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.
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
Roongnapa
R
Suedee
Chutima
C
Jantarat
Wolfgang
W
Lindner
Helmut
H
Viernstein
Sarunyoo
S
Songkro
Teerapol
T
Srichana
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