Compatibility of calcium chloride with milrinone, epinephrine, vasopressin, and heparin via in vitro testing and simulated Y-site administration.

PURPOSE: The purpose of this study is to evaluate calcium chloride (CaCl) compatibility with commercially available and extemporaneously compounded milrinone, vasopressin, epinephrine, and heparin. This report describes 2 clinical scenarios in which patients experienced intravenous catheter precipitation when receiving multiple continuous infusions, including CaCl, and the results of an in vitro simulation of those scenarios. The hypothesis was that one or a combination of the medications would precipitate with CaCl. METHODS: CaCl compatibility was tested in 3 stages to simulate clinical situations where line precipitation occurred. Multiple tests were conducted in each stage to determine if precipitation had occurred, including visual assessment, absorbance measurement at 650 nm, and pH measurement. First, milrinone, vasopressin, epinephrine, and heparin were mixed pairwise with CaCl in a test tube. Second, the medications were mixed in different combinations deemed likely to precipitate. Finally, 5 medications were infused via simulated Y-site administration. Incompatibility was defined as observed crystals, haziness, or turbidity upon visual inspection or absorbance of greater than 0.01 absorbance unit (AU). All solutions were tested at time 0 and at 20, 60, 240, and 1,440 minutes. RESULTS: Across all tests, only a commercially available formulation of heparin 2 units/mL in 0.9% sodium chloride injection precipitated with CaCl, alone or in combination with other medications. Upon further review, it was found that this specific formulation of heparin contained a monohydrate and dibasic sodium phosphate buffer. CONCLUSION: CaCl only precipitated with a commercially available heparin formulation that contained a phosphate buffer. CaCl was deemed to be compatible with all other medications and formulations tested.

Alternating magnetic field-induced hyperthermia increases iron oxide nanoparticle cell association/uptake and flux in blood-brain barrier models.

PURPOSE: Superparamagnetic iron oxide nanoparticles (IONPs) are being investigated for brain cancer therapy because alternating magnetic field (AMF) activates them to produce hyperthermia. For central nervous system applications, brain entry of diagnostic and therapeutic agents is usually essential. We hypothesized that AMF-induced hyperthermia significantly increases IONP blood-brain barrier (BBB) association/uptake and flux. METHODS: Cross-linked nanoassemblies loaded with IONPs (CNA-IONPs) and conventional citrate-coated IONPs (citrate-IONPs) were synthesized and characterized in house. CNA-IONP and citrate-IONP BBB cell association/uptake and flux were studied using two BBB Transwell(®) models (bEnd.3 and MDCKII cells) after conventional and AMF-induced hyperthermia exposure. RESULTS: AMF-induced hyperthermia for 0.5 h did not alter CNA-IONP size but accelerated citrate-IONP agglomeration. AMF-induced hyperthermia for 0.5 h enhanced CNA-IONP and citrate-IONP BBB cell association/uptake. It also enhanced the flux of CNA-IONPs across the two in vitro BBB models compared to conventional hyperthermia and normothermia, in the absence of cell death. Citrate-IONP flux was not observed under these conditions. AMF-induced hyperthermia also significantly enhanced paracellular pathway flux. The mechanism appears to involve more than the increased temperature surrounding the CNA-IONPs. CONCLUSIONS: Hyperthermia induced by AMF activation of CNA-IONPs has potential to increase the BBB permeability of therapeutics for the diagnosis and therapy of various brain diseases.

Synthesis and characterization of PEG-iron oxide core-shell composite nanoparticles for thermal therapy.

In this study, core-shell nanoparticles were developed to achieve thermal therapy that can ablate cancer cells in a remotely controlled manner. The core-shell nanoparticles were prepared using atomic transfer radical polymerization (ATRP) to coat iron oxide (Fe3O4) nanoparticles with a poly(ethylene glycol) (PEG) based polymer shell. The iron oxide core allows for the remote heating of the particles in an alternating magnetic field (AMF). The coating of iron oxide with PEG was verified through Fourier transform infrared spectroscopy and thermal gravimetric analysis. A thermoablation (55°C) study was performed on A549 lung carcinoma cells exposed to nanoparticles and over a 10 min AMF exposure. The successful thermoablation of A549 demonstrates the potential use of polymer coated particles for thermal therapy.

Intelligent biosynthetic nanobiomaterials for hyperthermic combination chemotherapy and thermal drug targeting of HSP90 inhibitor geldanamycin.

An intelligent biosynthetic nanobiomaterial (IBN) platform was explored for drug delivery applications for hyperthermic combination chemotherapy and thermal drug targeting. Geldanamycin (GA), a heat shock protein 90 inhibitor, was conjugated to novel thermosensitive poly(K)(8)-poly(VPGXG)(60) block copolymers [K(8)-ELP(1-60)] with guest residues as valine, alanine and glycine in a 5:2:3 ratio at the 'X' position. The conjugates were completely soluble in PBS and showed a characteristic thermosensitive inverse phase transition. [K(8)-ELP(1-60)]-GA conjugate nanoparticles showed a size ranging from 50 to 200 nm depending upon temperature. Relevant to systemic drug delivery in vivo, these IBNs stably disperse in aqueous solution. Cytotoxicity assays have shown that the IBN from [K(8)-ELP(1-60)]-GA conjugates exhibits effective hyperthermic combination chemotherapy with facile heat modulation.