Solid Lipid Nanoparticles By Coacervation Loaded With a Methotrexate Prodrug: Preliminary Study for Glioma Treatment

Abstract

Biodistribution studies in healthy rats assessed the superiority of ApoE-conjugated formulation, which was tested on an F98/Fischer glioma model. Differences were observed in tumor growth rate (measured by MRI) between control and treated rats. In vitro tests on F98 cultured cells assessed their susceptibility to treatment, with consequent apoptosis, and allowed us to explain the apoptosis observed in glioma models.

Lab-On-A-Chip for the Development of Pro-/Anti-Angiogenic Nanomedicines to Treat Brain Diseases

“…More importantly, they can be specifically functionalized to target particular pathways and sites on the BMECs. They are designed to have greater BBB permeability [2,6,9,11,17,19], stability [5,9], half-life [11,18,82,83] and shelf-life [5], high-site specific targeting [10,14,84], and a controlled load-release of drugs [18,19,21,84,85].…”

“…These carriers can be functionalized with specific peptides and proteins, to exploit the endocytosis pathways and also be targeted to specific regions of brain. Simply by encapsulating the drugs into a nano-capsule, the drug was able to cross the BBB [6,18]. The SLNs are spherical solid lipid cores, that can encapsulate hydrophilic molecules, the core is made of triglycerides, fatty acids and waxes, and their size ranges from 400 to 1000 nm [6].…”

“…Simply by encapsulating the drugs into a nano-capsule, the drug was able to cross the BBB [6,18]. The SLNs are spherical solid lipid cores, that can encapsulate hydrophilic molecules, the core is made of triglycerides, fatty acids and waxes, and their size ranges from 400 to 1000 nm [6]. They are preferred for their higher drug loading capacity, best production scalability and longer shelf-life (SLNs are stable for 45 days, at 4 • C [5]).…”

“…Similarly, SLN functionalized with apolipoprotein E (ApoE), a suppressor of angiogenesis and cell invasion, was found to show a greater cellular intake when compared to non-functionalized SLNs [7]. In another study, methotrexate (MTX), an anti-angiogenic prodrug-loaded SNPs conjugated with ApoE, were found to have a superior biodistribution in the brain, when compared to bolus delivery of MTX [6]. Further, TMZ, an anti-angiogenic drug used to treat GBM is fast degrading and difficult to direct specified therapeutic dosages to targeted regions.…”

“…Recently, NMs have been investigated for their efficacy in treating brain angiogenesis conditions. These have included nano-capsules, such as solid lipid nanoparticles (SLNs) [4][5][6][7][8], liposomes [9][10][11][12][13][14][15][16], exosomes [17], and others [18], as well as nano-scaffolds made of chitosan [19], polymers [20,21], inorganic nanoparticles (NPs) [22][23][24], etc. (see Table 1).…”