Modulation of surface charge, particle size and morphological properties of chitosan–TPP nanoparticles intended for gene delivery

Gan, Quan; Wang, Tao; Cochrane, Colette; McCarron, Paul A.

doi:10.1016/j.colsurfb.2005.06.001

Cited by 790 publications

(608 citation statements)

References 19 publications

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“…Before NP preparation, the pH of CS solution was set at 5.5, as at this pH the NPs were smaller and have higher ZP (Gan et al 2005), suggesting their greater stability. Additionally, about 90% of the amino groups of CS (pKa = 6.5) are protonated at pH 5.5 (Mao et al 2010), which ensures that the crosslinking process takes place to form CS-NPs.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2015

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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.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2015

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“…The ionotropic gelation technique is one of the most widely used of a variety of methods to prepare CS-NPs [1,2,6,7]. This procedure is based on reversible crosslinking by electrostatic interaction (between protonized -NH 3 + and an anion such as tripolyphosphate), instead of chemical crosslinking.…”

Section: Introductionmentioning

confidence: 99%

In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

et al. 2013

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Nanoparticles with pH-sensitive behavior may enhance the success of chemotherapy in many cancers by efficient intracellular drug delivery. Here, we investigated the effect of a bioactive surfactant with pH-sensitive properties on the antitumor activity and intracellular behavior of methotrexate-loaded chitosan nanoparticles (MTX-CS-NPs). NPs were prepared using a modified ionotropic complexation process, in which was included the surfactant derived from N α ,N ε -dioctanoyl lysine with an inorganic lithium counterion. The pH-sensitive behavior of NPs allowed accelerated release of MTX in an acidic medium, as well as membrane-lytic pH-dependent activity, which facilitated the cytosolic delivery of endocytosed materials. Moreover, our results clearly proved that MTX-CS-NPs were more active against the tumor HeLa and MCF-7 cell lines than the free drug. The feasibilty of using NPs to target acidic tumor extracellular pH was also shown, as cytotoxicity against cancer cells was greater in a mildly acidic environment. Finally, the combined physicochemical and pH-sensitive properties of NPs generally allowed the entrapped drug to induce greater cell cycle arrest and apoptotic effects. Therefore, our overall results suggest that pH-sensitive MTX-CS-NPs could be potentially useful as a carrier system for tumor and intracellular drug delivery in cancer therapy.

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“…Several strategies involving nanosized carriers for photosensitizer delivery such as liposomes, polymeric micelles, metal-based or silica-based nanoparticles have already been explored [15][16][17][18]. The preparation of chitosan-based hydrophilic nanogels has been widely described in the literature, employing penta sodium triphosphate (PSTP) as the complexing anionic molecule for the polycation chitosan [19][20][21][22][23][24][25]. Chitosan-based nanogels have been studied as carriers of oligonucleotides in gene therapy, for mucosal vaccination, in tissue engineering or drug delivery [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Chitosan-based nanogels for selective delivery of photosensitizers to macrophages and improved retention in and therapy of articular joints

Schmitt

Lagopoulos

Käuper³

et al. 2010

Journal of Controlled Release

111

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Macrophages play key roles in inflammatory disorders. Therefore, they are targets of treatments aiming at their local destruction in inflammation sites. However, injection of low molecular mass therapeutics, including photosensitizers, in inflamed joints results in their rapid efflux out of the joints, and poor therapeutic index. To improve selective uptake and increase retention of therapeutics in inflamed tissues, hydrophilic nanogels based on chitosan, of which surface was decorated with hyaluronate and which were loaded with one of three different anionic photosensitizers were developed. Optimal uptake of these functionalized nanogels by murine RAW 264.7 or human THP-1 macrophages as models was achieved after b 4 h incubation, whereas only negligible uptake by murine fibroblasts used as control cells was observed. The uptake by cells and the intracellular localization of the photosensitizers, of the fluorescein-tagged chitosan and of the rhodamine-tagged hyaluronate were confirmed by fluorescence microscopy. Photodynamic experiments revealed good cell photocytotoxicity of the photosensitizers entrapped in the nanogels. In a mouse model of rheumatoid arthritis, injection of free photosensitizers resulted in their rapid clearance from the joints, while nanogel-encapsulated photosensitizers were retained in the inflamed joints over a longer period of time. The photodynamic treatment of the inflamed joints resulted in a reduction of inflammation comparable to a standard corticoid treatment. Thus, hyaluronate-chitosan nanogels encapsulating therapeutic agents are promising materials for the targeted delivery to macrophages and long-term retention of therapeutics in leaky inflamed articular joints.

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Modulation of surface charge, particle size and morphological properties of chitosan–TPP nanoparticles intended for gene delivery

Cited by 790 publications

References 19 publications

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

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

In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

Chitosan-based nanogels for selective delivery of photosensitizers to macrophages and improved retention in and therapy of articular joints

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