Conducting polymer nanoparticles for voltage-controlled release of pharmacological chaperones

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 a...

Descripción completa

Detalles Bibliográficos
Autores: Enshaei, Hamidreza, Puiggalí Jou, Anna|||0000-0002-2234-9436, Saperas Plana, Núria|||0000-0002-5419-7502, Alemán Llansó, Carlos|||0000-0003-4462-6075
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/343511
Acceso en línea:https://hdl.handle.net/2117/343511
https://dx.doi.org/10.1039/D1SM00036E
Access Level:acceso abierto
Palabra clave:Conducting polymers
Polímers conductors
Àrees temàtiques de la UPC::Enginyeria química
Descripción
Sumario: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).