Neighboring Group-Controlled Hydrolysis: Towards “Designer” Drug Release Biomaterials

To give the first demonstration of neighboring group-controlled drug delivery rates, a series of novel, polymerizable ester drug conjugates was synthesized and fully characterized. The monomers are suitable for copolymerization in biomaterials where control of drug release rate is critical to prophylaxis or obviation of infection. The incorporation of neighboring group moieties differing in nucleophilicity, geometry, and steric bulk in the conjugates allowed the rate of ester hydrolysis, and hence drug liberation, to be rationally and widely controlled. Solutions (2.5 x 10-5 mol dm-3) of ester conjugates of nalidixic acid incorporating pyridyl, amino, and phenyl neighboring groups hydrolyzed according to first-order kinetics, with rate constants between 3.00 ( 0.12 10-5 s -1 (fastest) and 4.50 ( 0.31 10- 6 s-1 (slowest). The hydrolysis was characterized using UV-visible spectroscopy. When copolymerized with poly(methyl methacrylate), free drug was shown to elute from the resulting materials, with the rate of release being controlled by the nature of the conjugate, as in solution. The controlled molecular architecture demonstrated by this system offers an attractive class of drug conjugate for the delivery of drugs from polymeric biomaterials such as bone cements in terms of both sustained, prolonged drug release and minimization of mechanical compromise as a result of release. We consider these results to be the rationale for the development of 'designer' drug release biomaterials, where the rate of required release can be controlled by predetermined molecular architecture.

Rural Development Group Politics. A hidden cost?

I challenge the popular notion of European rural development group dynamics and argue for a better understanding of the role of micro-politics as a means of enhancing the performance of these groups. The views are research based and have relevance to the broader rural development and regeneration sector. Micro-politics involves knowledge, power, trust, perceptions, understanding, social networks, values and traits that arise as a result of individuals interacting within a group whilst working on a shared goal, such as rural development. The monetary and time costs to a community of failing to address micro-politics and nurture positive group relations are considerable. These include time spent in unproductive meetings and poorly prioritized—and ultimately unsuccessful—funding applications as a result of failure to agree priorities. Successful groups rely on individuals interacting in a way that achieves a greater social good. Mutual trust amongst the actors lies at the heart of effective group activity. Effective management of micro-politics requires steps to nurture a culture of mutual trust to ensure that rural development actors co-operate rather than play destructive games with one another. A case study example of a relatively straightforward approach illustrates how this might be done in practice.