MELANOMA CHEMOTHERAPY TREATMENT USING MODIFIED CELLULOSE-BASED INJECTABLE HYDROGEL COMBINED WITH TEMOZOLOMIDE
Abstract
A local delivery method of an injectable modified cellulose nanofiber hydrogel,
DNCNF PAA 10%, loaded with the chemotherapy drug temozolomide, TMZ, was studied
to investigate the most effective and safest therapy window on duke melanoma 6 (DM6)
and human dermal fibroblast cells (HDF-α). Loaded hydrogel concentrations of 25μM1000μM were administered inside PDMS microcurrent device for 72 hours, removed, cells
stained, and quantified. For the long-term study, treatment was administered for 72 hours,
treatment removed, and cells recovered for 72 hours. The data was quantified using a
fluorescent live/dead cell assay and cells counted. There was a cell death dosage effect seen
after the 250μM TMZ hydrogel treatment as the concentrations increased. The 500μM
TMZ hydrogel had ~7-14% DM6 viability with ~50% HDF-α viability. Dosages higher
than the 500μM TMZ hydrogel treatment and free 500μM TMZ had nonspecific killing of both cell types. The long-term melanoma recovery study showed surviving melanoma have
possible TMZ resistance. The most effective and safest therapy window was DNCNF PAA
10% 500μM-750μM TMZ. Currently, the treatment therapy window found is being studied
further involving co-culturing of both cell types. Future studies recommended are TMZ
resistance studies and in vivo animal studies.