title: Development of 2-(dimethylamino)ethyl methacrylate-based molecular recognition devices for controlled drug delivery using supercritical fluid technology.
abstract: This work reports the development of a novel potential body-friendly oral drug delivery system, which consists of a biocompatible molecularly imprinted polymer (MIP), with pH sensitive character and low cross-linking degree (20.2wt%), synthesized and processed in supercritical carbon dioxide. The MIP is synthesized using 2-(dimethylamino)ethyl methacrylate (DMAEMA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as cross-linker, and ibuprofen as molecular recognition template. The imprinted matrix was able to show a higher affinity towards ibuprofen than its corresponding non-imprinted polymer (NIP) meaning that the molecular imprinting in scCO(2) was efficient even using a low crosslinking degree. MIP showed a significant molecular recognition towards the template, presenting higher drug uptake ability in the supercritical impregnation step, loading 33.1wt% of ibuprofen compared to only 10.2wt% for the NIP polymer. In vitro drug release experiments, simulating an oral administration, showed different release profiles at pH 2.2 and pH 7.4. Zeta potential measurements were performed to both MIP and NIP showing that the imprinting process has a significant influence on the charge of the polymeric particles. Cytotoxicity assays performed with human colorectal carcinoma-derived Caco-2 cells demonstrated that the polymers are biocompatible and could be potentially used in drug delivery applications.
authors.affiliation: Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal.
authors.forename: Mara Soares
authors.initials: MS
authors.lastname: da Silva
authors.forename: Raquel
authors.initials: R
authors.lastname: Viveiros
authors.forename: Patrícia I
authors.initials: PI
authors.lastname: Morgado
authors.forename: Ana
authors.initials: A
authors.lastname: Aguiar-Ricardo
authors.forename: Ilídio J
authors.initials: IJ
authors.lastname: Correia
authors.forename: Teresa
authors.initials: T
authors.lastname: Casimiro
mesh_terms: D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D025924:Chromatography, Supercritical Fluid / Q000295:instrumentation / Q000379:methods*; D003432:Cross-Linking Reagents / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D008689:Methacrylates / Q000008:administration & dosage / Q000737:chemistry*; D054802:Molecular Imprinting / Q000379:methods*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D013499:Surface Properties
chemical_list: D003432:Cross-Linking Reagents; D008689:Methacrylates; D011108:Polymers; C004919:ethylene dimethacrylate; C049840:2-(dimethylamino)ethyl methacrylate; D007052:Ibuprofen