ABSTRACT
A convenient and environmentally friendly method of fabricating glucose biosensors is proposed. Glucose oxidase (GOD) was immobilized on electrochemically reduced graphene oxide (ERGO) which was adsorbed on the poly-L-lysine (PLL) modified glassy carbon electrode after being immersed in GO solution for 4 h. The electrochemical behaviors of GOD/ERGO/PLL/GC electrode have been investigated by cyclic voltammetry. Direct electron transfer between GOD immobilized with ERGO/PLL and GC electrode was observed. Moreover, the GOD/ERGO/PLL/GC electrode exhibited excellent electrocatalytic activity for the detection of glucose with a linear range from 0.25 to 5 mmol L(-1).
Subject(s)
Biosensing Techniques/methods , Carbon/chemistry , Glucose/analysis , Glucose/chemistry , Graphite/chemistry , Oxides/chemistry , Polylysine/chemistry , Electrochemistry , Electrodes , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Glass/chemistry , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Oxidation-ReductionABSTRACT
PURPOSE: Fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] is a cytotoxic retinoid that suffers from a wide interpatient variation in bioavailability when delivered orally in a corn oil capsule. The poor bioavailability of the capsule formulation may have limited responses in clinical trials, and the large capsules are not suitable for young children. To support the hypothesis that a novel organized lipid matrix, LYM-X-SORB, can increase the oral bioavailability of fenretinide, fenretinide in LYM-X-SORB matrix and in a powderized LYM-X-SORB formulation was delivered to mice. EXPERIMENTAL DESIGN: Fenretinide was delivered orally to mice as the contents of the corn oil capsule, in LYM-X-SORB matrix (4-HPR/LYM-X-SORB matrix) or in a LYM-X-SORB matrix powderized with sugar and flour (4-HPR/LYM-X-SORB oral powder). Levels of 4-HPR, and its principal metabolite, N-(4-methoxyphenyl)retinamide, were assayed in plasma and tissues. RESULTS: In a dose-responsive manner, from 120 to 360 mg/kg/d, delivery to mice of 4-HPR in LYM-X-SORB matrix, or as 4-HPR/LYM-X-SORB oral powder, increased 4-HPR plasma levels up to 4-fold (P<0.01) and increased tissue levels up to 7-fold (P<0.01) compared with similar doses of 4-HPR delivered using capsule contents. Metabolite [N-(4-methoxyphenyl)retinamide] levels mirrored 4-HPR levels. Two human neuroblastoma murine xenograft models showed increased survival (P<0.03), when treated with 4-HPR/LYM-X-SORB oral powder, confirming the bioactivity of the formulation. CONCLUSIONS: 4-HPR/LYM-X-SORB oral powder is a novel, oral drug delivery formulation, suitable for pediatric use, which warrants further development for the delivery of fenretinide in the treatment of cancer. A phase I clinical trial in pediatric neuroblastoma is in progress.
Subject(s)
Antineoplastic Agents/administration & dosage , Fatty Acids/chemistry , Fenretinide/administration & dosage , Lysophosphatidylcholines/chemistry , Monoglycerides/chemistry , Neuroblastoma/drug therapy , Peripheral Nervous System Neoplasms/drug therapy , Administration, Oral , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Biological Availability , Cell Line, Tumor , Drug Delivery Systems , Fenretinide/chemistry , Fenretinide/pharmacokinetics , Humans , Mice , Powders , Tissue DistributionABSTRACT
A high-performance liquid chromatography (HPLC) method was developed to measure levels of d-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (d-threo-PPMP) in mouse plasma and liver. d-threo-PPMP was measured by HPLC with a Luna Pheny-Hexyl column (5 microm, 250 mm x 4.6 mm) employing UV detection at 210 nm using a mobile phase of potassium phosphate buffer (20mM, pH 3.0)-acetonitrile in a 45:55 (v/v) ratio. d-threo-1-phenyl-2-pentadecanoylamino-3-morpholino-1-propanol (PC15MP) was employed as an internal standard (IS). The lower limit of quantitation (LLOQ) was 0.3 microg/ml. The assay was linear over a concentration range of 0.3-10 microg/ml, with acceptable precision and accuracy. Assayed in plasma, the intra- and inter-day validation for all coefficients of variation (R.S.D.%) were found less than 15%. The method was applied to samples from athymic (nu/nu) mice treated with d-threo-PPMP by intraperitoneal injection. d-threo-PPMP levels of approximately 10-20 microg/ml ( approximately 20-40 microM) in plasma and approximately 45 microg/g in liver were obtained. The present method can be used to quantify d-threo-PPMP in mice for bioavailability and dose-response studies.
