Microbicide delivery: formulation technologies and strategies

Purpose of review: The aim of this article is to summarize the latest information on microbicide formulations for prevention of sexual transmission of HIV infection in women. Recent findings: Although early microbicide formulations were conventionally coitally dependent gel products, new technologies are being developed for vaginal delivery of anti-HIV agents. Intravaginal rings for delivery of microbicides, for example, are being developed and evaluated clinically. Safety and acceptability data are available for many microbicide gels and for one microbicide intravaginal ring. Other microbicide formulations in development for once daily or other vaginal administration strategies include films, tablets, and ovules. Various microbicide formulations for rectal administration are also in development. Summary: New microbicide formulations in development are addressing many of the issues with the original gels such as coital dependency, frequency of use, acceptability, compliance, cost, and adaptability to large-scale production. All of these dosage forms are promising options for safe, effective, and acceptable microbicide products.

System oriented neural networks - Problem formulation, methodology and application

A novel methodology is proposed for the development of neural network models for complex engineering systems exhibiting nonlinearity. This method performs neural network modeling by first establishing some fundamental nonlinear functions from a priori engineering knowledge, which are then constructed and coded into appropriate chromosome representations. Given a suitable fitness function, using evolutionary approaches such as genetic algorithms, a population of chromosomes evolves for a certain number of generations to finally produce a neural network model best fitting the system data. The objective is to improve the transparency of the neural networks, i.e. to produce physically meaningful

Comparisons of plankton at 59 degrees N and 37 degrees N during two Lagrangian drift experiments in the North Atlantic in June and July 1996

Data are summarised for two Lagrangian experiments in the North Atlantic in early summer 1996. At 59 degreesN 20 degreesW, plankton dynamics was studied in an SF, tracer release experiment within a mesoscale eddy over a 9-day period. At 37 degreesN 20 degreesW, a second experiment followed a drifting buoy for 7 days. The data obtained in these two experiments have been averaged for 3 depth strata; the euphotic zone, the surface mixed layer (SML), and the seasonal thermocline immediately beneath the surface mixed layer. At 59 degreesN, the euphotic zone was only marginally deeper than the SML, but at 37 degreesN the SML was ca 30 m and the euphotic depth was ca 110 m. At 37 degreesN, nutrient concentrations in the SML were low but significant new production occurred in the thermocline because of light penetration into the nutricline. The particulate organic carbon (POC) concentration of the SML at 59 degreesN was 13-15 mu mol C kg(-1), but at 37 degreesN POC concentrations were 4 mu mol C kg(-1). These POC measurements include biota and detritus. As a way of investigating latitudinal differences in the plankton communities, estimates have been made of the carbon and nitrogen content of phytoplankton, bacterioplankton, microzooplankton and mesozooplankton. At both 59 degreesN and 37 degreesN, phytoplankton was the largest component, accounting for ca 50% of the planktonic biomass in the SML. At 59 degreesN, microzooplankton was 16% of the planktonic carbon, but at 37 degreesN this reduced to 8% of the total. Mesozooplankton was a relatively constant proportion (ca 20%) of the planktonic carbon in the SML at both 59 degreesN and 37 degreesN. Bacterioplankton was 14% of the biomass at 59 degreesN, increasing to 24% in the microbial loop-dominated system at 37 degreesN. Mean carbon fixation rate in the oligotrophic southern station was 24% of that at the north, with more carbon fixation below the SML at 37 degreesN than at 59 degreesN. Respiration rates showed little variation with latitude, and the rates at 37 degreesN were 80% of those at 59 degreesN. Nitrate and ammonium uptake rates were very low in the oligotrophic conditions in the SML at 37 degreesN, but nitrate uptake in the euphotic zone was comparable to that at 59 degreesN. Ammonium uptake by phytoplankton was also significantly greater at 37 degreesN, in both the euphotic zone and thermocline, but uptake in the SML was only 20% of that in the SML at 59 degreesN. (C) 2001 Elsevier Science Ltd. All rights reserved.

Influence of Formulation Factors on PpIX Production and Photodynamic Action of Novel ALA-loaded Microparticles

A novel 5-aminolevulinic acid (ALA)-containing microparticulate system was produced recently, based on incorporation of ALA into particles prepared from a suppository base that maintains drug stability during storage and melts at skin temperature to release its drug payload. The novel particulate system was applied to the skin of living animals, followed by study of protoporphyrin IX (PpIX) production. The effect of formulating the microparticles in different vehicles was investigated and also the phototoxicity of the PpIX produced using a model tumour. Particles formulated in propylene glycol gels (10% w/w ALA loading) generated the highest peak PpIX fluorescence levels in normal mouse skin. Peak PpIX levels induced in skin overlying subcutaneously implanted WiDr tumours were significantly lower than in normal skin for both the 10% w/w ALA microparticles alone and the 10% w/w ALA microparticles in propylene glycol gels during continuous 12 h applications. Tumours not treated with photodynamic therapy continued to grow over the 17 days of the anti-tumour study. However, those treated with 12 h applications of either the 10% w/w ALA microparticles alone or the 10% w/w ALA microparticles in propylene glycol gel followed by a single laser irradiation showed no growth. The gel formulation performed slightly better once again, reducing the tumour growth rate by approximately 105%, compared with the 89% reduction achieved using particles alone. Following the promising results obtained in this study, work is now going on to prepare particle-loaded gels under GMP conditions with the aim of initiating an exploratory clinical trial.

Genetic programming based formulation for fresh and hardened properties of self-compacting concrete containing pulverised fuel ash

Self-compacting concrete (SCC) flows into place and around obstructions under its own weight to fill the formwork completely and self-compact without any segregation and blocking. Elimination of the need for compaction leads to better quality concrete and substantial improvement of working conditions. This investigation aimed to show possible applicability of genetic programming (GP) to model and formulate the fresh and hardened properties of self-compacting concrete (SCC) containing pulverised fuel ash (PFA) based on experimental data. Twenty-six mixes were made with 0.38 to 0.72 water-to-binder ratio (W/B), 183–317 kg/m³ of cement content, 29–261 kg/m³ of PFA, and 0 to 1% of superplasticizer, by mass of powder. Parameters of SCC mixes modelled by genetic programming were the slump flow, JRing combined to the Orimet, JRing combined to cone, and the compressive strength at 7, 28 and 90 days. GP is constructed of training and testing data using the experimental results obtained in this study. The results of genetic programming models are compared with experimental results and are found to be quite accurate. GP has showed a strong potential as a feasible tool for modelling the fresh properties and the compressive strength of SCC containing PFA and produced analytical prediction of these properties as a function as the mix ingredients. Results showed that the GP model thus developed is not only capable of accurately predicting the slump flow, JRing combined to the Orimet, JRing combined to cone, and the compressive strength used in the training process, but it can also effectively predict the above properties for new mixes designed within the practical range with the variation of mix ingredients.