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This study aimed to develop a novel pH-modified nanoparticle with improved solubility and oral bioavailability of poorly water-soluble celecoxib by modifying the microenvironmental pH. After assessing the impact of hydrophilic polymers, surfactants and alkaline pH modifiers on the drug solubility, copovidone, sodium lauryl sulfate (SLS) and meglumine were chosen. The optimal formulation of solvent-evaporated, surface-attached and pH-modified nanoparticles composed of celecoxib/copovidone/SLS/meglumine at weight ratios of 1:1:0.2:0, 1:0.375:1.125:0 and 1:1:1:0.2:0.02, respectively, were manufactured using spray drying technique. Their physicochemical characteristics, solubility, dissolution and pharmacokinetics in rats were evaluated compared to the celecoxib powder. The solvent-evaporated and pH-modified nanoparticles converted a crystalline to an amorphous drug, resulting in a spherical shape with a reduced particle size compared to celecoxib powder. However, the surface-attached nanoparticles with insignificant particle size exhibited the unchangeable crystalline drug. All of them gave significantly higher solubility, dissolution, and oral bioavailability than celecoxib powder. Among them, the pH-modified nanoparticles demonstrated the most significant improvement in solubility (approximately 1600-fold) and oral bioavailability (approximately 4-fold) compared to the drug powder owing to the alkaline microenvironment formation effect of meglumine and the conversion to the amorphous drug. Thus, the pH-modified nanoparticle system would be a promising strategy for improving the solubility and oral bioavailability of poorly water-soluble and weakly acidic celecoxib., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The purpose of the present study was to develop hydroxypropyl-β-cyclodextrin (HP-β-CD)-based solid dispersed granules as a superior system to solid dispersion. The solid dispersed granules and solid dispersion were compared in terms of powder property improvement, solubility increment and oral bioavailability enhancement of poorly water-soluble dexibuprofen. Solid dispersion (drug/HP-β-CD/Tween80 = 1:7:0.1, weight ratio) and solid dispersed granules (drug/HP-β-CD/Tween80/Microcrystalline cellulose = 1:7:0.1:4) were fabricated using a spray-dryer and fluid bed granulator, respectively. The HP-β-CD-based solid dispersed granules significantly improved solubility, dissolution profile and oral bioavailability of dexibuprofen compared to pure drug powder. Moreover, the solid dispersed granules maximised the oral bioavailability of dexibuprofen to the same extent as the solid dispersion. However, considerable improvements of powder and tablet properties were observed in solid dispersed granules as compared with solid dispersion. Therefore, HP-β-CD-based solid dispersed granules would be a prospective alternative to solid dispersion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Genetic polymorphisms may affect the molecular mechanisms underlying determination of skin type. So far, several genetic studies have been reported; however, very few studies have been conducted to examine the relationship between genotype and skin phenotypes. In this study, the genome sequences of individuals tested for five cosmetic characteristics (wrinkles, moisture content, pigmentation, oil content, and ensitivity) were determined, and we also conducted five genome-wide association studies (GWASs) to identify predictive markers. Some single-nucleotide polymorphisms (SNPs) within those genes were more frequent in individuals exhibiting stronger traits. GWASs revealed that two genome-wide significant SNPs within FCRL5 and OCA2 genes were associated with wrinkles and pigmentation, respectively (p < 5 × 10 -8 ), and that genomewide SNPs in 21 genes (wrinkles: FCRL5 , REEP3 , ADSS , and SPTLC1 ; moisture: TBX4 , TRPM3 , CEMIP2 , CTSH , and TTC39C ; pigmentation: OCA2 , NCLN , TNS1 , CDC42BPA , HS3ST4 , and UNCX ; oil: SYN2 , CNDP1 , GAS6 , INSR , and TNFRSF19 ; and sensitivity: CREB5 ) might be associated with five skin phenotypes. Among these, a genome-wide significant SNP (rs117381658) and the SNP located downstream of FCRL5 , which encodes a member of the immunoglobulin receptor family, were associated with an increased risk of wrinkles (p = 1.52 × 10 -8 ). The other genome-wide significant SNP (rs74653330) was associated with a decreased risk of pigmentation (p = 1.04 × 10 -8 ), which is located in the coding region of OCA2 that encodes for a transporter of melanin. Our study reports genetic factors associated with skin cosmetology parameters in the Korean population. We hope our findings will provide a foundation for further genetic and molecular studies related to custom cosmetics. Based on these findings, the industry will be able to provide consumers with ingredients capable of palliating the lack of function associated in genes with SNPs.

To develop a novel celecoxib (CXB)-loaded drug delivery system, numerous nanosuspensions were prepared with various polymers and surfactants using a wet media milling process, and their particle sizes were subsequently determined. A 24 full factorial design was used to identify the most appropriate preparation conditions. Pharmacokinetics of the selected nanosuspension were performed in rats and compared with those of a drug powder and a commercial CXB-loaded product. Among the carriers investigated, copovidone and sodium lauryl sulphate gave the smallest particle size of the drug in the nanosuspension. In particular, the nanosuspension prepared with 5% CXB, 4% copovidone, and 0.1% sodium lauryl sulphate, under the appropriate conditions, showed a particle size of approximately 190 nm, which was physically stable for at least 8 weeks. This nanosuspension provided a significantly higher plasma concentration and AUC in rats as compared with the drug powder and the commercial product. Thus, this novel CXB-loaded nanosuspension is a promising candidate with excellent stability and enhanced oral bioavailability.

meso-to-meso 2,5-Pyrrolylene bridged zig-zag porphyrin arrays have been synthesized via a stepwise Suzuki-Miyaura cross coupling reaction. Both the dimeric and trimeric structures of Zn II porphyrin were confirmed by X-ray diffraction analysis. DFT calculations indicate that the porphyrin oligomers are all in zig-zag conformations. The UV/Vis absorption and emission spectra of these porphyrin oligomers were red-shifted as the number of their porphyrin units increased.

In this study, a transferrin-anchored albumin nanoplatform with PEGylated lipid bilayers (Tf-L-APVN) was developed for the targeted co-delivery of paclitaxel and vorinostat in solid tumors. Tf-L-APVN exhibited a sequential and controlled release profile of paclitaxel and vorinostat, with an accelerated release pattern at acidic pH. At cellular levels, Tf-L-APVN significantly enhanced the synergistic effects of paclitaxel and vorinostat on the proliferation of MCF-7, MDA-MB-231, and HepG2 cancer cells. Vorinostat could significantly enhance the cytotoxic potential of paclitaxel, induce marked cell apoptosis, alter cell cycle patterns, and inhibit the migratory capacity of cancer cells. In addition, Tf-L-APVN showed prolonged circulation in the blood and maintained an effective ratio of 1:1 (for paclitaxel and vorinostat) throughout the study period. In HepG2 tumor-bearing mice, Tf-L-APVN displayed excellent antitumor efficacy and the combination of paclitaxel and vorinostat significantly inhibited the tumor growth. Taken together, dual drug-loaded Tf receptor-targeted nanomedicine holds great potential in chemotherapy of solid tumors.

Recently, University of Pittsburgh Medical Center (UPMC) Cancer Centers has installed an Emergency Department Notification System (EDNS) in one of its hospitals. This system, manufactured by Thermo Fisher Scientific (Thermo Fisher Scientific, Inc., 81 Wyman Street, Waltham, MA 02454), was designed to discriminate non-medical radioactive isotopes from medical radioactive isotopes routinely used in nuclear medicine and radiation treatments. It is modular in nature and consists of four NaI(Tl) scintillation detectors, a 512 channels multi-channel analyzer, a system controller, and a database-monitoring server. A series of tests were carried out to evaluate the performance characteristics of this system using a variety of radioactive sources of varying activities. These included measurements of minimum detectable activity, detector response distance to various source activities, detector response to different speeds of a moving radioisotope, and single and multiple radioisotope identification and classification. Measured results show that the system is capable of identifying radioactive sources of nominal activity 0.13 MBq (3.5 μCi) and higher in a relatively short period of time (<11.1 s). The database-monitoring server could send an alarm signal to appropriate personnel when the analysis of the results indicated the presence of a non-medical or threat radioisotope. The present paper reports these results.