RESUMO
Novel drug-conjugated amphiphilic A(14)B(7) miktoarm star copolymers composed of 14 poly(epsilon-caprolactone) (PCL) arms and 7 poly(ethylene glycol) (PEG) arms with beta-cyclodextrin (beta-CD) as core moiety were synthesized by the combination of controlled ring-opening polymerization (CROP) and "click" chemistry. (1)H NMR, FT-IR, and SEC-MALLS analyses confirmed the well-defined A(14)B(7) miktoarm star architecture. These amphiphilic miktoarm star copolymers could self-assemble into multimorphological aggregates in aqueous solution, which were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Moreover, the drug-loading efficiency and drug-encapsulation efficiency of the drug-conjugated miktoarm star copolymers were higher than those of the corresponding non-drug-conjugated miktoarm star copolymers.
Assuntos
Poliésteres/química , Polietilenoglicóis/química , Polímeros/química , Polímeros/síntese química , beta-Ciclodextrinas/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Cromatografia em Gel , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Ibuprofeno/química , Ibuprofeno/metabolismo , Espectroscopia de Ressonância Magnética , Teste de Materiais , Microscopia Eletrônica de Transmissão , Nanopartículas , Polímeros/metabolismo , Espectrometria de Massas por Ionização por Electrospray , beta-Ciclodextrinas/metabolismoRESUMO
Two trace impurities in the bulk drug lisinopril were detected by means of high-performance liquid chromatography coupled with mass spectrometry (HPLC/MS) with a simple and sensitive method suitable for HPLC/MSn analysis. The fragmentation behavior of lisinopril and the impurities was investigated, and two unknown impurities were elucidated as 2-(6-amino-1-(1-carboxyethylamino)-1-oxohexan-2-ylamino)-4-phenylbutanoic acid and 6-amino-2-(1-carboxy-3-phenylpro-pylamino)-hexanoic acid on the basis of the multi-stage mass spectrometry and exact mass evidence. The proposed structures of the two unknown impurities were further confirmed by nuclear magnetic resonance (NMR) experiments after preparative isolation.