Binding and release of drugs into and from thermosensitive poly(N-vinyl caprolactam) nanoparticles.
Three model drug substances, the beta-blocking agents nadolol and propranolol and a choline-esterase inhibitor tacrine, were used in order to determine how different drug molecules affect the behavior of thermally responsive polymer nanoparticles composed of poly(N-vinylcaprolactam) (PVCL). Pure PVCL particles in water exist in a swollen state at room temperature, but the size of the particles decreases discontinuously when the temperature is raised above the volume phase transition temperature. At temperatures above this transition temperature, water is expelled out from the nanoscopic hydrogel particles. Light scattering studies revealed that the more hydrophobic drug substances, propranolol and tacrine, considerably swell the PVCL-microgel. The more hydrophilic drug, nadolol, decreased the transition temperature of PVCL particles, whereas the transition temperature values of pure PVCL particles and that of the added propranolol and tacrine were quite similar. Attenuated drug release results showed that the beta-blocking agents were tightly bound to the microgel, and this was more evident at higher temperatures. On the contrary, the release of tacrine across the cellulose membrane was increased when PVCL particles were present. Thus, both physical and chemical properties of the drugs clearly affected their binding to PVCL particles and the release of drugs was affected by the temperature.
Division of Pharmaceutical Technology, Viikki Drug Discovery Technology Center, University of Helsinki, PB 56, FIN-00014, Helsinki, Finland.
Henna
H
Vihola
Antti
A
Laukkanen
Jouni
J
Hirvonen
Heikki
H
Tenhu
D000319:Adrenergic beta-Antagonists / Q000737:chemistry; D002209:Caprolactam / Q000031:analogs & derivatives* / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002800:Cholinesterase Inhibitors / Q000737:chemistry; D020100:Hydrogels; D007700:Kinetics; D008027:Light; D009248:Nadolol / Q000737:chemistry*; D036103:Nanotechnology; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011433:Propranolol / Q000737:chemistry*; D012542:Scattering, Radiation; D013619:Tacrine / Q000737:chemistry*; D013696:Temperature; D014867:Water
D000319:Adrenergic beta-Antagonists; D002800:Cholinesterase Inhibitors; D020100:Hydrogels; D011108:Polymers; D014867:Water; C086861:poly-N-vinylcaprolactam; D009248:Nadolol; D013619:Tacrine; D002209:Caprolactam; D011433:Propranolol