Celecoxib (CLX), a selective COX-2 inhibitor, is a biopharmaceutics classification system (BCS) class II drug with its bioavailability being limited by thepoor aqueoussolubility. The purpose of this study was to develop and optimize CLX nanocrystalline(CLX-NC) solid dispersion prepared by the wet medium millingtechnique combined with lyophilizationto enhance oral bioavailability. In formulation screening, the resulting CLX-NC usingpolyvinylpyrrolidone (PVP) VA64 and sodiumdodecyl sulfate (SDS) as combined stabilizers showed the minimum particle size and a satisfactory stability. The formulation and preparation processwere further optimized by central composite experimentaldesign with PVP VA64 concentration (X₁), SDS concentration (X₂) and milling times (X₃) as independent factors and particle size (Y₁), polydispersity index (PDI, Y₂) and zeta potential (Y₃) as response variables. The optimal condition was determined as a combination of 0.75% PVP VA64, 0.11% SDS with milling for 90 min.The particle size, PDI and zeta potential of optimized CLX-NC were found to be 152.4 ± 1.4 nm, 0.191 ± 0.012 and −34.4 ± 0.6 mV, respectively. The optimized formulation showed homogeneous rod-like morphology as observed by scanning electron microscopy and was in a crystalline state as determined by differential scanning calorimetry and powder X-ray diffraction. In a storage stability study, optimized CLX-NC exhibited an excellent physical stability during six months’ storage at both the refrigeration and room conditions. In vivo pharmacokinetic research in Sprague-Dawley ratsdisplayed that C_max and AUC_0–∞ of CLX-NC were increased by 2.9 and 3.1 fold, compared with physical mixture. In this study, the screening and optimizing strategy of CLX-NC formulation represents a commercially viable approach forenhancing the oral bioavailability of CLX.

Phosphatidylserine (PS) is a major anionic phospholipid constituent of membrane bilayers, which is specifically enriched in the cytoplasmic leaflet, has functions of regulating the intracellular signaling pathways of neuronal survival and differentiation, and acts as a neurotransmitter to control the activity of neurons. Oil-in-water (O/W) emulsions could improve the bio-availability of PS. Thus, there is a high level of interest in PS emulsion because of its purported health benefits. However, because of high viscosity and poor fluidity, it remains difficult to make the emulsion. A detailed analysis with suited biophysical methods would help to better understand the processes on a molecular level. Therefore, the main aim of the present study was to engineer and characterize a stable O/W phosphatidylserine emulsion. Furthermore, the effect of emulsifiers mixture, whey protein isolate (WPI), and Tween 80 (T80), as well as the oil phase was systematically evaluated. The key parameters were the chain length and the degree of nonsaturation (sunflower oil, a long-chain triglycerides [LCTs] or a medium-chain triglycerides [MCTs]). Small droplets of emulsions could be obtained by adjusting the type of emulsifier and the LCT/MCT ratio. A stable PS emulsion characterized by a smaller droplet size, higher negative zeta-potential, lower centrifugal stability constant, and longer storage time was produced by MCTs T80 (2.0%, w/w) with T80 (2.0%, w/w) as the emulsifier, and by LCTs with the WPI (0.5%, w/w)—T80 (1.5%, w/w) as the emulsifier, respectively. The PS emulsion with LCTs exhibited higher viscosity, when compared to the emulsion made by MCT at the same emulsifier concentration, while all emulsions exhibited a shear thinning behavior. The microstructure images revealed that the PS emulsions produced by MCTs and T80 (2.0%, w/w) or WPIs (0.5%, w/w)—T80 (1.5%, w/w) mixed with LCTs can form specific uniform networks, in order to prevent flocculation. After 28 days of storage, no visual phase separation was observed in the emulsions, except for the PS emulsion with the WPI (2.0%, w/w). It was concluded that the characteristics of the interfacial layer of particles in the PS emulsion system were not only dependent on the proportion of the applied emulsifiers, but also dependent on the oily phase features. These findings may provide indications for choosing the suitable process parameters when a stable PS emulsion is produced.

Background: Changes in platelet count (PLT) are strongly associated with patient survival and may be clinically indicative of certain underlying diseases. However, there were few studies on the prognosis of patients with cancer cachexia.

Epilepsy is a chronic neurological disorder that is more prevalent in children, and recurrent unprovoked seizures can lead to cognitive impairment. Numerous studies have reported the benefits of docosahexaenoic acid (DHA) on neurodevelopment and cognitive ability, while comparatively less attention has been given to eicosapentaenoic acid (EPA). Additionally, little is known about the effects and mechanisms of DHA and EPA in relation to seizure-induced cognitive impairment in the young rodent model. Current research indicates that ferroptosis is involved in epilepsy and cognitive deficiency in children. Further investigation is warranted to determine whether EPA or DHA can mitigate seizure-induced cognitive deficits by inhibiting ferroptosis. Therefore, this study was conducted to compare the effects of DHA and EPA on seizure-induced cognitive deficiency and reveal the underlying mechanisms focused on ferroptosis in a pentylenetetrazol (PTZ)-kindling young mice model. Mice were fed a diet containing DHA-enriched ethyl esters or EPA-enriched ethyl esters for 21 days at the age of 3 weeks and treated with PTZ (35 mg/kg, i.p.) every other day 10 times. The findings indicated that both EPA and DHA exhibited ameliorative effects on seizure-induced cognitive impairment, with EPA demonstrating a superior efficacy. Further mechanism study revealed that supplementation of DHA and EPA significantly increased cerebral DHA and EPA levels, balanced neurotransmitters, and inhibited ferroptosis by modulating iron homeostasis and reducing lipid peroxide accumulation in the hippocampus through activating the Nrf2/Sirt3 signal pathway. Notably, EPA exhibited better an advantage in ameliorating iron dyshomeostasis compared to DHA, owing to its stronger upregulation of Sirt3. These results indicate that DHA and EPA can efficaciously alleviate seizure-induced cognitive deficiency by inhibiting ferroptosis in PTZ-kindled young mice.