Oxaliplatin immuno hybrid nanoparticles for active targeting: an approach for enhanced apoptotic activity and drug delivery to colorectal tumors

Abstract

Tumor necrosis factor related apoptosis inducing ligand (TRAIL) proved to be a promising new target for colorectal cancer treatment. Elevated expression of TRAIL protein in tumor cells distinguishes it from healthy cells, thereby delivering the drug at the specific site. Here, we formulated oxaliplatin immunohybrid nanoparticles (OIHNPs) to deliver oxaliplatin and anti-TRAIL for colorectal cancer treatment in xenograft tumor models. The polymeric chitosan layer binds to the lipid film with the mixture of phospholipids by an ultra sound method followed by conjugating with thiolated antibody using DSPE-PEG-mal3400, resulting in the formation of OIHNPs. The polymer layer helps in more encapsulation of the drug (71 ± 0.09%) with appreciable particle size (95 ± 0.01 nm), and lipid layer prevents degradation of the drug in serum by preventing nanoparticle aggregation. OIHNPs have shown a 4-fold decrease in the IC50 value compared to oxaliplatin in HT-29 cells by the MTT assay. These immunonanoparticles represent the successful uptake and internalization of oxaliplatin in HT-29 cells rather than in MCF-7 cells determined by triple fluorescence method. Apoptotic activity in vitro of OIHNPs was determined by the change in the mitochondria membrane potential that further elevates its anti-tumor property. Furthermore, the conjugated nanoparticles can effectively deliver the drug to the tumor sites, which can be attributed to its ability in reducing tumor mass and tumor volume in xenograft tumor models in vivo along with sustaining its release in vitro. These findings indicated that the oxaliplatin immuno-hybrid nanoparticles would be a promising nano-sized active targeted formulation for colorectal-tumor targeted therapy.

Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery

“…In addition, the release characteristic of the drug-loaded OA-CNPs ensures the release in the tumor cells (lower pH than the normal). 52 As shown in Table 2, the PTX and QUE release mechanism from PMs was set up and estimated by some mathematical models. The optimal model of the fitting was obtained with the Korsmeyer-Peppas model.…”

Improved anti-tumor activity of oxaliplatin by encapsulating in anti-DR5 targeted gold nanoparticles

“…Nanoparticles were freeze dried prior to the evaluation of their drug content and entrapment percentage (Tummala et al, 2015). The freeze-dried nanoparticles (20 mg) coat was made to dissolve by adding them to specific solvent (10 ml).…”

“…Apart from its potential cytotoxic activity, oxaliplatin poses side effects such as acute dysthesias, peripheral distal neurotoxicity, myelosupression, etc., resulting in lack of appreciable therapeutic activity. This lack of therapeutic activity and side effects can be attributed to its nonspecific biodistribution (Jia et al, 2009;Tummala et al, 2014;Tummala et al, 2015).…”

5-Fluorouracil enteric-coated nanoparticles for improved apoptotic activity and therapeutic index in treating colorectal cancer

“…IC 50 is the concentration that can inhibit 50% of cell growth was calculated by SPSS software Version 19.0 (SPSS Inc., Chicago, IL). Along with that relative cell viability was calculated for different concentrations for all the samples, which was compared to the untreated control (Tummala et al, 2015a).…”

“…The pellets formed were dried properly at 35-40 C prior to enteric coating using a conventional coating pan (rotating speed at 20 rpm, atomizing air pressure of 2 bar, inlet air temperature of 60-70 C and outlet air temperature of 35-40 C). Eudragit S100 with ammonia and triethyl citrate (coating solution) was sprayed through 1.1 mm spray nozzle to prepare entericcoated pellets (Tummala et al, 2014(Tummala et al, , 2015a.…”