azorin-Vega, Erika ;
de Maria Ramirez, Flor ;
Jimenez-Mancilla, Nallely ;
Ocampo-Garcia, Blanca ;
Santos-Cuevas, Clara ;
Isaac-Olive, Keila .
APPLIED RADIATION AND ISOTOPES, 2016, 107 :214-219
[4]   Molecular structure, vibrational spectra and DFT molecular orbital calculations (TD-DFT and NMR) of the antiproliferative drug Methotrexate [J].
Ayyappan, S. ;
Sundaraganesan, N. ;
Aroulmoji, V. ;
Murano, E. ;
Sebastian, S. .
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, 2010, 77 (01) :264-275
[5]   Iron oxide nanoparticles coated with gold: Enhanced magnetic moment due to interfacial effects [J].
Banerjee, S. ;
Raja, S. O. ;
Sardar, M. ;
Gayathri, N. ;
Ghosh, B. ;
Dasgupta, A. .
JOURNAL OF APPLIED PHYSICS, 2011, 109 (12)
[6]   Lutetium-177 Therapeutic Radiopharmaceuticals: Linking Chemistry, Radiochemistry, and Practical Applications [J].
Banerjee, Sharmila ;
Pillai, M. R. A. ;
Knapp, F. F. .
CHEMICAL REVIEWS, 2015, 115 (08) :2934-2974
[7]   Infrared spectroscopy of proteins [J].
Barth, Andreas .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2007, 1767 (09) :1073-1101
[8]  
Burt HM, 2009, EXPERT OPIN DRUG DEL, V6, P17, DOI [10.1517/17425240802647259, 10.1517/17425240802647259 ]
[9]   Advanced nanomedicine for rheumatoid arthritis treatment: focus on active targeting [J].
Chen, Mingli ;
Daddy, Kambere Amerigos J. C. ;
Xiao, Yanyu ;
Ping, Qineng ;
Zong, Li .
EXPERT OPINION ON DRUG DELIVERY, 2017, 14 (10) :1141-1144
[10]   Utilization of nanoparticle technology in rheumatoid arthritis treatment [J].
Dolati, Sanam ;
Sadreddini, Sanam ;
Rostamzadeh, Davoud ;
Ahmadi, Majid ;
Jadidi-Niaragh, Farhad ;
Yousefi, Mehdi .
BIOMEDICINE & PHARMACOTHERAPY, 2016, 80 :30-41
1234