Ultrasonic monitoring of drug loaded Pluronic F127 micellular hydrogel phase behaviour.

Pluronic hydrogels composed of PEO-PPO-PEO tri-block copolymers have received a lot of attention for their applicability to drug delivery. These systems can be injected into the body in a liquid form and then, in response to temperature changes, self-assemble into nano-sized micelles which ultimately aggregate to form a gel. The phase behaviour and effectiveness of Pluronic hydrogels as drug carriers is affected by the local thermal and ionic environment which is likely to be different from patient to patient. There is a current need for in vivo techniques to study the phase behaviour of Pluronic hydrogels and this work demonstrates an ultrasound approach for the study of drug loaded Pluronic F127 hydrogels. Ultrasound velocity and attenuation were both found to change with temperature and through validation with fluorescence spectroscopy it was determined that the temperature dependent micellation transition in the Pluronic solutions could be identified through relative changes in ultrasound velocity and attenuation as a function of temperature. This phase transition was more clearly detected through examination of the first and second derivatives of both ultrasound parameters with respect to temperature. Further this work demonstrates for the first time to our knowledge ultrasound characterisation studies on drug loaded Pluronics.

A review of cis-trans interplay between DNA sequences 5' to the (G)gamma- and beta-globin genes among Hb F-Malta-I heterozygotes/homozygotes and beta-thalassemia homozygotes/compound heterozygotes, and the effects of hydroxyurea on the Hb F/F-erythrocyte; the need for large multicenter trials.

The biosynthesis of Hb F in place of the deficient Hb A could be a suitable treatment for beta hemoglobinopathies. Among newborn Hb F-Malta-I heterozygotes, it could be shown that the XmnI sequence alone had little, if any effect on gamma-globin gene expression, but interplay with the (AT)(X)T(Y) sites in cis and in trans may occur. In contrast, while the XmnI sequence is clearly correlated with gamma-globin levels in anemic adult beta-thalassemia (thal) homozygotes, the effect on F-erythrocyte numbers and Hb F/F-erythrocyte appears independent of the (AT)(X)T(Y) sites. Even at levels of hydroxyurea (HU) as low as 1.65 mg/kg/day (vs. 10 mg/kg/day on the high dose regime) it can be shown that although even a small increase of Hb F could be obtained, the effect was rarely translated into an increase in circulating hemoglobin (Hb). In most cases, the elevated Hb F level was dependent on the XmnI sequence and was due to increased numbers of F-erythrocytes or Hb F/F-erythrocyte or both. It seems that the bone marrow of thalassemia homozygotes may be more sensitive to myelosuppression by HU possibly due to medullary inflammation. While the data are consistent with loop models of globin switching mechanisms, there is urgent need for large, hypothesis driven, multicenter trials of molecules that could maintain or re-induce high Hb F levels in beta-thal and subject to genetic and epigenetic constraints including inflammation.