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Despite research efforts full potential of siRNA-based therapeutics has not yet been fully realized due to a need for suitable, effective delivery formulations. Here, we examine a potential of a new class of water-soluble chitosans as siRNA platform for pulmonary delivery. The system is based on piperazine-substituted chitosans, a material designed to integrate established, safe application of chitosan for mucosal administration with novel properties: the piperazine-substituted chitosans are freely water-soluble at physiological pH, possess low cytotoxicity (no significant reduction in cell viability up to 0.1 mg/ml), and provide efficient incorporation of siRNA into sub-300 nm colloidal complexes (at relatively low polymer/siRNA ratio of 5:1). In vitro, the complexes achieved silencing of a model gene at a level of 40–80%, when tested in a panel of lung epithelial cells. Considering the formulation ‘developability’, there were no significant changes in the complexes’ size and integrity on aerosolisation by microsprayer (PenCentury™) device. Following intratracheal aerolisation, the complexes deposited throughout the lung, although relatively inhomogeneously, as judged from IVIS imaging of the isolated mouse lung (visualizing DY647-siRNA). In vivo data illustrate absence of adverse effects on repeated administration of complexes and significant tumor reduction in atopical lung cancer model in mice. Altogether, the data illustrates potential of substituted chitosan derivatives to be utilized as a safe system for inhalation delivery of siRNA.

Objective. To investigate the association between faltering growth in children and maternal postnatal depression. Methods. Children aged [less than or equal to] 2 years were identified from community child health surveillance records if their weights fell across 2 centile channels on standardized growth charts or fell below the second centile. Mothers of these index children were invited to complete the Edinburgh Postnatal Depression Scale and the anxiety subscale of the Hospital Anxiety and Depression Scale. Those who scored above threshold values on either scale were interviewed with the revised Clinical Interview Schedule. Matched control children were obtained from health visitor records, and records of their weights were obtained. Mothers of control children completed the same questionnaires. Results. A total of 196 index children and 567 control children were studied. Significantly more mothers in the index group scored above the threshold for both the Edinburgh Postnatal Depression Scale (33% vs 22%; odds ratio [OR]: 1.71; 95% confidence interval [CI]: 1.16-2.53) and the Hospital Anxiety and Depression Scale (24% vs 13%; OR: 2.08; 95% CI: 1.33-3.25) questionnaires. Furthermore, clinical interviews with these mothers demonstrated that 21% of the index group and 11% of the control group fulfilled criteria for depressive episode (OR: 1.88; 95% CI: 1.21-2.94). Conclusions. Depression in mothers of children with faltering growth during the first 2 years of life is significantly greater than in mothers of children who are gaining weight appropriately. In view of the high rates of maternal depression in children with poor weight gain, clinical management at presentation of either problem should focus on both members of the mother-child dyad and on the interaction between mother and child. These findings have implications for all professionals who work in primary and secondary health care. ABBREVIATIONS. FTT, failure to thrive; PND, postnatal depression; EPDS, Edinburgh Postnatal Depression Scale; HADS, Hospital Anxiety and Depression Scale; CIS-R, Revised Clinical Interview Schedule; OR, odds ratios; CI, confidence interval., Faltering growth and failure to thrive are overlapping descriptive terms applied to children who have poor weight gain compared with standard growth rates. Despite there being no consistent definition for [...]