Inclusion of a pH-responsive amino acid-based amphiphile in methotrexate-loaded chitosan nanoparticles as a delivery strategy in cancer therapy

Abstract

The encapsulation of antitumor drugs in nanosized systems with pH-sensitive behavior is a promissing approach that may enhance the success of chemotherapy in many cancers. The nanocarrier dependence on pH might trigger an efficient delivery of the encapsulated drug both in the acidic extracellular environment of tumors and, especially, in the intracellular compartments through disruption of endosomal membrane. In this context, here we reported the preparation of chitosan-based nanoparticles encapsulating methotrexate as a model drug (MTX-CS-NPs), which comprises the incorporation of an amino acid-based amphiphile with pHresponsive properties (77KS) on the ionotropic complexation process. The presence of 77KS clearly gives a pH-sensitive behavior to NPs, which allowed accelerated release of MTX with decreasing pH as well as pH-dependent membrane-lytic activity. This latter performance demonstrates the potential of these NPs to facilitate cytosolic delivery of endocytosed materials.Outstandingly, the cytotoxicity of MTX-loaded CS-NPs was higher than free drug to MCF-7 tumor cells and, to a lesser extent, to HeLa cells. Based on the overall results, MTX-CS-NPs modified with the pH-senstive surfactant 77KS could be potentially useful as a carrier system for intracellular drug delivery and, thus, a promising targeting anticancer chemotherapeutic agent.

Mesoporous silica nanoparticles functionalized with hyaluronic acid. Effect of the biopolymer chain length on cell internalization

“…Target molecules allow the MSNs to reach the tumor tissue only through a molecular recognition mechanism. Then, once in the internal tissue, the stimuliresponsive capping agent [5,34] permits the release of the drug as a response to internal (change of pH [42][43][44][45], temperature [46][47][48], redox reactions [40,[49][50][51][52]) or external (irradiation with light [53][54][55], magnetic field [55][56][57]) stimuli.…”

Study of Thermal Degradation of PLGA, PLGA Nanospheres and PLGA/Maghemite Superparamagnetic Nanospheres

“…Cancer is a multifaceted and genomically complex disease and rapidly emerging experimental evidence has started to shed light on wide ranging factors which underlie cancer development and progression. Confluence of information suggested various nanotechnological approaches to enhance delivery of anticancer agents to the tumor site [14][15][16][17] . Still, because of the degradation ability of PLGA, these materials can be drug carriers, which will, in turn, be released in these specific locations, thus decreasing the side effects caused by medicines to normal cells [11][12][13] .…”

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).…”