Population Effects of Calcium Phosphate Nanoparticles in Drosophila melanogaster: The Effects of Phase Composition Crystallinity and the Pathway of Formation

摘要

Unpredictable biological response due to the finest nanostructural variations is one of the hallmarks of nanoparticles. Because of this erratic behavior of nanoparticles in living systems, thorough analyses of biosafety must precede the analyses of the pharmacotherapeutic efficacy and simple animal models are ideal for such purposes. Drosophila melanogaster, the common fruit fly, is an animal model capable of giving a fast, high-throughput response as to the safety and efficacy of drug delivery carriers and other pharmacological agents, while minimizing the suffering imposed onto animals in more complex in vivo models. Here we studied the effects on the viability and fertility of D. melanogaster due to variations in phase composition, crystallinity, and the pathway of formation of four different calcium phosphate (CP) nanopowders consumed orally. To minimize the effect of other nanostructural variables, CP nanopowders were made to possess highly similar particle sizes and morphologies. The composition of CP affected the fecundity of flies, but so did crystallinity and the pathway of formation. Both the total number of eclosed viable flies and pupae in populations challenged with hydroxyapatite (HAP) greatly exceeded those in control populations. Viability was adversely affected by the only pyrophosphate tested (CPP) and by the metastable and the most active of all CP nanopowders analyzed: the amorphous CP (ACP). The pupation peak was delayed and the viable fly to-pupa ratio increased in all the CP-challenged populations. F1 CPP population, whose viability was most adversely affected by the CP consumption, when crossed, produced the largest number of F2 progeny under regular conditions, possibly pointing to stress as a positive evolutionary drive. The positive effect of HAP on fertility of fruit flies may be due to its slow absorption and the activation of calmodulin during the transit of oocytes through the reproductive tract of fertilized females. Exerted in the prepupation stage, the effect of CP is thus traceable beyond the instar larval stage and to the oogenesis stage of the Drosophila lifecycle.