In vitro and in vivo evaluation of cubosomes containing 5-fluorouracil for liver targeting

Abstract

The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic anticancer drug 5-fluorouracil (5-FU) for liver targeting. Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of Poloxamer 407 as a stabilizer. Cubosomes loaded with 5-FU were characterized in vitro and in vivo. In vitro, 5-FU-loaded cubosomes entrapped 31.21% drug and revealed nanometer-sized particles with a narrow particle size distribution. In vitro 5-FU release from cubosomes exhibited a phase of rapid release of about half of the entrapped drug during the first hour, followed by a relatively slower drug release as compared to 5-FU solution. In vivo biodistribution experiments indicated that the cubosomal formulation significantly (P<0.05) increased 5-FU liver concentration, a value approximately 5-fold greater than that observed with a 5-FU solution. However, serum serological results and histopathological findings revealed greater hepatocellular damage in rats treated with cubosomal formulation. These results demonstrate the successful development of cubosomal nanoparticles containing 5-FU for liver targeting. However, further studies are required to evaluate hepatotoxicity and in vivo antitumor activity of lower doses of 5-FU cubosomal formulation in treatment of liver cancer.

Mucin-1-Antibody-Conjugated Mesoporous Silica Nanoparticles for Selective Breast Cancer Detection in a Mucin-1 Transgenic Murine Mouse Model

“…The data indicated that the retro-orbital administration of ab-tMUC1-NIR-MSNs and further accumulation in liver after 8 days did not affect any of the parameters indicative of liver functions with the exception of a decrease in alkaline phosphatase activity and ALT. More importantly, the key markers of liver dysfunction or damage, 57 which are increases in AST or ALT concentrations were not observed. The data from Table II, together with previous reports demonstrated that ab-tMUC1-NIR-MSN nanoprobe is safe during a short-term period and it can be a promising candidate as optical contrast imaging nanoprobe for in vivo applications.…”

Preparation and Characterization of SN-38-Encapsulated Phytantriol Cubosomes Containing α-Monoglyceride Additives

“…The addition of 10% lauric acid or myristic acid to PHYT led to the formation of distinct Bragg peaks with relative positions at spacing ratios of 1 : 3 : 4 . These peaks could be indexed as Miller indices (hk)=(10), (11) and (20) with two-dimensional hexagonal 31,33) lattice parameters of 45.2 and 45.1 Å for the lauric acid and myristic acid additives, respectively (Fig. 4).…”

“…Nanoparticles have been used to encapsulate a wide variety of poorly water-soluble drugs, leading to dramatic improvements in their solubility, stability and drug-targeting properties, as well as reducing any adverse effects. [10][11][12][13] Furthermore, nanoparticles-based drug delivery systems can preferentially target tumors by taking advantage of the enhanced permeability and retention (EPR) effect. 14) A broad range of drug delivery systems, including PEGylated conjugates, polymer micelles, liposome formulations and dendrimers, have been extensively investigated for the formulation of SN-38 to improve its water solubility and bioavailability.…”

Novel piperine-loaded Tween-integrated monoolein cubosomes as brain-targeted oral nanomedicine in Alzheimer&rsquo;s disease: pharmaceutical, biological, and&nbsp;toxicological studies

“…The gold standard steric stabilizer for the preparation of LCN is poloxamer 407. 24,45 Poloxamer 407 is composed of polyethylene oxide (PEO)-polypropylene oxide-PEO block copolymer.…”