PMID- 31349410
OWN - NLM
STAT- MEDLINE
DCOM- 20191230
LR  - 20191230
IS  - 1873-0191 (Electronic)
IS  - 0928-4931 (Linking)
VI  - 103
DP  - 2019 Oct
TI  - Preparation and in vitro evaluation of radiolabeled HA-PLGA nanoparticles as 
      novel MTX delivery system for local treatment of rheumatoid arthritis.
PG  - 109766
LID - S0928-4931(18)31299-2 [pii]
LID - 10.1016/j.msec.2019.109766 [doi]
AB  - Radiosynovectomy is a technique used to decrease inflammation of the synovial 
      tissue by intraarticular injection of a beta-emitting radionuclide, such as (177)Lu, 
      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 (177)Lu-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: (177)Lu-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 (177)Lu as a radiotherapeutic component. The 
      (177)Lu-DOTA-HA-PLGA(MTX) nanoparticles showed properties suitable for 
      radiosynovectomy and further specific targeted anti-rheumatic therapy.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Trujillo-Nolasco, R Maydelid
AU  - Trujillo-Nolasco RM
AD  - Universidad Autonoma del Estado de Mexico, Facultad de Quimica Toluca-Mexico, 
      Mexico; Instituto Nacional de Investigaciones Nucleares, Departamento de 
      Materiales Radiactivos Ocoyoacac-Mexico, Mexico.
FAU - Morales-Avila, Enrique
AU  - Morales-Avila E
AD  - Universidad Autonoma del Estado de Mexico, Facultad de Quimica Toluca-Mexico, 
      Mexico. Electronic address: emoralesav@uaemex.mx.
FAU - Ocampo-Garcia, Blanca E
AU  - Ocampo-Garcia BE
AD  - Instituto Nacional de Investigaciones Nucleares, Departamento de Materiales 
      Radiactivos Ocoyoacac-Mexico, Mexico.
FAU - Ferro-Flores, Guillermina
AU  - Ferro-Flores G
AD  - Instituto Nacional de Investigaciones Nucleares, Departamento de Materiales 
      Radiactivos Ocoyoacac-Mexico, Mexico.
FAU - Gibbens-Bandala, Brenda V
AU  - Gibbens-Bandala BV
AD  - Universidad Autonoma del Estado de Mexico, Facultad de Quimica Toluca-Mexico, 
      Mexico; Instituto Nacional de Investigaciones Nucleares, Departamento de 
      Materiales Radiactivos Ocoyoacac-Mexico, Mexico.
FAU - Escudero-Castellanos, Alondra
AU  - Escudero-Castellanos A
AD  - Instituto Nacional de Investigaciones Nucleares, Departamento de Materiales 
      Radiactivos Ocoyoacac-Mexico, Mexico; Universidad Autonoma del Estado de Mexico, 
      Facultad de Medicina Toluca-Mexico, Mexico.
FAU - Isaac-Olive, Keila
AU  - Isaac-Olive K
AD  - Universidad Autonoma del Estado de Mexico, Facultad de Medicina Toluca-Mexico, 
      Mexico.
LA  - eng
PT  - Journal Article
DEP - 20190519
PL  - Netherlands
TA  - Mater Sci Eng C Mater Biol Appl
JT  - Materials science & engineering. C, Materials for biological applications
JID - 101484109
RN  - 0 (Radiopharmaceuticals)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 5H0DOZ21UJ (Lutetium)
RN  - 9004-61-9 (Hyaluronic Acid)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Animals
MH  - Arthritis, Rheumatoid/metabolism/pathology/*therapy
MH  - Drug Evaluation, Preclinical
MH  - *Hyaluronic Acid/chemistry/pharmacology
MH  - Isotope Labeling
MH  - *Lutetium/chemistry/pharmacology
MH  - *Methotrexate/chemistry/pharmacology
MH  - Mice
MH  - *Polylactic Acid-Polyglycolic Acid Copolymer/chemistry/pharmacology
MH  - RAW 264.7 Cells
MH  - *Radiopharmaceuticals/chemistry/pharmacology
OTO - NOTNLM
OT  - Lutetium-177
OT  - Methotrexate
OT  - Polymeric nanoparticles
OT  - Radiosynovectomy
OT  - Smart drug delivery system
OT  - Targeted therapy
EDAT- 2019/07/28 06:00
MHDA- 2019/12/31 06:00
CRDT- 2019/07/28 06:00
PHST- 2018/06/06 00:00 [received]
PHST- 2019/01/09 00:00 [revised]
PHST- 2019/05/16 00:00 [accepted]
PHST- 2019/07/28 06:00 [entrez]
PHST- 2019/07/28 06:00 [pubmed]
PHST- 2019/12/31 06:00 [medline]
AID - S0928-4931(18)31299-2 [pii]
AID - 10.1016/j.msec.2019.109766 [doi]
PST - ppublish
SO  - Mater Sci Eng C Mater Biol Appl. 2019 Oct;103:109766. doi: 
      10.1016/j.msec.2019.109766. Epub 2019 May 19.