Physicochemical Characterization of PHBV Nanoparticles Functionalized with Multiple Bioactives Designed to be Theranosti

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ORIGINAL PAPER

Physicochemical Characterization of PHBV Nanoparticles Functionalized with Multiple Bioactives Designed to be Theranostics for Lung Cancer Paula Solar1 • Natalia Herrera2 • Diego Cea1 • Sindy Devis1 • Fernando Gonzalez-Nilo3 • Natalia Juica1 • Mabel Moreno1 • Maria Nella Gai4 • Ignacio Brescia5 • Soledad Henrı´quez1,6 Luis Velasquez1



Received: 20 April 2020 / Accepted: 7 October 2020  Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Lung cancer is a neoplasm associated with bacterial infections, main reason, to design a combined chemotherapy and antimicrobial treatment. Due to adverse drug reactions, we designed and synthetized polymer Poly(3-hydroxybutyrate-co3-hydroxyvalerate) (PHBV) nanoparticles loaded with clarithromycin and paclitaxel and Superparamagnetic Iron Oxide Nanoparticles (SPION). Spherical nanoparticles with diameters ranging between 176 ± 19 and 222 ± 68 nm, hydrophilic and had a net negative surface charge were obtained. These nanoparticles can be lyophilized and resuspended in polar environments without affecting their physicochemical characteristics and maintaining their antibacterial activity. Both drugs interacted differently with the polymer, avoiding competition between them and facilitating the simultaneous encapsulation. The paclitaxel loaded in these nanoparticles remains almost completely encapsulated during the first 24 h under physiological conditions, allowing its accumulation and release in sites of high permeability and retention, such as tumors. In summary, these PHBV nanoparticles loaded with clarithromycin, paclitaxel and SPION are a promising drug delivery system for use in theranostics against lung cancer.

3

Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de La Vida, Universidad Andre´s Bello, Santiago, Chile

4

Departamento de Ciencias y Tecnologı´a Farmace´utica, Facultad de Ciencias Quı´micas y Farmace´uticas, Universidad de Chile, Santiago, Chile

5

Fundacio´n Instituto de Investigacio´n Austral, Puerto Varas, Chile

6

Instituto de Investigaciones Materno Infantil (IDIMI), Facultad de Medicina, Universidad de Chile, Santiago, Chile

& Paula Solar [email protected] 1

2

Instituto de Investigacio´n Interdisciplinar en Ciencias Biome´dicas (I3CBSEK), Facultad de Ciencias de la Salud, Universidad SEK, Fernando Manterola 0789, Santiago, Providencia, Chile Facultad de Ciencias Quı´micas y Farmace´uticas, Universidad de Chile, Santiago, Chile

123

P. Solar et al.

Keywords PHBV  Biopolymer nanoparticles  Clarithromycin  Paclitaxel  SPION

Introduction Cancer is one of the leading causes of death worldwide according to the World Health Organization (WHO) and the National Cancer Institute (NIH) of the United States. Cancer causes 9.6 million deaths per year worldwide, of which 1.1 million are caused by lung cancer [1]. Lung cancer is an extremely aggressive neoplasm, and more than 50% of patients die before the first year after being diagn