Abstracts Book - IMRC 2018

• SB6-O035
PREPARATION AND IN VITRO EVALUATION OF A SMART DRUG
DELIVERY SYSTEM: ( 177 Lu-DOTA-HA-PLGA(MTX), AS A NEW
POTENTIAL NANORADIOPHARMACEUTICAL FOR COMBINED
THERAPY IN ARTHRITIS
Rosa Maydelid Trujillo Nolasco 1 , Enrique Morales Avila 1 , Blanca Eli Ocampo García 2
1 Universidad Autónoma del Estado de México, Farmacia, Mexico. 2 Instituto Nacional de
Investigaciones Nucleares (ININ), Gerencia de aplicaciones nucleares a la salud, Mexico.
Introduction: Radiosynovectomy is a technique for local treatment of
rheumatoid arthritis (RA), used to decrease inflammation of the synovial tissue
by intraarticular injection of a β-emitting radionuclide into the joint. 177 Lu is
suitable for radiotherapy due to its favourable decay characteristics. Polymeric
nanoparticles encapsulating drugs are a good option to treat several diseases,
including RA. Methotrexate (MTX) has been widely used in the arthritis
treatment. Hyaluronic acid (HA) is specific binding for the CD44 and hyaluronan
receptors overexpressed on the synovial tissue cells. The aim of this research
was to synthesize 177 Lu-DOTA-HA-PLGA(MTX) as a smart drug delivery system
with target-specific recognition useful in radiosynovectomy. Methods: The
polymeric nanoparticle system was prepared by single emulsification-solvent
evaporation method. Conjugation (–HA) was carried out by carbodiimide
reaction, and the quelant agent –DOTA was carried out by HATU reaction,
samples were purified by ultracentrifugation. Physicochemical characterization
was performed by UV-Vis, FT-IR, SEM and DLS. The MTX encapsulation and
loading efficiency were determined by UV-Vis. 177 Lu labelling was performed in
aqueous medium at pH 7.0. Results: The DOTA-HA-PLGA(MTX) nanoparticle
mean diameters was 167.6 nm, whit a monomodal and narrow distribution.
Spectroscopic techniques demonstrated the conjugation of HA to polymeric
nanosystem. The MTX encapsulation was 95.2 % and the loading efficiency was
63.7 %. The radiochemical purity was 96 ± 2 % determined by size-exclusion
radio-HPLC. Conclusion: Radiosynovectomy is a less invasive method compared
to surgical synovectomy and may provide long-term relief of pain and swelling
as well as improvement in joint function. 177 Lu-DOTA-HA-PLGA(MTX) is drug
delivery system, based on biocompatible polymeric PLGA nanoparticles
conjugated to hyaluronic acid 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. 177 Lu-