Atorvastatin-loaded cubosome: a repurposed targeted delivery systems for enhanced targeting against breast cancer.

Cancer ranks as one of the most challenging illnesses to deal with because progressive phenotypic and genotypic alterations in cancer cells result in resistance and recurrence. Thus, the creation of novel medications or alternative therapy approaches is mandatory. Repurposing of old drugs is an attractive approach over the traditional drug discovery process in terms of shorter drug development duration, low-cost, highly efficient and minimum risk of failure. In this study Atorvastatin, a statin drug used to treat abnormal cholesterol levels and prevent cardiovascular disease in people at high risk, was introduced and encapsulated in cubic liquid crystals as anticancer candidate aiming at sustaining its release and achieving better cellular uptake in cancer cells. The cubic liquid crystals were successfully prepared and optimized with an entrapment effieciency of 73.57% ±1.35 and particle size around 200 nm. The selected formulae were effectively doped with radioactive iodine 131I to enable the noninvasive visualization and trafficking of the new formulae. The in vivo evaluation in solid tumor bearing mice was conducted for comparing131I-Atorvastatin solution,131I-Atorvastatin loaded cubosome and 131I-Atorvastatin chitosan coated cubosome. The in vivo biodistribution study revealed that tumor radioactivity uptake of 131I-Atorvastatin cubosome and chitosan coated cubosome exhibited high accumulation in tumor tissues (target organ) scoring ID%/g of 5.67 ± 0.2 and 5.03 ± 0.1, respectively 1h post injection compared to drug solution which recorded 3.09 ± 0.05% 1h post injection. Concerning the targeting efficiency, the target/non target ratio for 131I-Atorvastatin chitosan coated cubosome was higher than that of 131I-Atorvastatin solution and 131I ATV-loaded cubosome at all time intervals and recorded T/NT ratio of 2.908 2h post injection.

Meta-Analysis: A Convenient Tool for the Choice of Nose-to-Brain Nanocarriers.

OBJECTIVES: The intranasal route represents a high promising route of administration aiming for brain delivery. Yet, it represents one of the most difficult and complicated routes. Accordingly, scientists are in a continuous search for novel drug delivery vehicles such as the lipid and polymeric nanoparticles that are apt to enhance the bioavailability of the administered drugs to reach the brain. In this study, a certain number of publications were selected from different databases and literature. Meta-analysis studies using two different algorithms (DerSimonian-Laird and inverse variance) followed aiming to explore the published studies and confirm by evidence the superiority of nanocarriers in enhancing the brain bioavailability of various drugs. Furthermore, the quantitative comparison of lipid versus polymeric nanosystems was performed. METHODS: The area under the curve (AUC) as an important pharmacokinetic parameter extracted from in vivo animal studies was designated as the "effect" in the performed meta-analysis after normalization. Forest plots were generated. KEY FINDINGS AND CONCLUSIONS: The meta-analysis confirmed the augmentation of the AUC after the comparison with traditional preparations such as solutions and suspensions. Most importantly, lipid nanoparticles were proven to be significantly superior to the polymeric counterparts.

A novel serum-stable liver targeted cytotoxic system using valerate-conjugated chitosan nanoparticles surface decorated with glycyrrhizin.

The aim of this study was to target a naturally chemotherapeutic agent: ferulic acid to the liver using a biocompatible and an in vivo stable carrier. Accordingly, chitosan as a biopolymer was modified using a hydrophobic moiety and valeric acid in order to increase its in vivo stability. The structure of the newly synthesized product was confirmed using FT-IR and NMR techniques together with the ninhydrin assay. Ferulic acid was conjugated to the modified nanoparticles that were further characterized for particle size, PDI and zeta potential and subjected to ex vivo stability study in serum and cytotoxicity studies in HepG2 cell lines. Furthermore, the nanoparticles were surface-decorated with glycyrrhizin for active liver targeting. The in vivo biodistribution was experimented using radiolabeling assay where the liver scored the highest accumulation of the glycyrrhizin containing nanoparticles after 6h reaching a value of 13.34%ID/g of the total injected dose of labeled drug compared to drug solution and glycyrrhizin free nanoparticles where the accumulation percent did not exceed 4.19%ID/g and 4.26%ID/g, respectively. As a conclusion, the conducted physico-chemical and biological investigations suggested that the proposed selected system can be efficiently utilized as a successful platform for targeting a natural chemotherapeutic agent viz. ferulic acid to the liver.