In vivo and in vitro per se effect evaluation of Polycaprolactone and Eudragit® RS100-based nanoparticles

Biodegradable polymeric nanocapsules (NC) present incredible characteristics as drug nanocarriers that optimize drug targeting. However, However, a more detailed isolated effect of polymer-based nanoparticles as drug carriers is required. This work aimed to evaluate the per se effect of blank-NC (NC-B) with different surface characteristics both in vitro and in vivo toxicity. NC1-B (Polysorbate 80 coated poly(ɛ-caprolactone) NC), NC2-B (polyethylene glycol 6000 coated poly(ɛ-caprolactone) NC), NC3-B (chitosan-coated poly(ɛ-caprolactone) NC) and NC4-B (Eudragit® RS100 NC) were prepared by nanoprecipitation method. Formulations were characterized by particle size, zeta potential, and pH. The in vitro cytotoxicity tests against tumor cell lines were performed (HepG2 and MCF-7).

Highlights

• NC were stable during the 30 days analyzed.
• The NC regardless of the coating used, did not demonstrate toxicity against the evaluated cell lines HepG2 and MCF-7.
• The treatment with NC4-B proved to be selective against KOS HSV-1 strains.
• The neurological effects in a stereotyping model in general are low, but they can occur in an isolate way, according to the administered NC-B or evaluated parameter.

Antiviral activity was evaluated by MTT in Vero cells infected with HSV-1 (KOS strain). In vivo evaluation was performed in apomorphine-induced stereotypy in Wistar rats and locomotor activity distance, head movements, and rearing behavior were measured. NC1-B, NC2-B, NC3-B, and NC4-B had a diameter under 350 nm. The pH and zeta potential of formulations varied according to their coating. For in vitro evaluation of antitumor activity and antiviral activity, one-way ANOVA showed no significant differences in cell viability. In vivo tests showed low neurological effects. In conclusion, different surface characteristics of NC-B did not demonstrate toxicity against the evaluated cell lines HepG2 and MCF-7, antiviral effect against HSV-1, and the neurological effects in a stereotyping model were low and may be attributed to the per se effect of NC-B.

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Materials

Poly (ɛ-caprolactone) (PCL, Mw = 80,000 g.mol−1), caprylic/capric triglyceride oil (MCT), sorbitan monostearate (Span® 60), polysorbate 80 (P80), low molecular weight chitosan (CS), Eudragit® RS100 (EUD) and polyethylene glycol 6000 (PEG) were purchased from Sigma-Aldrich (USA). All other chemicals and solvents utilized were of analytical grade. Phosphate buffered saline (PBS), 2,5-diphenyl-3,-(4,5-dimethyl-2-thiazolyl) tetrazolium bromide (MTT), dimethyl sulfoxide (DMSO) and trypsin-EDTA solution (0.5 g porcine trypsin and 0.2 g EDTA • 4Na per liter of Hanks′ Balanced Salt Solution) were obtained from Sigma-Aldrich (USA). Fetal bovine serum (FBS) and Dulbecco’s Modified Eagle’s Medium (DMEM), supplemented with L-glutamine (584 mg/L) and antibiotic/antimycotic (50 mg/mL gentamicin sulfate and 2 mg/L amphotericin B), were purchased from Vitrocell (Brazil).

Renata Bem dos Santos, Ana Claudia Funguetto-Ribeiro, Tamara Ramos Maciel, Dyenefer Pereira Fonseca, Fernanda Reis Favarin, Daniele Rubert Nogueira-Librelotto, Marcelo Gomes de Gomes, Tania Ueda Nakamura, Clarice Madalena Bueno Rolim, Sandra Elisa Haas, In vivo and in vitro per se effect evaluation of Polycaprolactone and Eudragit® RS100-based nanoparticles, Biomedicine & Pharmacotherapy, Volume 153, 2022, 113410, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2022.113410.