OBJECTIVES: This paper describes the development and optimization of a nanoparticle delivery platform for the anticancer agent, paclitaxel, using a novel amphiphilic carrier, tetrahexyloxy-tetra-p-aminocalix[4]arene (A4C(6) ). METHODS: Nanoparticles were successfully prepared at pH4 by an emulsion evaporation method whereby an organic phase containing paclitaxel: A4C(6) (molar ratio 1:10) was dispersed by probe sonication into an aqueous phase containing 0.5% w/v polyvinyl alcohol as stabilizer. KEY FINDINGS: The drug-loaded nanoparticles had a mean size of 78.7±20.7nm, surface potential of 38.3±7.67mV, and paclitaxel loading and encapsulation efficiencies of 69.1±5.3µg drug/mg carrier and 50.4±3.2%, respectively. Transmission electron micrographs showed discrete particles with no evidence of agglomeration. In-vitro dissolution into phosphate buffered saline supplemented with 4% bovine serum albumin showed 32.7±3.9%, 82.6±5.3% and 91.0±6.0% of the encapsulated paclitaxel load was released at 5, 72 and 120h, respectively. CONCLUSIONS: This is the first report on the use of amino-substituted amphiphilic calixarenes for the encapsulation of anticancer agents. The nanoparticles produced were significantly smaller than, but had comparable drug loads to the Abraxane nanoparticles, and have the potential to achieve targeted delivery of paclitaxel to tumour tissues.
OBJECTIVES: This paper describes the development and optimization of a nanoparticle delivery platform for the anticancer agent, paclitaxel, using a novel amphiphilic carrier, tetrahexyloxy-tetra-p-aminocalix[4]arene (A4C(6) ). METHODS: Nanoparticles were successfully prepared at pH4 by an emulsion evaporation method whereby an organic phase containing paclitaxel: A4C(6) (molar ratio 1:10) was dispersed by probe sonication into an aqueous phase containing 0.5% w/v polyvinyl alcohol as stabilizer. KEY FINDINGS: The drug-loaded nanoparticles had a mean size of 78.7±20.7nm, surface potential of 38.3±7.67mV, and paclitaxel loading and encapsulation efficiencies of 69.1±5.3µg drug/mg carrier and 50.4±3.2%, respectively. Transmission electron micrographs showed discrete particles with no evidence of agglomeration. In-vitro dissolution into phosphate buffered saline supplemented with 4% bovine serum albumin showed 32.7±3.9%, 82.6±5.3% and 91.0±6.0% of the encapsulated paclitaxel load was released at 5, 72 and 120h, respectively. CONCLUSIONS: This is the first report on the use of amino-substituted amphiphilic calixarenes for the encapsulation of anticancer agents. The nanoparticles produced were significantly smaller than, but had comparable drug loads to the Abraxane nanoparticles, and have the potential to achieve targeted delivery of paclitaxel to tumour tissues.
Authors: Laura Gallego-Yerga; Inmaculada Posadas; Cristina de la Torre; Jesús Ruiz-Almansa; Francesco Sansone; Carmen Ortiz Mellet; Alessandro Casnati; José M García Fernández; Valentín Ceña Journal: Front Pharmacol Date: 2017-05-08 Impact factor: 5.810