Development, Characterization and Cell Viability Inhibition of PVA Spheres Loaded with Doxorubicin and 4 `-Amino-1-Naphthyl-Chalcone (D14) for Osteosarcoma

Author(s):Show less -

Seba, Viviane ^{[1, 2]} ; de Lima, Gabriel Goetten ^{[2, 3]} ; Pereira, Bruno L. ^[3] ; Silva, Gabriel ^[4] ; Reinhardt, Luiza Steffens ^{[5, 6]} ; Arantes, Pablo Ricardo ^[7] ; Chee, Bor Shin ^[2] ; dos Santos, Mariana Bastos ^[8] ; Franca, Suzelei C. ^[1] ; Regasini, Luis Octavio ^[8] ; Fachin, Ana Lucia ^{[1, 9]} ; Cao, Zhi ^[2] ; Nugent, Michael J. D. ^[2] ; Marins, Mozart ^{[1, 9, 10]}

Affiliation

^[1] Univ Ribeirao Preto, Biotechnol Unit, BR-14096900 Ribeirao Preto, SP - Brazil

^[2] Athlone Inst Technol, Mat Res Inst, Athlone, Westmeath - Ireland

^[3] Univ Fed Parana, Post Grad Program Engn & Mat Sci PIPE, BR-81530000 Curitiba, PR - Brazil

^[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, BR-14040900 Ribeirao Preto, SP - Brazil

^[5] Fed Univ Hlth Sci Porto Alegre, Lab Genet Toxicol, BR-90050170 Porto Alegre, RS - Brazil

^[6] Univ Newcastle, Coll Hlth Med & Wellbeing, Hunter Med, Sch Biomed Sci & Pharm, Newcastle, NSW 2308 - Australia

^[7] Univ Calif Riverside, Dept Bioengn, Riverside, CA 92507 - USA

^[8] Sao Paulo State Univ Unesp, Inst Biosci Humanities & Exact Sci, Dept Chem & Environm Sci, Lab Green & Med Chem, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[9] Univ Ribeirao Preto, Med Sch, BR-14096900 Ribeirao Preto, SP - Brazil

^[10] Univ Ribeirao Preto, Pharmaceut Sci Sch, BR-14096900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: POLYMERS; v. 13, n. 16 AUG 2021.
• Web of Science Citations: 0

Abstract

Chalcones (1,3-diaryl-2-propen-1-ones) are naturally occurring polyphenols with known anticancer activity against a variety of tumor cell lines, including osteosarcoma (OS). In this paper, we present the preparation and characterization of spheres (similar to 2 mm) from polyvinyl alcohol (PVA) containing a combination of 4 `-Amino-1-Naphthyl-Chalcone (D14) and doxorubicin, to act as a new polymeric dual-drug anticancer delivery. D14 is a potent inhibitor of osteosarcoma progression and, when combined with doxorubicin, presents a synergetic effect; hence, physically crosslinked PVA spheres loaded with D14 and doxorubicin were prepared using liquid nitrogen and six freeze-thawing cycles. Physical-chemical characterization using a scanning electron microscope (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) presented that the drugs were incorporated into the spheres via weak interactions between the drugs and the polymeric chains, resulting in overall good drug stability. The cytotoxicity activity of the PVA spheres co-encapsulating both drugs was tested against the U2OS human osteosarcoma cell line by 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) assay, and compared to the spheres carrying either D14 or doxorubicin alone. The co-delivery showed a cytotoxic effect 2.6-fold greater than doxorubicin alone, revealing a significant synergistic effect with a coefficient of drug interaction (CDI) of 0.49. The obtained results suggest this developed PVA sphere as a potential dual-drug delivery system that could be used for the prominent synergistic anticancer activity of co-delivering D14 and doxorubicin, providing a new potential strategy for improved osteosarcoma treatment. (AU)

• FAPESP's process: 17/03237-2 - Bioscreening of polyphenols with anticancer activity and investigation of the molecular mechanisms involving the p53 transcription factor
• Grantee: Mozart de Azevedo Marins
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/03074-1 - Exploring the activity of transcription factor Sp1 associated to mesenchymal epithelial transition as a therapeutic target of osteosarcoma
• Grantee: Mozart de Azevedo Marins
• Support Opportunities: Regular Research Grants