abstract
Melanoma often requires adjuvant therapy to combat tumor proliferation and metastasis. In this context, microneedle systems (MNs) present a promising avenue for minimally invasive delivery of drugs or bioactive compounds with natural anticancer properties, targeting the deeper layers of the skin. Herein, we describe the fabrication of bioactive dissolving microneedles composed of carboxymethylcellulose (CMC) and fucoidan (Fuc) using a simple and eco-friendly micromolding technique. The microneedles showcased integral bodies and sharp tips with heights of 456 mu m, and robust mechanical properties, reaching a maximum force of 1.07 N needle-1. Preliminary insertion tests in a polymeric skin model demonstrated the ability of CMC_Fuc MNs to penetrate up to 381 mu m, further validated in ex vivo human skin samples with insertion depths of 325-453 mu m. Dissolution studies in an agarose hydrogel skin model revealed the complete dissolution of the MNs tips within 12 min. In vitro cytotoxicity assays unveiled the antitumoral effect of the CMC_Fuc MNs on A375 melanoma cells, leading to a significant cell viability reduction in both a 2D cell culture (ca. 83 %) and a 3D bioprinted melanoma culture model (ca. 56 %), after 48 h. The CMC_Fuc microneedle systems show great promise for minimally invasive adjuvant treatment of melanoma.
keywords
SULFATED POLYSACCHARIDES; CELLULOSE
subject category
Biochemistry & Molecular Biology; Chemistry; Polymer Science
authors
Silva, ACQ; Teixeira, MC; Jesus, A; Costa, PC; Almeida, IF; Dias-Pereira, P; Correia-Sá, I; Oliveira, H; Silvestre, AJD; Vilela, C; Freire, CSR
our authors
Ana Cristina Quintans da Silva
Junior Researcher
Armando Jorge Domingues Silvestre
Full professor
Carla Vilela
Assistant Professor
Carmen Sofia da Rocha Freire Barros
Coordinating Researcher
Helena Oliveira
Post-Doc FellowshipProjects
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
acknowledgements
This work was developed within the scope of the project CICECO--Aveiro Institute of Materials, UIDB/50011/2020 (DOI 10.544 99/UIDB/50011/2020) , UIDP/50011/2020 (DOI 10.54499/UIDP/5 0011/2020) & LA/P/0006/2020 (DOI 10.54499/LA/P/0006/2020) , CESAM (UIDP/50017/2020 & UIDB/50017/2020 & LA/P/0094/2020) , UCIBIO (UIDP/04378/2020 & UIDB/04378/2020) and i4HB (LA/P/0140/2020) , financed by national funds through the FCT/MCTES (PIDDAC) . FCT is also acknowledged for the doctoral grants to A.C.Q.S. (SFRH/BD/140230/2018 and COVID/BD/152979/2022, DOI: 10.5 4499/COVID/BD/152979/2022) and A.J (UI/BD/151319/2021, DOI 10.54499/UI/BD/151319/2021) , and the research contracts under Scientific Employment Stimulus to H.O. (CEECIND/04050/2017) , C.V. (DOI 10.54499/2021.01571.CEECIND/CP1659/CT0024) and C.S.R.F. (DOI 10.54499/CEECIND/00464/2017/CP1459/CT0033) .