Abstract:
Osteosarcoma (OS) is a rare, aggressive bone tumor that impacts mostly children and young adults. Despite numerous therapeutic efforts, OS still presents low patient survival rate, high metastasis, and relapse occurrence1. To surpass that, polymeric micelles have been researched for the targeted co-delivery of genetic material and drugs.
In this work, mixed polymeric micelles with cationic properties containing polyethyleneimine (PEI), Pluronics® F68 and P123 were prepared. For this purpose, Pluronic® F68 was activated by the addition of diacrylate groups in the two hydroxyl groups at the ends of the Pluronic chain and conjugated with PEI. The prepared nanosystem was structurally characterized by FTIR and NMR spectroscopy and the morphology was assessed by TEM. Following this, Pluronic® P123 was incorporated in the formulation in a ratio of 2:1 regarding the concentration of Pluronic® F68-PEI and Pluronic® P123. Particle size, polydispersity index (PDI) and zeta potential were assessed by Dynamic and Electrophoretic Light Scattering, respectively. The morphology was evaluated by TEM.
Pluronic® F68 diacrylate conjugated with PEI was synthesized successfully as confirmed by FTIR and NMR analysis. It was possible to observe small-sized micelles (around 153 nm) with a PDI of 0.346 and zeta potential of 12.59 mV with irregular spherical shape, a darker core and a lighter shell. The incorporation of Pluronic® P123 in the formulation lowered particle size (119.6 nm) and resulted in spherical micelles. However, zeta potential decreased (7.3 mV) due the presence of Pluronic® P123, but remained positive.
A mixed polymeric micelle composed of Pluronics® F68 and P123 complexed with PEI was developed and characterized, allowing to achieve a stable, small-sized nanosystem, characteristics that suggest a capability to surpass multidrug resistance and perform active targeting. Further incorporation of miRNA145 in the outer cationic shell will be tested for the capacity to inhibit OS metastasis and proliferation.
Key-words: mixed polymeric micelles; polyethyleneimine; Pluronic® F68; Pluronic®P123; Osteosarcoma
References:
1 Melim, C.; Jarak, I.; Veiga, F.; Figueiras, A. The potential of micelleplexes as a therapeutic strategy for osteosarcoma disease. 3 Biotech (2020), 10(4), 147. DOI: 10.1007/s13205-020-2142-5
Funding:
This work received financial support from National Funds (FCT/MEC, Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência) through the project UID/QUI/50006/2013, co-financed by European Union (FEDER under the Partnership Agreement PT2020). It was also supported by the grant FCT PTDC/BTM-MAT/30255/2017 (POCI-01- 0145-FEDER-030255) from the Portuguese Foundation for Science and Technology (FCT) and the European Community Fund (FEDER) through the COMPETE2020 program.
