The benefit of plant growth-promoting microorganisms (PGPMs) as plant inoculants is influenced by a wide range of environmental factors. Therefore, microbial consortia products (MCPs) based on multiple PGPM strains with complementary functions, have been proposed as superior, particularly under challenging environmental conditions and for restoration of beneficial microbial communities in disturbed soil environments. To test this hypothesis, the performance of a commercial MCP inoculant based on 22 PGPM strains was investigated in greenhouse experiments with maize on three soils with contrasting pH, organic matter content and microbial activity, under different P and N fertilization regimes. Interestingly, the MCP inoculant stimulated root and shoot growth and improved the acquisition of macronutrients only on a freshly collected field soil with high organic matter content, exclusively in combination with stabilized ammonium fertilization. This was associated with transiently increased expression of AuxIAA5 in the root tissue, a gene responsive to exogenous auxin supply, suggesting root growth promotion by microbial auxin production as a major mode of action of the MCP inoculant. High microbial activity was indicated by intense expression of soil enzyme activities involved in C, N and P cycling in the rhizosphere (cellulase, leucine peptidase, alkaline and acid phosphatases) but without MCP effects. By contrast, the MCP inoculation did not affect maize biomass production or nutrient acquisition on soils with very little Corg and low microbial activity, although moderate stimulation of rhizosphere enzymes involved in N and P cycling was recorded. There was also no indication for MCP-induced solubilization of Ca-phosphates on a calcareous sub-soil fertilized with rock-phosphate. The results demonstrate that the combination of multiple PGPM strains with complementary properties as MCP inoculants does not necessarily translate into plant benefits in challenging environments. Thus, a better understanding of the conditions determining successful MCP application is mandatory.
The vagina is a promising site for both local and systemic drug delivery and represents an interesting administration route for compounds with poor oral bioavailability. Whereas most of the currently marketed dosage forms were designed as immediate release formulations, intravaginal rings (IVRs) offer the possibility of a controlled vaginal drug delivery over several weeks or months. For a long time, the development of IVRs was limited to steroid-releasing formulations. Recently, IVRs have witnessed a surge of new interest as promising delivery systems for microbicides. Therefore, various novel IVR designs have been introduced. To ensure that only safe and effective IVRs will be administered to patients, it is important to properly distinguish between IVRs with desired and undesired release performance. In vitro methods for evaluating drug release of IVRs that present with sufficient predictive capacity for in vivo drug release, and discriminatory power with regard to IVRs quality, are an essential tool for this purpose. The objective of the present review article is to present the current status of in vitro drug release testing of IVRs and to critically discuss current compendial and non-official in vitro drug release methods with regard to their discriminatory power and in vivo predictivity.
There has been a trend towards the development of novel vaginal dosage forms both for local therapy and systemic absorption. The growing number of vaginal dosage forms, however, presents with an increasing demand for appropriate in vitro test methods for ensuring a safe and reliable in vivo performance of each of the formulations. Application of biorelevant in vitro parameters, i.e., addressing in vivo parameters that significantly affect drug release from a vaginal dosage form in an in vitro test setup, could ensure that the results of the dissolution/drug release test are clinically meaningful and also predictive for detection of changes in the post-approval drug product. Thus, the development of predictive in vitro test methods for vaginal dosage forms is of great interest. A number of simulated vaginal fluids have been introduced in the recent past. In addition, several other genital fluids that could affect the intravaginal fluid composition, such as simulated cervical fluid/mucus, simulated intrauterine fluid, and simulated semen have been described in the literature. More frequent use of these media can be assumed, and future experiments will show if the current media will require more fine-tuning to even better reflect all physiological parameters that can affect drug release/dissolution in the vagina or if there is also a chance to simplify these media without losing their biorelevance.
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