Surface tension at the surface-to-air interface is a physico-chemical property of liquid pharmaceutical formulations that are often overlooked. To determine if a trend between surface tension and route of administration exists, a suite of oral, nasal, and ophthalmic drug formulations were analyzed. The surface tension at the surface-to-air interface of the oral formulations studied were in or above the range of the surface tension of gastric, duodenum, and jejunum fluids. The range of surface tensions for oral formulations were 36.6–64.7 dynes/cm. Nasal formulations had surface tensions below that of the normal mucosal lining fluid with a range of 30.3–44.9 dynes/cm. Ophthalmic OTC formulations had the largest range of surface tensions at the surface-to-air interface of 34.3–70.9 dynes/cm; however, all formulations indicated for treatment of dry eye had surface tensions higher than that of normal tears, while those for treatment of red eye had surface tensions below. Therefore, surface tension at the surface-to-air interface of liquid formulations is dependent on the route of administration, environment at site of introduction, and for ophthalmics, what the formulation is indicated for.

Parkinson’s disease (PD) is characterized by multiple symptoms including olfactory dysfunction, whose underlying mechanisms remain unclear. Here, we explored pathologic changes in the olfactory pathway of transgenic (Tg) mice of both sexes expressing the human A30P mutant α-synuclein (α-syn; α-syn-Tg mice) at 6–7 and 12–14 months of age, representing early and late-stages of motor progression, respectively. α-Syn-Tg mice at late stages exhibited olfactory behavioral deficits, which correlated with severe α-syn pathology in projection neurons (PNs) of the olfactory pathway. In parallel, olfactory bulb (OB) neurogenesis in α-syn-Tg mice was reduced in the OB granule cells at six to seven months and OB periglomerular cells at 12–14 months, respectively, both of which could contribute to olfactory dysfunction. Proteomic analyses showed a disruption in endocytic and exocytic pathways in the OB during the early stages which appeared exacerbated at the synaptic terminals when the mice developed olfactory deficits at 12–14 months. Our data suggest that (1) the α-syn-Tg mice recapitulate the olfactory functional deficits seen in PD; (2) olfactory structures exhibit spatiotemporal disparities for vulnerability to α-syn pathology; (3) α-syn pathology is restricted to projection neurons in the olfactory pathway; (4) neurogenesis in adult α-syn-Tg mice is reduced in the OB; and (5) synaptic endocytosis and exocytosis defects in the OB may further explain olfactory deficits.SIGNIFICANCE STATEMENTOlfactory dysfunction is a characteristic symptom of Parkinson’s disease (PD). Using the human A30P mutant α-synuclein (α-syn)-expressing mouse model, we demonstrated the appearance of olfactory deficits at late stages of the disease, which was accompanied by the accumulation of α-syn pathology in projection neurons (PNs) of the olfactory system. This dysfunction included a reduction in olfactory bulb (OB) neurogenesis as well as changes in synaptic vesicular transport affecting synaptic function, both of which are likely contributing to olfactory behavioral deficits.

Parkinson Disease (PD) is characterized by multiple symptoms including olfactory dysfunction, whose underlying mechanisms remain unclear. Here, we explored pathological changes in the olfactory pathway of transgenic (Tg) mice expressing the human A30P mutant alpha-synuclein (alpha-syn) (alpha-syn-Tg mice) at 6-7 and 12-14 months of age, representing early and late-stages of motor progression, respectively. alpha-Syn-Tg mice at late stages exhibited olfactory behavioral deficits, which correlated with severe alpha-syn pathology in projection neurons of the olfactory pathway. In parallel, olfactory bulb (OB) neurogenesis in alpha-syn-Tg mice was reduced in the OB granule cells at 6-7 months, and OB periglomerular cells at 12-14 months, respectively, both of which could contribute to olfactory dysfunction. Proteomic analyses showed a disruption in endo- and exocytic pathways in the OB during the early stages which appeared exacerbated at the synaptic terminals when the mice developed olfactory deficits at 12-14 months. Our data suggest that, 1) the alpha-syn-Tg mice recapitulate the olfactory functional deficits seen in PD; 2) olfactory structures exhibit spatiotemporal disparities for vulnerability to alpha-syn pathology; 3) alpha-syn pathology is restricted to projection neurons in the olfactory pathway; 4) neurogenesis in adult alpha-syn-Tg mice is reduced in the OB; and 5) synaptic endo- and exocytosis defects in the OB may further explain olfactory deficits.