Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma.

Abstract

In this work, multifunctional lipid nanocapsules (M-LNC) were designed to combine the activity of the cytotoxic drug paclitaxel (PTX) with the immunostimulant CpG. This nanosystem, consisting of modified lipid nanocapsules coated with a cationic polymeric shell composed of chitosan (CS), was able to allocate the hydrophobic drug PTX in the inner oily core, and to associate onto the surface the genetic material CpG. The CS-coated LNC (CS-LNC), showed a narrow size distribution with an average size of 70 nm and a positive zeta potential (+25 mV). They encapsulated PTX in a high amount (98%), and, due to the cationic surface charge, were able to adsorb CpG without losing stability. As a preliminary in vitro study, the apoptotic effect on GL261 glioma cells was investigated. The drug-loaded CS-LNC exhibited the ability to interact with glioma cells and induce an important apoptotic effect in comparison with blank systems. Finally, the M-LNC made of CS-LNC loaded with both CpG and PTX were tested in vivo, injected via convention enhanced delivery (CED) in GL261-glioma-bearing mice. The results showed that the overall survival of mice treated with the M-LNC was significantly increased in comparison with the control, Taxol(®), or the separated injection of PTX-loaded LNC and CpG. This effect was also confirmed by magnetic resonance imaging (MRI) which revealed the reduction of tumor growth in the animals treated with CpG and PTX-loaded M-LNC. All these findings suggested that the developed M-LNC could potentiate both CpG immunopotency and PTX antitumor activity by enhancing its delivery into the tumor microenvironment.

Bioinspired hyaluronic acid and polyarginine nanoparticles for DACHPt delivery

“…All the systems were treated with drugs and nanoparticles diluted with serum free N1 supplemented medium. Serum free N1 supplemented medium was prepared with DMEM with amino acids, 1% antibiotics (10,000 units penicillin, 10 mg streptomycin, 25 μg amphotericin B/mL solubilized in an appropriate citrate buffer), 1% HEPES buffer, 1% NEAA (Non Essential Amino Acid) 100X, 1% sodium pyruvate, 1% N1 medium supplement 100X [33,34]. Cell viability reduction assay was performed using CellTiter 96® AQueous One Solution cell proliferation assay kit containing a tetrazolium compound [3- Evaluation of HMGB1 secretion and ATP release upon incubation of DACHPt-loaded nanoparticles with B6KPC3 cells B6KPC3 cells were plated and treated as described above, with increasing concentrations of DACHPt-loaded NP, oxaliplatin and DACHPt water solution during 24 h. Blank NP were also tested as a control.…”

Targeting experimental orthotopic glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs)

“…[4][5][6][7][8][9][10] Thus, Liu et al 4 showed that chitosan surface-modified poly(lactideco-glycolide)-chitosan nanoparticles (PLGA/CS NPs) loaded with carmustine (bis-chloroethylnitrosourea, BCNU) and its sensitizer (O 6 -benzylguanine, BG) had a strong antitumor effect in the F98 glioma-bearing mice model. In another study by Lollo et al, 11 the authors could demonstrate similar effects with paclitaxel (PTX)-loaded particles in GL261 gliomabearing mice. Subsequent functionalization of the chitosan nanoparticle surface with bioligands further enhanced the ability of the particles to cross the blood-brain barrier (BBB) and their brain tumor accumulation level.…”

Nanopharmaceuticals: A Boon to the Brain-Targeted Drug Delivery

“…Many pre-clinical studies adapted CED to infuse nano-formulations directly into the brain [59]. C57BL/6 J mice were used to infuse a 10 μL solution of lipid nanocapsules (LNCs) having an average size of 70 nm into their skull at an infusion rate of 0.5 μL/min [60]. An alternate method for direct infusion was also reported in which drug-loaded micelles were injected by making small incisions on the skull.…”