Development of a pH-responsive drug delivery system for enantioselective-controlled delivery of racemic drugs.
This study aimed to develop enantioselective-controlled drug delivery systems for selective release of the required (S)-enantiomer in a dose formulation containing a racemic drug in response to pH stimuli. The recognition system was obtained from a nanoparticle-on-microsphere (NOM) molecularly imprinted polymer (MIP) with a multifunctional chiral cinchona anchor synthesised by suspension polymerisation using ethylene glycol dimethacrylate as a cross-linker. (S)-omeprazole was used as an imprinting molecule conferring stereoselectivity upon the polymers. The ability of the prepared recognition polymers to selectively rebind (S)-omeprazole was evident at different pH levels (the highest being at pH 7.4). The partial selective-release phenomenon of the (S)-enantiomer in MIP-containing composite cellulose membranes with increased vehicular racemic omeprazole concentrations was highly pH-dependent. Cinchona-bonded polymers imprinted with (S)-omeprazole could recognise the moldable contact site of (S)-omeprazole independently of its chirality; this is responsible for the delivery of (S)-enantiomer from racemic omeprazole. The controlled-release drug devices were fabricated with synthesised composite latex, and consisted of a pH stimuli-responsive poly(hydroxyethyl methacrylate) (HEMA) and polycaprolactone-triol (PCL-T) blend, and a MIP with preloaded drug, along with pH 7.4 buffer in the device's interior. The results demonstrate that drug delivery systems containing (S)-omeprazole imprinted cinchona-polymer nanoparticle-on-microspheres may maximise efficacy while minimising dose frequency.
Suedee
Roongnapa
R
Molecular Recognition Materials Research Unit, Drug Delivery System Excellence Center, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hatyai, Songkla 90112, Thailand. roongnapa.s@psu.ac.th
Jantarat
Chutima
C
Lindner
Wolfgang
W
Viernstein
Helmut
H
Songkro
Sarunyoo
S
Srichana
Teerapol
T
D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D002482:Cellulose / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D008567:Membranes, Artificial; D008689:Methacrylates / Q000737:chemistry; D008863:Microspheres; D054802:Molecular Imprinting; D053758:Nanoparticles / Q000737:chemistry*; D009853:Omeprazole / Q000008:administration & dosage*; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013237:Stereoisomerism
D000897:Anti-Ulcer Agents; D008567:Membranes, Artificial; D008689:Methacrylates; D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone; C005044:hydroxyethyl methacrylate; D002482:Cellulose; D009853:Omeprazole