In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis

Abstract Background Sustained drug delivery is a large unmet clinical need in glaucoma. Here, we incorporated a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor, CCG-222740, into slow release large unilamellar vesicles derived from the liposomes DOTMA (1,2-di-O-octadecenyl-3-trimethylammonium propane) and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), and tested their effects in vitro and in vivo. Results The vesicles were spherical particles of around 130 nm and were strongly cationic. A large amount of inhibitor could be incorporated into the vesicles. We showed that the nanocarrier CCG-222740 formulation gradually released the inhibitor over 14 days using high performance liquid chromatography. Nanocarrier CCG-222740 significantly decreased ACTA2 gene expression and was not cytotoxic in human conjunctival fibroblasts. In vivo, nanocarrier CCG-222740 doubled the bleb survival from 11.0 ± 0.6 days to 22.0 ± 1.3 days (p = 0.001), decreased conjunctival scarring and did not have any local or systemic adverse effects in a rabbit model of glaucoma filtration surgery. Conclusions Our study demonstrates proof-of-concept that a nanocarrier-based formulation efficiently achieves a sustained release of a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor and prevents conjunctival fibrosis in an established rabbit model of glaucoma filtration surgery.https://deepblue.lib.umich.edu/bitstream/2027.42/146540/1/12951_2018_Article_425.pd

Thyroid homeostasis in mother–child pairs in relation to maternal iodine status: the MISA study

BACKGROUND/OBJECTIVES: Iodine deficiency during pregnancy may influence maternal and foetal thyroid function with the risk of causing neurocognitive and psychomotor deficits in the offspring. The objective of this study was to assess iodine status in pregnant women from Northern Norway and to investigate the influence of iodine status on maternal and infant thyroid function. SUBJECTS/METHODS: Women from the Northern Norway Mother-and-Child contaminant Cohort Study (MISA) donated a blood and urine sample at three visits during their pregnancy and postpartum period (in second trimester, 3 days and 6 weeks after delivery. N = 197). Women were assigned to iodine status groups according to urine iodine concentrations (UICs) in second trimester and mixed effects linear models were used to investigate potential associations between iodine status and repeated measurements of thyroid-stimulating hormone (TSH), thyroid hormones (THs), TH-binding proteins and thyroid peroxidase antibodies. Associations between maternal iodine status and TSH in heel prick samples from the infants were investigated with linear regression. RESULTS: Median UIC in second trimester was 84 μg/l (range 18–522) and 80% had UIC below recommended level (o150 μg/l). Iodine-deficient women had higher concentrations of T3, FT3 and FT4 (estimated differences (confidence intervals) of 0.10 nmol/l (0.01, 0.17), 0.16 pmol/l (0.05, 0.26) and 0.45 pmol/l (0.10, 0.78), respectively) compared with iodine-sufficient women. The concentrations varied within normal reference ranges, but the majority of women with subclinical hypothyroidism were iodine deficient. Maternal iodine status did not influence infant TSH concentrations. CONCLUSIONS: This study indicate iodine deficiency among pregnant women in Norway. Iodine status during pregnancy influences maternal thyroid homeostasis and is therefore a risk factor for foetal and infant development

Injectable Gels for Dental and Craniofacial Applications

The use of injectable scaffolds is considered a promising approach in craniofacial tissue regeneration, as they can be introduced with minimally invasive surgery, thus reducing the risk of surgery complications and improving postoperative recovery. In this chapter, comprehensive descriptions of chemically and physically cross-linked hydrogels that can be used as injectable scaffolds for dental and craniofacial application are presented. Nanocomposite hydrogels, in which nano-sized particles may serve as reinforcing agents and impart functionality to the hydrogels, are also discussed. Special attention is given to peptide amphiphiles which can self-assemble into supramolecular configuration mimicking the extracellular matrix (ECM) structure. Finally, injectable microspheres and different techniques of fabrication are discussed in this chapter