5-Fluorouracil shell-enriched solid lipid nanoparticles (SLN) for effective skin carcinoma treatment.

Khallaf, R. A., H. F. Salem, and A. A. Elbary, "5-Fluorouracil shell-enriched solid lipid nanoparticles (SLN) for effective skin carcinoma treatment.", Drug delivery, vol. 23, issue 9, pp. 3452-3460, 2016 Nov.


CONTEXT: The effective treatment of skin carcinoma is warranted for targeting the chemotherapeutic agents into tumor cells and avoiding unwanted systemic absorption.

OBJECTIVE: This work was dedicated to the purpose of engineering highly penetrating shell-enriched nanoparticles that were loaded with a hydrophilic chemotherapeutic agent, 5-fluorouracil (5-FU).

METHODS: Varying ratios of lecithin and poloxamer188 were used to produce shell-enriched nanoparticles by enabling the formation of reversed micelles within this region of the SLN. The localization of 5-FU within the shell region of the SLN, was confirmed using 5-FU nanogold particles as a tracer. SLN were introduced within sodium carboxy methylcellulose hydrogel, and then applied onto the skin of mice-bearing Ehrlich's ascites carcinoma. The mice were treated with the gel twice daily for 6 weeks.

RESULTS: The transmission electron microscope (TEM) revealed the formation of uniform nanoparticles, which captured reversed micelles within their shell region. The SLNs' had particle size that ranged from 137 ± 5.5 nm to 800 ± 53.6, zeta potential of -19.70 ± 0.40 mV and entrapment efficiency of 47.92 ± 2.34%. The diffusion of the drug-loaded SLN (269.37 ± 10.92 μg/cm(2)) was doubled when compared with the free drug (122 ± 3.09 μg/cm(2)) when both diffused through a hydrophobic membrane. SLN-treated mice exhibited reduced inflammatory reactions, with reduced degrees of keratosis, in addition to reduced symptoms of angiogenesis compared to 5-FU-treated mice.

CONCLUSION: SLN possesses the capacity to be manipulated to entrap and release hydrophilic antitumor drugs with ease.