ABSTRACT
Molecularly imprinted hydrogel nanospheres as devices for the controlled/sustained release of 5-fluororacil in biological fluids were synthesized employing one-pot precipitation technique as the polymerization method. Methacrylic acid as a functional monomer and ethylene glycole dimethacrylate as a cross-linker were used in polymeric feed. Morphological and hydrophilic properties were determined by scanning electron microscopy and water content measurement, and recognition and selectivity properties of spherical molecularly imprinted polymers were compared with the spherical non-imprinted polymers, both in organic (acetonitrile) and water media. Finally, in vitro release studies were performed in plasma simulating fluids.
Subject(s)
Antimetabolites, Antineoplastic/chemical synthesis , Drug Delivery Systems/methods , Fluorouracil/chemical synthesis , Molecular Imprinting/methods , Nanospheres/chemistry , Acetonitriles/chemistry , Cross-Linking Reagents/chemistry , Delayed-Action Preparations/chemical synthesis , Ethylene Glycol/chemistry , Hydrogel, Polyethylene Glycol Dimethacrylate/chemistry , Methacrylates/chemistry , Microscopy, Electron, Scanning , Molecular Structure , Nanoparticles/chemistry , Nanotechnology/methods , Polymers/chemical synthesis , Technology, Pharmaceutical , Uracil/chemical synthesis , Water/analysisABSTRACT
Ferulic acid plays a chemopreventive role in cancer by inducing tumor cells apoptosis. As mitochondria play a key role in the induction of apoptosis in many cells types, here we investigate the mitochondrial permeability transition (MPT) and the release of cytochrome c induced by ferulic acid and its esters in rat testes mitochondria, in TM-3 and MLTC-1 cells. While ferulic acid, but not its esters, induced MPT and cytochrome c release in rat testes isolated mitochondria, in TM-3 cells we found that both ferulic acid and its esters induced cytochrome c release from mitochondria in a dose-dependent manner, suggesting a potential target of these compounds in the induction of cell apoptosis. The apoptosis induced by ferulic acid is therefore associated with the mitochondrial pathway involving cytochrome c release and caspase-3 activation.
Subject(s)
Apoptosis/drug effects , Caspase 3/metabolism , Coumaric Acids/pharmacology , Cytochromes c/metabolism , Mitochondria/enzymology , Testis/enzymology , Animals , Cell Line , Coumaric Acids/chemical synthesis , Enzyme Activation/drug effects , Esters/chemical synthesis , Esters/pharmacology , Male , RatsABSTRACT
A new sorbent for molecularly imprinted solid phase extraction (MISPE) was synthesized to extract and purify alpha-tocopherol (alpha-TP) from vegetable sources. Molecularly imprinted polymers (MIP) were synthesized using methacrylic acid (MAA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent using a photo-polymerization procedure. A thermo-polymerization was also performed but no imprinting effect in the resulting materials was raised. The proposed MISPE protocol could overcome the drawback of traditional detection methods, which require pre-treatments of the samples. The possibility to obtain the selective recognition of alpha-TP from natural samples in aqueous mixtures represents one of the main advantages of our materials. Our procedure involves the direct HPLC injection of eluate without any treatment and above all the use of no toxic and biocompatible organic solvents. After the evaluation of the selectivity of the alpha-TP imprinted polymers, the performance of these materials as solid phase extraction (SPE) sorbents was investigated. Our MISPE-HPLC procedure has a high sensitivity, LOD and LOQ were 3.49x10(-7) and 1.16x10(-6) mol L(-1), respectively, as well as good precision (intraday precision below 3.3% and interday precisions below 6.5%) and recovery (60%). Thus, it can be successfully used for the purification of alpha-TP from bay leaves.
Subject(s)
Laurus , Solid Phase Extraction/methods , alpha-Tocopherol/isolation & purification , Chromatography, High Pressure Liquid/methods , Laurus/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Leaves/chemistry , alpha-Tocopherol/chemistryABSTRACT
The aim of this research is the preparation of acryloylated bovine serum albumin microspheres and the evaluation of their employment in drug delivery. The influence of preparation parameters on albumin microspheres and the chemicophysical properties of loaded drugs were investigated. In particular, we focused our attention on acylation albumin degree, amount of acryloylated albumin against comonomer in the polymerization step, and finally the release profile. We considered on the interaction drug-matrix, the fuctionalization degree of albumin, and the water affinity of matrix.
Subject(s)
Drug Delivery Systems/methods , Microspheres , Pharmaceutical Preparations/administration & dosage , Serum Albumin/chemistry , Acrylates/chemistry , Adrenergic beta-Antagonists/administration & dosage , Adrenergic beta-Antagonists/chemistry , Adrenergic beta-Antagonists/pharmacokinetics , Ammonium Sulfate/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Azasteroids/chemistry , Cattle , Cross-Linking Reagents/chemistry , Diflunisal/administration & dosage , Diflunisal/chemistry , Diflunisal/pharmacokinetics , Dihydrotestosterone/analogs & derivatives , Dihydrotestosterone/chemistry , Drug Stability , Fluorouracil/administration & dosage , Fluorouracil/chemistry , Fluorouracil/pharmacokinetics , Hydrogen-Ion Concentration , Microscopy, Electron, Scanning , Organometallic Compounds/chemistry , Particle Size , Pharmaceutical Preparations/chemistry , Pharmaceutical Preparations/metabolism , Propranolol/administration & dosage , Propranolol/chemistry , Propranolol/pharmacokineticsABSTRACT
This article reports on the preparation of acryloylated bovine serum albumin microspheres and the evaluation of their employment in drug delivery areas. The influence of preparation parameters on albumin microspheres and the chemicophysical properties of loaded drugs were investigated. In particular, we focussed on acylation albumin degree and the amount of acryloylated albumin against comonomer in the polymerization step. Finally the release profile took into consideration the interaction drug-matrix, the fuctionalization degree of albumin, and the water affinity of matrix.
Subject(s)
Drug Delivery Systems/methods , Microspheres , Pharmaceutical Preparations/administration & dosage , Serum Albumin, Bovine/chemistry , Adrenergic beta-Antagonists/administration & dosage , Adrenergic beta-Antagonists/chemistry , Adrenergic beta-Antagonists/pharmacokinetics , Animals , Cattle , Cross-Linking Reagents/chemistry , Fluorouracil/administration & dosage , Fluorouracil/chemistry , Fluorouracil/pharmacokinetics , Hydrogen-Ion Concentration , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/pharmacokinetics , Microscopy, Electron, Scanning , Pharmaceutical Preparations/chemistry , Propranolol/administration & dosage , Propranolol/chemistry , Propranolol/pharmacokinetics , Technology, Pharmaceutical/methods , Time FactorsABSTRACT
Spherical molecularly imprinted polymers (SMIPs) have been prepared via a novel precipitation polymerization using sulfasalazine (prodrug used in the diseases of the colon) as template. The sulfasalazine was incorporated into SMIPs and into a spherical non-imprinted polymer (control), and then the release rate of the bioactive agent at different pH values was evaluated. Considerable differences in the release characteristics between imprinted and non-imprinted polymers have been observed. This opens the possibility of the development of drug release systems capable of modulating the release of a specific molecule. Photomicrography of spherical molecularly imprinted polymers (SMIPs).
Subject(s)
Anti-Infective Agents/chemistry , Methacrylates/chemistry , Nitriles/chemistry , Polymers/chemical synthesis , Sulfasalazine/chemistry , Anti-Infective Agents/administration & dosage , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemical synthesis , Delayed-Action Preparations/chemistry , Drug Delivery Systems , Microspheres , Polymers/chemistry , Sulfasalazine/administration & dosage , Technology, PharmaceuticalABSTRACT
Spherical pH-sensitive microparticles have been prepared by reverse phase suspension polymerization technique. Starting polymer has been alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) partially derivatized with glycidylmethacrylate (GMA). PHEA-GMA copolymer (PHG) has been crosslinked in the presence of acrylic acid (AA) or methacrylic acid (MA) at various concentration. The obtained microparticles have been characterized by FT-IR spectrophotometry, particle size distribution analysis and scanning electron microscopy. In order to have information about water affinity of the prepared samples, swelling measurements have been carried out in aqueous media which simulate some biological fluids. The possibility to employ the prepared samples as pH-sensitive microparticles has been investigated by performing in vitro release studies. Experimental data have showed that the release rate from these microparticles depends on the environmental pH and the chemical structure of the drug.
