Revolutionizing Knee Osteoarthritis Treatment: Innovative Self-Nano-Emulsifying Polyethylene Glycol Organogel of Curcumin for Effective Topical Delivery.

In the current study, self-nano-emulsifying (SNE) physically cross-linked polyethylene glycol (PEG) organogel (SNE-POG) as an innovative hybrid system was fabricated for topical delivery of water-insoluble and unstable bioactive compound curcumin (CUR). Response surface methodology (RSM) based on Optimal Design was utilized to evaluate the formulation factors. Solid fiber mechanism with homogenization was used to prepare formulations. Pharmaceutical evaluation including rheological and texture analysis, their mathematical correlations besides physical and chemical stability experiments, DSC study, in vitro release, skin permeation behavior, and clinical evaluation were carried out to characterize and optimize the SNE-OGs. PEG 4000 as the main organogelator, Poloxamer 188 (Plx188) and Ethyl Cellulose (EC) as co-gelator/nanoemulsifier agents, and PEG 400 and glycerin as solvent/co-emulsifier agents could generate SNE-POGs in PS range of 356 to 1410 nm that indicated organic base percentage and PEG 4000 were the most detrimental variables. The optimized OG maintained CUR stable in room and accelerated temperatures and could release CUR sustainably up to 72 h achieving high flux of CUR through guinea pig skin. A double-blind clinical trial confirmed that pain scores, stiffness, and difficulty with physical function were remarkably diminished at the end of 8 weeks compared to the placebo (71.68% vs. 7.03%, 62.40% vs. 21.44%, and 45.54% vs. 8.66%, respectively) indicating very high efficiency of system for treating knee osteoarthritis. SNE-POGs show great potential as a new topical drug delivery system for water-insoluble and unstable drugs like CUR that could offer a safe and effective alternative to conventional topical drug delivery system.

Optically pumped lasing at 3 µm from compositionally graded GeSn with tin up to 22.3.

The recent demonstration of the GeSn laser opened a promising route towards the monolithic integration of light sources on the Si platform. A GeSn laser with higher Sn content is highly desirable to enhance the emission efficiency and to cover longer wavelength. This Letter reports optically pumped edge-emitting GeSn lasers operating at 3 µm, whose device structure featured Sn compositionally graded with a maximum Sn content of 22.3%. By using a 1950-nm laser pumping in comparison with a 1064-nm pumping, the local heating and quantum defect were effectively reduced, which improved laser performance in terms of higher maximum lasing temperature and lower threshold.

Study of a SiGeSn/GeSn/SiGeSn structure toward direct bandgap type-I quantum well for all group-IV optoelectronics.

A SiGeSn/GeSn/SiGeSn single quantum well structure was grown using an industry standard chemical vapor deposition reactor with low-cost commercially available precursors. The material characterization revealed the precisely controlled material growth process. Temperature-dependent photoluminescence spectra were correlated with band structure calculation for a structure accurately determined by high-resolution x-ray diffraction and transmission electron microscopy. Based on the result, a systematic study of SiGeSn and GeSn bandgap energy separation and barrier heights versus material compositions and strain was conducted, leading to a practical design of a type-I direct bandgap quantum well.

Temperature dependent spectral response and detectivity of GeSn photoconductors on silicon for short wave infrared detection.

The GeSn direct gap material system, with Si complementary-metal-oxide semiconductor (CMOS) compatibility, presents a promising solution for direct incorporation of focal plane arrays with short wave infrared detection on Si. A temperature dependence study of GeSn photoconductors with 0.9, 3.2, and 7.0% Sn was conducted using both electrical and optical characterizations from 300 to 77 K. The GeSn layers were grown on Si substrates using a commercially available chemical vapor deposition reactor in a Si CMOS compatible process. Carrier activation energies due to ionization and trap states are extracted from the temperature dependent dark I-V characteristics. The temperature dependent spectral response of each photoconductor was measured, and a maximum long wavelength response to 2.1 µm was observed for the 7.0% Sn sample. The DC responsivity measured at 1.55 µm showed around two orders of magnitude improvement at reduced temperatures for all samples compared to room temperature measurements. The noise current and temperature dependent specific detectivity (D*) were also measured for each sample at 1.55 µm, and a maximum D* value of 1 × 10(9) cm·âˆšHz/W was observed at 77 K.

Design of ultra-fine carvedilol nanococrystals: Development of a safe and stable injectable formulation.

Carvedilol (CAR) is a strategic beta-blocker agent which its application has been limited by its very low water solubility. The present study describes a soluble form of drug based on nano-cocrystal (NCC) anti-solvent precipitation technique. The COSMOquick software was employed to select the optimum coformer (tartaric acid, TA) and organic solvent (acetone) relying on the enthalpy changes of cocrystallization and solubilization. Central Composite Design (CCD) considering the impact of CAR, TA, poloxamer 188 (stabilizer) concentrations, and anti-solvent/solvent ratio on CAR NCCs particle size (PS) could produce ultra-fine NCCs (about 1 nm). The lyophilization of NCCs investigating slow/fast freezing rates, various types and concentrations of cryprotectants and lyoprotectants indicated that PEG and trehalose (5 % w/vconcentration) under slow freezing rate could re-produce the initial PSs successfully. CAR NCCs indicated about 2000 fold increase in solubility compared with pure CAR. DSC and PXRD experiments proved that the formulations containing trehalose led to more crystalline and the ones comprising PEG led to more amorphous structures. Interestingly, the slow freezed PEG protected NCCs were physically stable for at least 18 months. In conclusion, the NCC technology could produce the first safe soluble form of CAR for treating hypertension urgencies easy for industrial scale-up.

Expanding the Biotherapeutics Realm via miR-34a: "Potent Clever Little" Agent in Breast Cancer Therapy.

BACKGROUND: One of the most prevalent cancers befell to women is considered to be breast cancer (BC). It is also the deadliest among the female population after lung cancer. Additionally, several studies have demonstrated that there is an association between microRNA34-a and breast cancer. METHODS: We searched PubMed, Web of Science, and Google Scholar up to December 2018. Those studies which have been studied miR-34a and its tumor-suppressing capabilities were considered as the most important topics. Moreover, we extracted articles which were solely focused on microRNA-34a in breast cancer therapy. Finally, 80 articles were included. RESULTS: In comparison with the normal tissues, down-regulation of miR-34a expression is shown considerably in tumor cells. Overexpression of miR-34a acts as a tumor suppressor by transcriptional regulating one of the signaling pathways (TP53), NOTCH, and transforming growth factor beta (TGF-ß), Bcl- 2 and SIRT1genes, HDAC1 and HDAC7, Fra-1, TPD52, TLR Via CXCL10. Moreover, drug resistance declines which lead to the apoptosis, cell cycle arrest and senescence. As a result, the proliferation, invasion and metastasis of the tumor are suppressed. The Mrx34 drug contains miR-34a mimic and a lipid vector. MiR-34a as the active ingredient portrays the role of a tumor suppressor. This drug has recently entered the clinical trials studies. CONCLUSION: These findings suggest a robust cause for developing miR-34a as a therapeutic agent to target BC. In that scenario, miR-34a is strongly useful to introduce new therapeutic goals for BC. Moreover, this review aims to confirm the signal pathways, therapeutic and diagnostic values of miR- 34a in BC and beyond.

Ge1-xSnx alloys: Consequences of band mixing effects for the evolution of the band gap Γ-character with Sn concentration.

In this work we study the nature of the band gap in GeSn alloys for use in silicon-based lasers. Special attention is paid to Sn-induced band mixing effects. We demonstrate from both experiment and ab-initio theory that the (direct) Γ-character of the GeSn band gap changes continuously with alloy composition and has significant Γ-character even at low (6%) Sn concentrations. The evolution of the Γ-character is due to Sn-induced conduction band mixing effects, in contrast to the sharp indirect-to-direct band gap transition obtained in conventional alloys such as Al1-xGaxAs. Understanding the band mixing effects is critical not only from a fundamental and basic properties viewpoint but also for designing photonic devices with enhanced capabilities utilizing GeSn and related material systems.