This work aims to develop solid
lipid nanoparticles (SLNs) loaded with
retinoic acid (RA) to evaluate the influence of two lipophilic
amines,
stearylamine (SA) and benethamine (BA), and one hydrophilic,
triethylamine (TA), on
drug-encapsulation efficiency (EE) and cytotoxicity in
cancer cell lines. The SLNs were characterized for EE, size, and zeta potential. The mean particle size decreased from 155 ± 1 nm (SLNs without
amine) to 104 ± 4, 95 ± 1, and 96 ± 1 nm for SLNs prepared with SA, BA, and TA, respectively. SA-RA-loaded SLNs resulted in positively charged particles, whereas those with TA and BA were negatively charged. The EEs were significantly improved with the addition of the
amines, and they increased from 36% ± 6% (without
amine) to 97% ± 2%, 90% ± 2%, and 100% ± 1% for SA, TA, and BA, respectively. However, stability studies showed higher EE for BA-RA-loaded SLNs than TA-RA-loaded SLNs after 30 days. The formulations containing SA loaded or unloaded (blank SLNs) with RA were cytotoxic in normal and
cancer cell lines. In contrast, the blank SLNs containing TA or BA did not show cytotoxicity in human breast
adenocarcinoma cells (MCF-7), while RA-loaded SLNs with the respective
amines were significantly more cytotoxic than free RA. Furthermore, the cytotoxicity of BA-RA-loaded SLNs was significantly higher than TA-RA-loaded SLNs. These findings are in agreement with the data obtained in the evaluation of subdiploid
DNA content and cell-cycle analysis, which showed better anticancer activity for BA-RA-loaded SLNs than TA-RA-loaded SLNs and free RA. Taken together, these findings suggest that the BA-RA-loaded SLN formulation is a promising alternative for the
intravenous administration of RA in the treatment of
cancer.