Effect of pharmaceuticals on thermoreversible gelation of PEO-PPO-PEO copolymers

Pluronic F127, a triblock copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), has generated considerable interest as a drug delivery vehicle due to its ability to gel at physiological temperatures. This work examines the gelation behavior of Pluronic F127 in the presence of a series of hydrophobic pharmaceuticals, to determine whether there is any correlation between gelation and physicochemical parameters of drug solutes. The study includes the local anesthetics dibucaine, lidocaine, and tetracaine; the pharmaceutical additives methyl paraben, ethyl paraben, and propyl paraben; the anti-cancer agents paclitaxel and baccatin III; and the anti-inflammatory agent sulindac. The results indicate that the presence of local anesthetics and pharmaceutical additives allows F127 solutions to form gels at lower copolymer concentrations; local anesthetics and pharmaceutical additives also shift gelation down to a lower gelation temperature. This behavior is strongly dependent on drug solubility; poorly soluble drugs (paclitaxel, baccatin III, sulindac) do not change the lower gelation temperature or minimum F127 concentration for gelation. An equation relating the decrease in gelation temperature to drug solubility is presented, and the equation fits the data well. The results have significant positive implications on the toxicity and economic issues related to use of Pluronic F127 in drug delivery.     

Operator algebras and a theorem of Dieudonne

LetA be aC*-algebra with second dualA″. Let (φ _n)(n=1,...) be a sequence in the dual ofA such that limφ _n(a) exists for eacha εA. In general, this does not imply that limφ _n(x) exists for eachx εA″. But if limφ _n(p) exists whenever p is the range projection of a positive self-adjoint element of the unit ball ofA, then it is shown that limφ _n(x) does exist for eachx inA″. This is a non-commutative generalisation of a celebrated theorem of Dieudonné. A new proof of Dieudonné’s theorem, for positive measures, is given here. The proof of the main result makes use of Dieudonné’s original theorem.     

New Aqueous Gel Based on Soluble Cyclodextrin/Vitamin A Inclusion Complex

Rameb (randomized dimethyl--cyclodextrin) was mixed with vitamin A propionate (PVA) (molar ratio 10/1 in water) and a water soluble complex was formed and studied by HPLC and NMR (structure, concentration and stability of PVA). Then solution was used to form an aqueous gel. The skin absorption of PVA through stratum corneum, epidermis and dermis of human skin (on modified Franz cells) was assayed by HPLC and was compared to that of a reference gel (or oil) without cyclodextrin. The solution obtained contains a maximum of 10 mg/mL PVA (if saturated with Rameb) and the PVA can remain stable up to 90 days in solution, and up to 1 year if freeze-dried (storage at 4 °C, in the dark). The results of the different experiments of skin distribution were statistically analyzed and show that when complexed with Rameb, the amount of PVA that penetrates each skin layer is significantly higher than pure PVA. The results also show that PVA cannot pass through the dermis and enter the circulation.     

Crystallization of polydioxolan. III. Microscopy and dilatometric analysis of the crystallization kinetics

Crystallization kinetics has been studied for a polydioxolan (PDOL) sample, over a wide temperature range, by dilatometry and microscopy. The dilatometry results can be analyzed using the Avrami equation. At temperatures higher than 22°C, the crystallization data must be analyzed in two steps: the first part of the curve corresponds to PDOL with a very disordered morphology (Phase I) while the second part of the crystallization curve is related to a spherulitic morphology (Phase II). The passage from the low to the high crystallization temperature region is associated with a change in the Avrami exponent from 3 to 4. The crystal surface free-energy product σσ_e was found to be 18 × 10² erg²/cm⁴, very close to that of polyoxymethylene. The crystallization kinetics was studied by microscopy over the temperature range?18 to 35°C. Growth and nucleation rates were recorded. Two phases are found only at temperatures higher than 22°C. The appearance of Phase II is related to a decrease in the growth rate of the sample. From the growth rates, the crystal surface free-energy product σσ_e was found equal to 17 × 10² erg²/cm⁴. The detailed analysis of the crystallization of the two phases reveals a complicated process which can be divided into four different steps: (a) growth of a disordered phase, Phase I; (b) nucleation of a higher birefringence structure; (c) propagation of a high birefringence phase; and (d) spherulitic growth, Phase II. The analysis of PDOL crystallization strongly suggests the presence of a hedrite → oval → spherulite transition: the hedrite formation corresponds to step (a), the oval formation to steps (b) and (c), and the spherulite formation to step (d).     

In-phantom dose verification of prostate IMRT and VMAT deliveries using plastic scintillation detectors

The goal of this work was to demonstrate the feasibility of using a plastic scintillation detector (PSD) incorporated into a prostate immobilization device to verify doses in vivo delivered during intensity-modulated radiation therapy (IMRT) and volumetric modulated-arc therapy (VMAT) for prostate cancer. The treatment plans for both modalities had been developed for a patient undergoing prostate radiation therapy. First, a study was performed to test the dependence, if any, of PSD accuracy on the number and type of calibration conditions. This study included PSD measurements of each treatment plan being delivered under quality assurance (QA) conditions using a rigid QA phantom. PSD results obtained under these conditions were compared to ionization chamber measurements. After an optimal set of calibration factors had been found, the PSD was combined with a commercial endorectal balloon used for rectal distension and prostate immobilization during external beam radiotherapy. This PSD-enhanced endorectal balloon was placed inside of a deformable anthropomorphic phantom designed to simulate male pelvic anatomy. PSD results obtained under these so-called “simulated treatment conditions” were compared to doses calculated by the treatment planning system (TPS). With the PSD still inserted in the pelvic phantom, each plan was delivered once again after applying a shift of 1 cm anterior to the original isocenter to simulate a treatment setup error.The mean total accumulated dose measured using the PSD differed the TPS-calculated doses by less than 1% for both treatment modalities simulated treatment conditions using the pelvic phantom. When the isocenter was shifted, the PSD results differed from the TPS calculations of mean dose by 1.2% (for IMRT) and 10.1% (for VMAT); in both cases, the doses were within the dose range calculated over the detector volume for these regions of steep dose gradient. Our results suggest that the system could benefit prostate cancer patient treatment by providing accurate in vivo dose reports during treatment and verify in real-time whether treatments are being delivered according to the prescribed plan.     

Radial oscillations of neutron stars in strong magnetic fields

The eigen frequencies of radial pulsations of neutron stars are calculated in a strong magnetic field. At low densities we use the magnetic BPS equation of state (EOS) similar to that obtained by Lai and Shapiro while at high densities the EOS obtained from the relativistic nuclear mean field theory is taken and extended to include strong magnetic field. It is found that magnetized neutron stars support higher maximum mass whereas the effect of magnetic field on radial stability for observed neutron star masses is minimal.