FULL PAPER www.ms-journal.de Encapsulation of Magnetic Nanoparticles and Copaíba Oil in Poly(methyl methacrylate) Nanoparticles via Miniemulsion Polymerization for Biomedical Application Arthur P. Cordeiro, Paulo E. Feuser, Pedro H. H. Araújo, and Claudia Sayer* Polymeric nanoparticles (NPs) are used for drug delivery, mainly due to their ability to increase the selectivity and therapeutic efficacy of the encapsulated molecules. Alternative therapeutic compounds like magnetic nanoparticles (MNPs) and copaiba oil are alternatives for the development of more efficient and less aggressive therapeutic systems. The objective of the present work is to synthesize poly(methyl methacrylate) (PMMA) nanoparticles containing MNPs and copaiba oil (CO) via miniemulsion polymerization. The nanoparticles presented a mean diameter of ≈98 ± 1 nm with narrow particle size dispersion (0.1) and high colloidal stability with zeta potential below -50 ±-3 mV. The miniemulsion polymerization process allowed to incorporate the MNPs and the copaiba oil into the polymer matrix and the nanoparticles presented a saturation magnetization higher than ≈49 emu/g of MNPs and superparamagnetic properties. The evaluated PMMA-MNPs-CO concentrations, up to 200 µg mL -1 of MNPs, did not affect fibroblast cells viability. 1. Introduction In the last years, the necessity to create alternative therapeutic systems to be applied in the pharmaceutical and biomedical ar- eas has increased due to the limited number of treatments and the drug resistance developed by the diseases. [1] The application of co-encapsulated biomolecules and inorganic nanoparticles is a potential strategy to generate new therapeutic effects from the synergic interaction between the therapeutic agents. [1,2] Copaiba oil (CO) is a natural and biocompatible compound approved by the FDA, which has antibacterial, antimicrobial, antifungal, anti- inflammatory, and analgesic properties. [3–5] Magnetic nanoparti- cles (MNPs) are nanostructured systems capable of performing therapeutic and diagnosis functions being capable of delivering drugs to precise targets and be used in hyperthermia treatments in the presence of an external magnetic field. [6,7] These character- istics of MNPs makes it a great potential alternative to decrease drug dosage administration. [8,9] A. P. Cordeiro, P. E. Feuser, P. H. H. Araújo, C. Sayer Departamento de Engenharia Química e Engenharia de Alimentos Universidade Federal de Santa Catarina Florianópolis, Santa Catarina 88040–900, Brazil E-mail: claudia.sayer@ufsc.br DOI: 10.1002/masy.202000112 Polymeric nanoparticles (NPs) are stable colloidal dispersions or solid particles that can be applied as drug delivery system due to desirable properties such as drug pro- tection, increase drug stability and absorp- tion, high encapsulation efficiency, biocom- patibility, lower drug administration and decrease side effects. [10–12] These NPs can be classified as nanocapsules (the encap- sulated compound is confined in a cavity surrounded by a polymeric matrix, obtain- ing a core-shell structure) or nanospheres (the encapsulated compound is dispersed in the polymeric matrix, leading to the formation of a monolithic system), [12–14] which can be prepared via in situ polymer- ization of dispersed monomers or on the precipitation of preformed polymers. [13,15] Miniemulsion polymerization is an in situ technique that uses high shear energy to break the primary organic emulsion into monomers nanodroplets that are nucleated and polymerized, forming the NPs. [16–19] In an ideal system, ev- ery droplet becomes a particle after polymerization; thus, miniemulsion polymerization allows to obtain high levels of drug encapsulation, high polymerization rates, and narrow size distribution. [20,21] Poly(methyl methacrylate) (PMMA) is a well- established non-toxic and safe biomedical material due to its stability and biocompatibility, being used in different biomed- ical applications such as vaccines, dental prosthetics and drug delivery. [15,22–25] Also, PMMA has desirable physicochemical properties to perform a simple and one step miniemulsion poly- merization and simultaneously encapsulate different types of biomolecules and structures in the NPs. [26,27] In this way, the goal of this study was to synthesize and characterize PMMA NPs con- taining MNPs and CO obtained by miniemulsion polymeriza- tion. Lastly, in vitro cytotoxicity assays were performed in embryo mouse fibroblast (NIH3T3) cells. 2. Results and Discussion Drug delivery systems based on NPs require appropriate diam- eter, size distribution (polydispersity index), zeta potential, and morphology to be used as therapeutic agents in biomedicine and pharmaceutics. [28,29] Table 1 present the diameter, size distribu- tion, and zeta potential of the NPs synthesized by the miniemul- sion polymerization approach. Macromol. Symp. 2020, 394, 2000112 © 2020 Wiley-VCH GmbH 2000112 (1 of 5)