pH-sensitive nanoparticles for improved oral delivery of dapsone: risk assessment, design, optimization and characterization

• Published in: Nanomedicine (London, England) Vol. 12; no. 16; pp. 1975 - 1990
• Main Authors: Chaves, Luíse L, Costa Lima, Sofia A, Vieira, Alexandre CC, Barreiros, Luísa, Segundo, Marcela A, Ferreira, Domingos, Sarmento, Bruno, Reis, Salette
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.08.2017
• Subjects: Acids; Administration, Oral; Bioavailability; Box-Behnken design; Caco-2 cell; Cell Line, Tumor; Cell Survival - drug effects; Dapsone - administration & dosage; Dapsone - pharmacology; Dapsone - toxicity; Drug Carriers - chemistry; Drug delivery systems; Drug Liberation; Drugs; Ethanol; Eudragit; Humans; Hydrogen-Ion Concentration; L100; Leprostatic Agents - administration & dosage; Leprostatic Agents - pharmacology; Leprostatic Agents - toxicity; Leprosy; Microemulsions; Nanoparticles; Nanoparticles - chemistry; Optimization; Particle Size; Permeability; Pharmaceuticals; Plackett-Burman design; Polymers; Polyvinyl alcohol; release assay; Spectroscopy, Fourier Transform Infrared - methods; Surface Properties; Surfactants; United States > US; Portugal; Germany; leprosy; Plackett–Burman design; Box-Behnken design; in vitro release assay; Caco-2 cell; Eudragit® L100
• ISSN: 1743-5889; 1748-6963
• DOI: 10.2217/nnm-2017-0105

To optimize the production of pH-sensitive dapsone (DAP) nanoparticles based on Eugradit L100 (NPs-EL100-DAP) for oral delivery. NPs-EL100-DAP were optimized using a Plackett-Burman design and a Box-Behnken design. The physicochemical properties of the obtained nanoparticles were monitored by microscopy, dynamic light scattering, Fourier transform infrared spectroscopy, differential scanning calorimetry, release assays, and examined for cytotoxicity and permeation across intestinal barrier. The release assay of NPs-EL100-DAP confirmed the nanoparticles' pH sensitivity and the ability to deliver DAP at intestinal environment. NPs-EL100-DAP demonstrated enhanced intestinal interactions in comparison to free DAP, across Caco-2 monolayers. These studies demonstrate the potential of NPs-EL100-DAP as a therapeutic platform for oral treatment of leprosy.