Expandable drug delivery systems are one of many gastroretentive delivery systems which have emerged during the last few years. Expandable systems are usually folded in a capsule and expand to dimensions greater than the pyloric sphincter upon contact with gastric fluid. This prevents them from being evacuated by gastric emptying. The main objective of developing such systems is to increase the residence time of a specific drug in stomach; controlling its release, increasing its bioavailability and decreasing its side effects and dosing frequency. An expandable gastroretentive drug delivery system containing Gabapentin was developed using experimental design (D-optimal reduced quadratic design). This system was able to unfold at stomach pH in less than 15 minutes and obtain a controlled release of 78.1 ± 4.7% in 6 hours following zero-order release kinetic model. It is rigid in stomach and its rigidity decreases at intestinal pH. FTIR analysis indicated the occurrence of hydrogen bonding in Gabapentin when present in the developed system, which might be responsible for the drug’s controlled release. XRD analysis indicated that Gabapentin physical properties changed from crystalline in the typical state to amorphous in the developed system.
Parental exposure to insults was initially considered safe if stopped before conception. In the present investigation, paternal or maternal preconception exposure to the neuroteratogen chlorpyrifos was investigated in a well-controlled avian model (Fayoumi) and compared to pre-hatch exposure focusing on molecular alterations. The investigation included the analysis of several neurogenesis, neurotransmission, epigenetic and microRNA genes. A significant decrease in the vesicular acetylcholine transporter (SLC18A3) expression was detected in the female offspring in the three investigated models: paternal (57.7%, p < 0.05), maternal (36%, p < 0.05) and pre-hatch (35.6%, p < 0.05). Paternal exposure to chlorpyrifos also led to a significant increase in brain-derived neurotrophic factor (BDNF) gene expression mainly in the female offspring (27.6%, p < 0.005), while its targeting microRNA, miR-10a, was similarly decreased in both female (50.5%, p < 0.05) and male (56%, p < 0.05) offspring. Doublecortin’s (DCX) targeting microRNA, miR-29a, was decreased in the offspring after maternal preconception exposure to chlorpyrifos (39.8%, p < 0.05). Finally, pre-hatch exposure to chlorpyrifos led to a significant increase in protein kinase C beta (PKCß; 44.1%, p < 0.05), methyl-CpG-binding domain protein 2 (MBD2; 44%, p < 0.01) and 3 (MBD3; 33%, p < 0.05) genes expression in the offspring. Although extensive studies are required to establish a mechanism–phenotype relationship, it should be noted that the current investigation does not include phenotype assessment in the offspring.
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