PREPARATION, CHARACTERIZATION AND RADIOLABELED OF VENLAFAXINE-PLGA NANOPARTICLES WITH 99mTC FOR BRAIN DELIVERY

Introduction: Crossing the BBB is a major challenge for the efficient delivery in the brain. Fortunately, exhibits transport mechanisms and there are numerous strategies to cross it. Transferrin (Tf) has been widely applied to... [ view full abstract ]

Introduction: Crossing the BBB is a major challenge for the efficient delivery in the brain. Fortunately, exhibits transport mechanisms and there are numerous strategies to cross it. Transferrin (Tf) has been widely applied to enhance cellular uptake of nanoparticles (NPs) in brain delivery.
To evaluate the biodistribution of nanocarriers, NPs was radiolabeled with radioisotopes for evaluation in organs or tissues after administration.

Methods: NPs were prepared by emulsion solvent evaporation technique. The size and zeta potential (ZP) was measured and the morphology and shape were examined by using transmission electron microscope. The encapsulation efficiency were determined indirectly by HPLC.
After, Tf was conjugated on the surface of NPs using a carbodiimide method with EDC and NHS. Conjugation efficiency was measured indirectly.

For radiolabeled, lyophilized NPs were dispersed in NaCl in vials under vacuum. SnCl2-2-hydrate were dissolved in HCl 37% and was added with ≈74 MBq of 99mTc. Finally, the system was incubated for 10 min.
99mTc -NPs suspensions were analyzed by thin layer chromatography (TLC) with silica gel strips. With 0.9% NaCl as the mobile phase, free pertechnetate ran with the front, meanwhile particles stayed in the start. Using a solution of pyridine:acetic acid:water (3:5:15), radiocolloids remained at start, NPs migrated with Rf = 0.6- 0.8.

Results: The particle size, polydispersity index (PdI) and ZP of NPs were characterized by DSC. NPs had a mean size of 253.02±13.10 nm with a zeta potential of -3.30±1.74 mV. Their PdI of 0.043±0.03. After conjugation, NPs-Tf showed a mean size of 312.94±27.93 nm with a PdI less than 0.2 and a ZP of -2.40±0.56mV. The NPs had an average encapsulation efficiency of up to 65.5±2.65% and the conjugation efficiency was 60.4±3.77. T.E.M. analysis revealed that NPs had a solid structure and spherical shape.

PLGA nanoparticles with Tf and without surface modification were labeled with 99mTc with a yield ≥ 90 % (TLC). After radiolabeling, particles increased in size, ≈ 380 nm.

Discussion: NPs exhibits a suitable size, a high homogeneity, encapsulation and conjugation efficiency.
Radiolabeling process were reproducible and nanosystem is suitable for in vivo theragnosis.