Capability verification of the beam delivery system in the superficially-placed tumor therapy terminal at HIRFL

The passive beam delivery system in the superficially-placed tumor therapy terminal at Heavy Ion Researc h Facility in Lanzhou (HIRFL), which includes two orthogonal dipole magnets as scanning system, a motor-driven energy degrader as range-shifter, series of ridge filters as range modulator and a multileaf collimator, is introduced in detail. The capacities of its important components and the whole system have been verified experimentally. The tests of the ridge filter for extending Bragg peak and the range shifter for energy adjustment show both work well. To examine the passive beam delivery system, a beam shaping experiment were carried out, simulating a three-dimensional (3D) conformal irradiation to a tumor. The encouraging experimental result confirms that 3D layer-stacking conformal irradiation can be performed by means of the passive system. The validation of the beam delivery system establishes a substantial basis for upcoming clinical trial for superficially-placed tumors with heavy ions in the therapy terminal at HIRFL.

Conformal irradiation to moving targets in heavy ion radiotherapy with raster-scanning beam delivery system: (II) feasibility experiments

Within the framework of the pilot heavy-ion therapy facility at GSI equipped with an active beam delivery system of advanced raster scanning technique, a feasibility study on actively conformal heavy-ion irradiation to moving tumors has been experimentally conducted. Laterally, real-time corrections to the beam scanning parameters by the raster scanner, leading to an active beam tracing, compensate for the lateral motion of a target volume. Longitudinally, a mechanically driven wedge energy degrader (called depth scanner) is applied to adjust the beam energy so as to locate the high-dose Bragg peak of heavy ion beam to the slice under treatment for the moving target volume. It has been experimentally shown that compensations for lateral target motion by the raster scanner and longitudinal target shift by the depth scanner are feasible.

Prostate cancer cell-specific VEGF siRNA delivery system using cell targeting peptide conjugated polyplexes

A polymeric gene carrier was developed to deliver vascular endothelial growth factor (VEGF) small interfering RNA (siRNA) for prostate cancer cells in a target-specific manner. Prostate cancer-binding peptide (PCP) was conjugated with polyethylenimine (PEI) via a poly(ethylene glycol) (PEG) linker (PEI-PEG-PCP). The PEI-PEG-PCP conjugate could effectively condense siRNA to form stable polyelectrolyte complexes (polyplexes) with an average diameter of approximately 150 nm in an aqueous solution. VEGF siRNA/PEI-PEG-PCP polyplexes exhibited significantly higher VEGF inhibition efficiency than PCP-unmodified polycationic carriers (PEI-PEG or PEI) in human prostate carcinoma cells (PC-3 cells). The enhanced gene silencing activity of VEGF siRNA/PEI-PEG-PCP was maintained even under serum conditions, owing to the steric stabilization of the polyplexes with hydrophilic PEG grafts. Confocal microscopic studies revealed that the siRNA/PEI-PEG-PCP polyplexes were delivered into PC-3 cells in a PCP ligand-specific manner.

Luminescence functionalization of SBA-15 by YVO4 : Eu3+ as a novel drug delivery system

Luminescence functionalization of the ordered mesoporous SBA-15 silica was realized by depositing a YVO4:Eu3+ phosphor layer on its surface via the Pechini sol-gel process, resulting in the formation of the YVO4:Eu3+@SBA-15 composite material. This material, which combines the mesoporous structure of SBA-15 and the strong red luminescence property of YVO4:Eu3+, can be used as a novel functional drug delivery system. The structure, morphology, porosity, and optical properties of the materials were well characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, N-2 adsorption, and photoluminescence spectra. As expected, the pore volume, surface area, and pore size of SBA-15 decrease in sequence after deposition of the YVO4:Eu3+ layer and the adsorption of ibuprofen (IBU, drug). The IBU-loaded YVO4:Eu3+@SBA-15 system still shows the red emission of Eu3+ (617 nm, D-5(0)-F-7(2)) under UV irradiation and the controlled drug release property. Additionally, the emission intensity of Eu3+ increases with an increase in the cumulative released amount of IBU in the system, making the extent of drug release easily identifiable, trackable, and monitorable by the change of luminescence. The system has great potential in the drug delivery and disease therapy fields.

MCM-41 functionalized with YVO4 : Eu3+: a novel drug delivery system

Luminescence functionalization of ordered mesoporous MCM-41 silica was realized by depositing a YVO4:Eu3+ phosphor layer on its surface via the Pechini sol-gel process. This material, which combines the mesoporous structure of MCM-41 and the strong red luminescence property of YVO4: Eu3+, has been studied as a host carrier for drug delivery/release systems. The structure, morphology, texture and optical properties of the materials were well characterized by x-ray diffraction ( XRD), Fourier infrared spectroscopy ( FT-IR), transmission electron microscopy ( TEM), N-2 adsorption and photoluminescence ( PL) spectra. The results indicated that the specific surface area and pore volume of MCM-41, which were directly correlated to the drug-loading amount and ibuprofen ( IBU) release rate, decreased in sequence after deposition of YVO4:Eu3+ and loading of IBU as expected. The IBU-loaded YVO4:Eu3+@ MCM-41 system still showed red luminescence under UV irradiation ( 365 nm) and a controlled release property for IBU. In addition, the emission intensity of Eu3+ increases with an increase in the cumulative released amount of IBU, making the extent of drug release easily identified, tracked and monitored by the change of luminescence, which demonstrates its potential application in drug delivery/release systems.

Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

Local delivery of chlorhexidine using a tooth-bonded delivery system

Films containing 20% w/w chlorhexidine base (particle size 63-125 mu m) in poly(epsilon-caprolactone), MW 35 000-45 000, were prepared by solvent evaporation and sections attached to the mesio-lingual and mesio-buccal surfaces of the lower first molar in healthy volunteers. Saliva (