Validation of a Janus role of methotrexate-based PEGylated chitosan nanoparticles in vitro

Abstract

Recently, methotrexate (MTX) has been used to target to folate (FA) receptor-overexpressing cancer cells for targeted drug delivery. However, the systematic evaluation of MTX as a Janus-like agent has not been reported before. Here, we explored the validity of using MTX playing an early-phase cancer-specific targeting ligand cooperated with a late-phase therapeutic anticancer agent based on the PEGylated chitosan (CS) nanoparticles (NPs) as drug carriers. Some advantages of these nanoscaled drug delivery systems are as follows: (1) the NPs can ensure minimal premature release of MTX at off-target site to reduce the side effects to normal tissue; (2) MTX can function as a targeting ligand at target site prior to cellular uptake; and (3) once internalized by the target cell, the NPs can function as a prodrug formulation, releasing biologically active MTX inside the cells. The (MTX + PEG)-CS-NPs presented a sustained/proteases-mediated drug release. More importantly, compared with the PEG-CS-NPs and (FA + PEG)-CS-NPs, the (MTX + PEG)-CS-NPs showed a greater cellular uptake. Furthermore, the (MTX + PEG)-CS-NPs demonstrated a superior cytotoxicity compare to the free MTX. Our findings therefore validated that the MTX-loaded PEGylated CS-NPs can simultaneously target and treat FA receptor-overexpressing cancer cells.

Exploiting gelatin nanocarriers in the pulmonary delivery of methotrexate for lung cancer therapy

“…Chemically conjugated NPs showed lower IC50 compared to post loaded NPs, this could be attributed to smaller PS of chemically conjugated NPs which may promote their uptake by the A549 cells (Nagayasu et al, 1999;Kulkarni and Feng, 2013). In addition, MTX is an analogue to folic acid which may promote NPs targeting and receptor mediated endocytosis to over expressed folate receptors in cancerous cells (Luo et al, 2014). Therefore, MTX chemically conjugated NPs were selected for spray drying and DPI preparation.…”

“…This is usually opposed by its severe side effects such as myelosuppression, lung distress, nephrotoxicity and ulcerative colitis. Therefore, many passively and actively targeted nanoparticulate carriers viz gold, carbon and PLGA nanoparticles (NPs) were proposed to overcome these limitations (Seo et al, 2009;Luo et al, 2014;Afshari et al, 2014;Ajmal et al, 2015).…”

In vitro and in vivo evaluation of PEGylated nanoparticles of bendamustine for treatment of lung cancer

“…Absorbance of the formazan solution was measured at 570 nm (650 nm background) on a Spectra Max plate reader. The results were expressed as mean  standard deviation of 3 measurements (Tabatabaei Mirakabad et al 2015, Luo et al 2014). …”

Pegylated Gemcitabine and Methotrexate: In Vitro Cytotoxicity Analysis and in Vivo Drug Release Profiling to Assess Their Enhanced Blood Circulation

“…The solution of the side effects is the attachment of drug with a molecule which enhances its pharmacological properties. Many researchers worked for the methotrexate pegylated nanoparticles which contained chitosan and methotrexate loaded chitosan nanoparticles which contained sodium alginate (9). Nanoparticles which loaded with human serum albumin also synthesized which showed better results as compared to the methotrexate alone (10) but these reactions are much complex.…”