Nanoparticles incorporating pH-responsive surfactants as a viable approach to improve the intracellular drug delivery.
The pH-responsive delivery systems have brought new advances in the field of functional nanodevices and might allow more accurate and controllable delivery of specific cargoes, which is expected to result in promising applications in different clinical therapies. Here we describe a family of chitosan-TPP (tripolyphosphate) nanoparticles (NPs) for intracellular drug delivery, which were designed using two pH-sensitive amino acid-based surfactants from the family N(α),N(ε)-dioctanoyl lysine as bioactive compounds. Low and medium molecular weight chitosan (LMW-CS and MMW-CS, respectively) were used for NP preparation, and it was observed that the size distribution for NPs with LMW-CS were smaller (~168 nm) than that for NPs prepared with MMW-CS (~310 nm). Hemolysis assay demonstrated the pH-dependent biomembrane disruptional capability of the constructed NPs. The nanostructures incorporating the surfactants cause negligible membrane permeabilization at pH7.4. However, at acidic pH, prevailing in endosomes, membrane-destabilizing activity in an erythrocyte lysis assay became evident. When pH decreased to 6.6 and 5.4, hemolytic capability of chitosan NPs increased along with the raise of concentration. Furthermore, studies with cell culture showed that these pH-responsive NPs displayed low cytotoxic effects against 3T3 fibroblasts. The influence of chitosan molecular weight, chitosan to TPP weight ratio, nanoparticle size and nature of the surfactant counterion on the membrane-disruptive properties of nanoparticles was discussed in detail. Altogether, the results achieved here showed that by inserting the lysine-based amphiphiles into chitosan NPs, pH-sensitive membranolytic and potentially endosomolytic nanocarriers were developed, which, therefore, demonstrated ideal feasibility for intracellular drug delivery.
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.
Daniele R
DR
Nogueira
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.
Laís E
LE
Scheeren
Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
M
M
Pilar Vinardell
Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
Montserrat
M
Mitjans
Departamento de Tecnología Química y de Tensioactivos, IQAC, CSIC, C/ Jordi Girona 18-26, 08034 Barcelona, Spain.
M
M
Rosa Infante
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.
Clarice M B
CM
Rolim
D065966:Absorption, Physicochemical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry*; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004058:Diffusion; D004357:Drug Synergism; D006863:Hydrogen-Ion Concentration; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D011122:Polyphosphates / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D011122:Polyphosphates; D013501:Surface-Active Agents; D048271:Chitosan; C005692:triphosphoric acid
Chitosan nanoparticles; Cytotoxicity; Hemolysis assay; Lysine-based surfactants; Membrane disruption; pH-sensitivity