Conducting polymer nanoparticles for a voltage-controlled release of pharmacological chaperones. Issue 12 (25th February 2021)

• Record Type: Journal Article
• Authors: Enshaei, Hamidreza; Puiggalí-Jou, Anna; Saperas, Núria; Alemán, Carlos
• Is Part Of: Soft matter. Volume 17:Issue 12(2021)
• Page Start: 3314
• Page End: 3321
• Publication Date: 2021-02-25
• Subjects: Soft condensed matter -- Periodicals; 530.413
• DOI: 10.1039/d1sm00036e
• Languages: English
• ISSNs: 1744-683X

Abstract

Abstract : Sustained electrical stimuli on conducting polymer nanoparticles allow the controlled release of loaded pharmacological chaperones, which are low-molecular weight chemical molecules used for the treatment of diseases caused by protein instability. Abstract : Pharmacological chaperones (PCs) are low-molecular weight chemical molecules used in patients for the treatment of some rare diseases caused primarily by protein instability. A controlled and on-demand release of PCs via nanoparticles is an alternative for cases in which long treatments are needed and prolonged oral administration could have adverse effects. In this work, pyrimethamine (PYR), which is a potent PC consisting of pyrimidine-2, 4-diamine substituted at position 5 by a p -chlorophenyl group and at position 6 by an ethyl group, was successfully loaded in electroresponsive poly(3, 4-ethylenedioxythiophene) nanoparticles (PEDOT NPs). The PYR-loading capacity was 11.4 ± 1.5%, with both loaded and unloaded PEDOT NPs exhibiting similar sizes (215 ± 3 and 203 ± 1 nm, respectively) and net surface charges (−26 ± 7 and −29 ± 6 mV, respectively). In the absence of electrical stimulus, the release of PC from loaded NPs is very low (1.6% in 24 h and 18% in 80 days) in aqueous environments. Instead, electrical stimuli that sustained for 30 min enhanced the release of PYR, which was ∼50% when the voltage was scanned from –0.5 V to 0.5 V (cyclic voltammetry) and ∼35% when a constant voltage of 1.0 V was applied (chronoamperometry).