Methotrexate Nanoparticles Prepared with Codendrimer from Polyamidoamine (PAMAM) and Oligoethylene Glycols (OEG) Dendrons: Antitumor Efficacy in Vitro and in Vivo

Abstract

The novel methotrexate-loaded nanoparticles (MTX/PGD NPs) prepared with amphiphilic codendrimer PGD from polyamidoamine and oligothylene glycol dendrons were obtained via antisolvent precipitation method augmented by ultrasonication. Based on the excellent hydrophility of PGD, the drug-loaded nanoparticles could be investigated easily with the high drug-loading content (~85.2%, w/w). The MTX/PGD NPs possessed spherical morphology, nanoscaled particle size (approximately 182.4 nm), and narrow particle size distribution. Release of MTX from MTX/PGD NPs showed a sustained release manner and completed within 48 h. Hemolytic evaluation indicated MTX/PGD NPs presented good blood compatibility, and the cytotoxicity of nanoparticles against breast cancer cells in vitro, biodistribution in tumor tissue, and antitumor efficacy in vivo were enhanced significantly compared to MTX injection. According to the higher drug-loading content, enhanced antitumor efficacy, and appropriate particle size, MTX/PGD NPs as the drug delivery systems could have potential application for cancer chemotherapy in clinic.

Poly‐allylamine hydrochloride and fucoidan‐based self‐assembled polyelectrolyte complex nanoparticles for cancer therapeutics

“…From Figure , it would reach rapidly to the effective concentration of drug owing to the burst release in the course of 12 h and keep the release sustained then after. Several studies reported the sustained release of MTX‐loaded nanoparticles,and biphasic release of gentamicin from chitosan/fucoidan nanoparticles revealing that our results were in agreement with these reports …”

“…Several studies reported the sustained release of MTX-loaded nanoparticles,and biphasic release of gentamicin from chitosan/fucoidan nanoparticles revealing that our results were in agreement with these reports. 4,34 L929 cells are a kind of mouse fibroblast that is often used to evaluate the biocompatibility of materials due to the short cell cycle and great cell activity. Then, we reported the biocompatibility using L929 cells' viability measurement.…”

Production and Characterization of Chitosan–Polyanion Nanoparticles by Polyelectrolyte Complexation Assisted by High-Intensity Sonication for the Modified Release of Methotrexate

“…Currently, methotrexate (MTX) is widely used as monotherapy or in combination with other anticancer drugs for the treatment of several cancer types, such as brain tumors, primary central nervous system lymphoma, and leptomeningeal metastatic cancer [5,6]. However, the use of MTX is limited due to its poor solubility, non-specific drug delivery and toxic side effects, which leads to disruption of the anticancer treatment for the patient [7]. Nanocarriers, as chemotherapeutic agents, offer novel strategies (i.e., liposomes, polymeric and inorganic nanoparticles, micelles, dendrimers and carbon nanotubes) for targeting cancer cells and tumor zones without causing major damage to the surrounding healthy tissue, and hence, they allow the chemotherapeutic agent to accumulate in tumor zones due to their enhanced permeation and retention effect [8,9].…”

Poloxamer 407 based-nanoparticles for controlled release of methotrexate

“…Many nanodevices have been studied for the encapsulation and release of MTX, however most of the strategies revealed the release of all the drug content after 48 h (Karasulu et al, 2007;Nogueira et al, 2016;Zhao et al, 2016).…”