Preparation and investigation of indirubin‐loaded SLN nanoparticles and their anti‐cancer effects on human glioblastoma U87MG cells

Abstract

Indirubin, an ingredient in traditional Chinese medicine, is considered as an anti-cancer agent. However, due to its hydrophobic nature, clinical efficiency has been limited. Drug delivery via nanotechnology techniques open new windows toward treatment of cancerous patients. Glioblastoma multiforme (GBM) is the most severe and common type of brain primary tumors. Of common problems in targeting therapies of glioblastoma is the availability of drug in tumoric tissues. In this study, Indirubin loaded solid lipid nanoparticles were prepared and their therapeutic potentials and antitumoric effects were assessed on GBM cell line (U87MG). The SLNs were prepared with Cetyl palmitate and Polysorbat 80 via high-pressure homogenization (HPH) methods in hot mode. Then, properties of SLNs including size, zeta potential, drug encapsulation efficacy (EE %) and drug loading were characterized. SLNs morphology and size were observed using SEM and TEM. The crystalinity of formulation was determined by different scattering calorimetry (DSC). The amount of drug release and antitumor efficiency were evaluated at both normal brain pH of 7.2 and tumoric pH of 6.8. The prapared SLNs had mean size of 130 nm, zeta potential of -16 mV and EE of 99.73%. The results of DSC showed proper encapsulation of drug into SLNs. Drug release assessment in both pH displayed sustain release property. The result of MTT test exhibited a remarkable increment in antitumor activity of Indirubin loaded SLN in comparison with free form of drug and blank SLN on multiform GB. This study indicated that Indirubin loaded SLNs could act as a useful anticancer drugs.

Synergic pro-apoptotic effects of Ferulic Acid and nanostructured lipid carrier in glioblastoma cells assessed through molecular and Delayed Luminescence studies

“…To obtain NLC for the glioblastoma treatment, glyceryl oleate was selected for its bioadhesive properties which together with the well-known role of brij components in increasing drug targeting to the CNS, could enhance nanoparticles crossing through the BBB and selectively destroy tumour cells 49,50 . As reported in different articles, brij-decorated nanoparticles have been demonstrated to increase drug targeting to CNS [51][52][53][54] . On the other side, cetyl palmitate (CP) was selected as solid lipid to exploit its ability in inducing apoptosis 55 , thus turning it to advantage of glioblastoma treatment when using CP as raw material in the production of FA-loaded NLCs.…”

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].…”

“…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]). The liposomes are hollow capsules made of a phospholipid bilayer that encapsulates both hydrophilic and lipophilic drugs (small, <100, large, >100 nm, multi lamellar, >500 nm), and they are by far the most effective for brain drug delivery.…”

“…In another study, BVZ was lipolyzed and encapsulated into PLGA NPs along with trehalose in order to achieve long term stability [20]. Indirubin, a hydrophobic compound to treat glioblastoma multiforme (GBM) due to its anti-tumor and anti-angiogenesis properties, was found to be more effective when delivered via SLN [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].…”

“…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).…”