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PEGylated and poloxamer-modified chitosan nanoparticles incorporating a lysine-based surfactant for pH-triggered doxorubicin release.

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      Abstract

      The growing demand for efficient chemotherapy in many cancers requires novel approaches in target-delivery technologies. Nanomaterials with pH-responsive behavior appear to have potential ability to selectively release the encapsulated molecules by sensing the acidic tumor microenvironment or the low pH found in endosomes. Likewise, polyethylene glycol (PEG)- and poloxamer-modified nanocarriers have been gaining attention regarding their potential to improve the effectiveness of cancer therapy. In this context, DOX-loaded pH-responsive nanoparticles (NPs) modified with PEG or poloxamer were prepared and the effects of these modifiers were evaluated on the overall characteristics of these nanostructures. Chitosan and tripolyphosphate were selected to form NPs by the interaction of oppositely charged compounds. A pH-sensitive lysine-based amphiphile (77KS) was used as a bioactive adjuvant. The strong dependence of 77KS ionization with pH makes this compound an interesting candidate to be used for the design of pH-sensitive devices. The physicochemical characterization of all NPs has been performed, and it was shown that the presence of 77KS clearly promotes a pH-triggered DOX release. Accelerated and continuous release patterns of DOX from CS-NPs under acidic conditions were observed regardless of the presence of PEG or poloxamer. Moreover, photodegradation studies have indicated that the lyophilization of NPs improved DOX stability under UVA radiation. Finally, cytotoxicity experiments have shown the ability of DOX-loaded CS-NPs to kill HeLa tumor cells. Hence, the overall results suggest that these pH-responsive CS-NPs are highly potent delivery systems to target tumor and intracellular environments, rendering them promising DOX carrier systems for cancer therapy.

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      Affiliations
      [1 ] Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil.
      [2 ] Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil. Electronic address: daniele.rubert@gmail.com.
      [3 ] Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
      [4 ] Departamento de Tecnología Química y de Tensioactivos, IQAC, CSIC, C/Jordi Girona 18-26, 08034 Barcelona, Spain.
      Journal
      Colloids Surf B Biointerfaces
      Colloids and surfaces. B, Biointerfaces
      Elsevier BV
      1873-4367
      0927-7765
      Feb 01 2016
      : 138
      26674840 S0927-7765(15)30338-6 10.1016/j.colsurfb.2015.11.049

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