Two-phase matrices for the controlled release of therapeutic proteins.

Controlled and sustained delivery of therapeutic proteins is crucial for achieving desired effects in wound healing applications. Yet, this remains a challenge in growth factor delivery for bone tissue engineering. Current delivery systems can lead to negative side effects, such as ectopic bone growth and cancer, due to the over administration of growth inducing proteins. Here, we have developed a two-phase system for the controlled release of therapeutic proteins. The system consists of protein-loaded poly(methacrylic acid)-based nanoparticles conjugated to chitosan scaffolds. The effect of co-monomer hydrophilicity and crosslinking density on nanoparticle properties was evaluated. It was found that the release kinetics of model therapeutic proteins were dependent on nanoparticle hydrophilicity. The chitosan scaffold, chosen for its biocompatibility and osteogenic properties, provided additional barriers to diffusion and promoted nanoparticle retention, leading to more sustained protein delivery. Additionally, the ability of MC3T3-E1 pre-osteoblast cells to proliferate on scaffolds with and without conjugated nanoparticles was evaluated and all scaffolds were shown to promote cell growth. The results demonstrate that the two-phase scaffold system presents a superior strategy for the sustained and controlled release of therapeutic proteins for bone tissue engineering applications.

RNA Taste Is Conserved in Dipteran Insects.

BACKGROUND: Ribonucleosides and RNA are an underappreciated nutrient group essential during Drosophila larval development and growth. Detection of these nutrients requires at least one of the 6 closely related taste receptors encoded by the Gr28 genes, one of the most conserved insect taste receptor subfamilies. OBJECTIVES: We investigated whether blow fly larvae and mosquito larvae, which shared the last ancestor with Drosophila about 65 and 260 million years ago, respectively, can taste RNA and ribose. We also tested whether the Gr28 homologous genes of the mosquitoes Aedes aegypti and Anopheles gambiae can sense these nutrients when expressed in transgenic Drosophila larvae. METHODS: Taste preference in blow flies was examined by adapting a 2-choice preference assay that has been well-established for Drosophila larvae. For the mosquito Aedes aegypti, we developed a new 2-choice preference assay that accommodates the aquatic environment of these insect larvae. Finally, we identified Gr28 homologs in these species and expressed them in Drosophila melanogaster to determine their potential function as RNA receptors. RESULTS: Larvae of the blow fly Cochliomyia macellaria and Lucilia cuprina are strongly attracted to RNA (0.5 mg/mL) in the 2-choice feeding assays (P < 0.05). Similarly, the mosquito Aedes aegypti larvae showed a strong preference for RNA (2.5 mg/mL) in an aquatic 2-choice feeding assay. Moreover, when Gr28 homologs of Aedes or Anopheles mosquitoes are expressed in appetitive taste neurons of Drosophila melanogaster larvae lacking their Gr28 genes, preference for RNA (0.5 mg/mL) and ribose (0.1 M) is rescued (P < 0.05). CONCLUSIONS: The appetitive taste for RNA and ribonucleosides in insects emerged about 260 million years ago, the time mosquitoes and fruit flies diverged from their last common ancestor. Like sugar receptors, receptors for RNA have been highly conserved during insect evolution, suggesting that RNA is a critical nutrient for fast-growing insect larvae.

Recent advances in glucose-responsive insulin delivery systems: novel hydrogels and future applications.

Over the past several decades, there have been major advancements in the field of glucose sensing and insulin delivery for the treatment of type I diabetes mellitus. The introduction of closed-loop insulin delivery systems that deliver insulin in response to specific levels of glucose in the blood has shifted significantly the research in this field. These systems consist of encapsulated glucose-sensitive components such as glucose oxidase or phenylboronic acid in hydrogels, microgels or nanoparticles. Since our previous evaluation of these systems in a contribution in 2004, new systems have been developed. Important improvements in key issues, such as consistent insulin delivery over an extended period of time have been addressed. In this contribution, we discuss recent advancements over the last 5 years and present persisting issues in these technologies that must be overcome in order for these systems to be applicable in patients.