Development of Tolerance to Chronic Intermittent Furosemide Therapy in Pediatric Patients.

OBJECTIVES: The purpose of this study is to describe whether tolerance develops in pediatric patients receiving chronic intermittent furosemide therapy, to characterize when it occurs and whether age-related variations exist. The effects of increasing total daily dose of furosemide and concurrent diuretics and vasopressors were assessed as secondary aims. METHODS: Charts from patients receiving intravenous or oral furosemide for at least 3 consecutive days of therapy between June 1, 2013, and December 31, 2013, were reviewed retrospectively. Daily net fluid balance was used as the objective marker for development of tolerance. Net fluid balance (mL/kg/mg) was defined as the difference in a patient's daily intake and urine output (mL), normalized by weight (kg) and total daily dose of furosemide (mg). RESULTS: Sixty-one patients, aged 2 days to 20 years (median 3 years), were included in this study. Median daily dose of furosemide was 1.96 mg/kg/day (range, 0-13.7 mg/kg/day). Average net fluid balance for all patients on the first day and last day of therapy was 6.83 and 26.66 mL/kg/mg, respectively (p = 0.011). Linear regression and Spearman's correlation found no significant relationship between age and difference in net fluid balance between the first and last day. Linear mixed-effects model for net fluid balance with day as covariate found that net fluid balance increases over time (p = 0.002). CONCLUSIONS: Pediatric patients appear to develop tolerance to chronic intermittent furosemide therapy.

Nanotechnology applications in cancer.

Cancer nanotechnology is an interdisciplinary area of research in science, engineering, and medicine with broad applications for molecular imaging, molecular diagnosis, and targeted therapy. The basic rationale is that nanometer-sized particles, such as semiconductor quantum dots and iron oxide nanocrystals, have optical, magnetic, or structural properties that are not available from molecules or bulk solids. When linked with tumor targeting ligands such as monoclonal antibodies, peptides, or small molecules, these nanoparticles can be used to target tumor antigens (biomarkers) as well as tumor vasculatures with high affinity and specificity. In the mesoscopic size range of 5-100 nm diameter, nanoparticles also have large surface areas and functional groups for conjugating to multiple diagnostic (e.g., optical, radioisotopic, or magnetic) and therapeutic (e.g., anticancer) agents. Recent advances have led to bioaffinity nanoparticle probes for molecular and cellular imaging, targeted nanoparticle drugs for cancer therapy, and integrated nanodevices for early cancer detection and screening. These developments raise exciting opportunities for personalized oncology in which genetic and protein biomarkers are used to diagnose and treat cancer based on the molecular profiles of individual patients.

Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery.

Nanotechnology refers to the interactions of cellular and molecular components and engineered materials-typically, clusters of atoms, molecules, and molecular fragments into incredibly small particles-between 1 and 100 nm. Nanometer-sized particles have novel optical, electronic, and structural properties that are not available either in individual molecules or bulk solids. The concept of nanoscale devices has led to the development of biodegradable self-assembled nanoparticles, which are being engineered for the targeted delivery of anticancer drugs and imaging contrast agents. Nanoconstructs such as these should serve as customizable, targeted drug delivery vehicles capable of ferrying large doses of chemotherapeutic agents or therapeutic genes into malignant cells while sparing healthy cells. Such "smart" multifunctional nanodevices hold out the possibility of radically changing the practice of oncology, allowing easy detection and then followed by effective targeted therapeutics at the earliest stages of the disease. In this article, we briefly discuss the use of bioconjugated nanoparticles for the delivery and targeting of anticancer drugs.

Poly(D,L-lactide-co-ethyl ethylene phosphate)s as new drug carriers.

Many biodegradable polymers have been developed for controlled drug delivery. The plethora of drug therapies and types of drugs demand different formulations, fabrications conditions and release kinetics. No one single polymer can satisfy all the requirements. To extend the properties of poly(D,L-lactide) (PLA), we synthesized copolymers of PLA and poly(ethylethylene phosphate) (PEEP) by ring-opening polymerization using Al(Oipr)3 as the initiator. The copolymers were structurally characterized by IR and 1H NMR. DSC data confirmed the formation of random microphase structure in all the copolymers, and showed a decrease of Tg from 43.2 to -22.6 degrees C when the molar content of ethylethylene phosphate (EEP) increased from 5 to 40%. The hydrophilicity of the copolymers increased with EEP content. In contrast to the degradation behavior of PLA, disc samples made of PLAEEP90 showed a linear weight loss profile in PBS (pH 7.4) at 37 degrees C. BSA microspheres using PLAEEP90 were prepared by double-emulsion method, yielding a loading level of 4.3% and a loading efficiency of 75%. The BSA release profile consisted of an initial burst (9%) on the first day, followed by a daily 4% release for the following 40 days, resulting in 91% of the BSA release in a near linear manner. The released BSA remained intact according to SDS-PAGE data. Cytotoxicity and histopathology studies showed low toxicity in HeLa cells and good tissue biocompatibility in mouse brain, respectively. PLAEEP is a promising biodegradable polymer for controlled drug delivery.