Background and purpose: Niosomes are nonionic surfactant-based vesicles that exhibit certain unique features which make them favorable nanocarriers for sustained drug delivery in cancer therapy. Biodistribution studies are critical in assessing if a nanocarrier system has preferential accumulation in a tumor by enhanced permeability and retention effect. Radiolabeling of nanocarriers with radioisotopes such as Technetium-99m (^99mTc) will allow for the tracking of the nanocarrier noninvasively via nuclear imaging. The purpose of this study was to formulate, characterize, and optimize ^99mTc-labeled niosomes. Methods: Niosomes were prepared from a mixture of sorbitan monostearate 60, cholesterol, and synthesized D-α-tocopherol polyethylene glycol 1000 succinate-diethylenetriaminepentaacetic acid (synthesis confirmed by ¹H and ¹³C nuclear magnetic resonance spectroscopy). Niosomes were radiolabeled by surface chelation with reduced ^99mTc. Parameters affecting the radiolabeling efficiency such as concentration of stannous chloride (SnCl₂·H₂O), pH, and incubation time were evaluated. In vitro stability of radiolabeled niosomes was studied in 0.9% saline and human serum at 37°C for up to 8 hours. Results: Niosomes had an average particle size of 110.2±0.7 nm, polydispersity index of 0.229±0.008, and zeta potential of -64.8±1.2 mV. Experimental data revealed that 30 µg/mL of SnCl₂·H₂O was the optimal concentration of reducing agent required for the radiolabeling process. The pH and incubation time required to obtain high radiolabeling efficiency was pH 5 and 15 minutes, respectively. ^99mTc-labeled niosomes exhibited high radiolabeling efficiency (>90%) and showed good in vitro stability for up to 8 hours. Conclusion: To our knowledge, this is the first study published on the surface chelation of niosomes with ^99mTc. The formulated ^99mTc-labeled niosomes possessed high radiolabeling efficacy, good stability in vitro, and show good promise for potential use in nuclear imaging in the future.

Plants are an important source of drug development and numerous plant derived molecules have been used in clinical practice for the ailment of various diseases. The Toll-like receptor-4 (TLR-4) signaling pathway plays a crucial role in inflammation including rheumatoid arthritis. The TLR-4 binds with pro-inflammatory ligands such as lipopolysaccharide (LPS) to induce the downstream signaling mechanism such as nuclear factor κappa B (NF-κB) and mitogen activated protein kinases (MAPKs). This signaling activation leads to the onset of various diseases including inflammation. In the present study, 22 natural compounds were studied against TLR-4/AP-1 signaling, which is implicated in the inflammatory process using a computational approach. These compounds belong to various classes such as methylxanthine, sesquiterpene lactone, alkaloid, flavone glycosides, lignan, phenolic acid, etc. The compounds exhibited different binding affinities with the TLR-4, JNK, NF-κB, and AP-1 protein due to the formation of multiple hydrophilic and hydrophobic interactions. With TLR-4, rutin had the highest binding energy (−10.4 kcal/mol), poncirin had the highest binding energy (−9.4 kcal/mol) with NF-κB and JNK (−9.5 kcal/mol), respectively, and icariin had the highest binding affinity (−9.1 kcal/mol) with the AP-1 protein. The root means square deviation (RMSD), root mean square fraction (RMSF), and radius of gyration (RoG) for 150 ns were calculated using molecular dynamic simulation (MD simulation) based on rutin’s greatest binding energy with TLR-4. The RMSD, RMSF, and RoG were all within acceptable limits in the MD simulation, and the complex remained stable for 150 ns. Furthermore, these compounds were assessed for the potential toxic effect on various organs such as the liver, heart, genotoxicity, and oral maximum toxic dose. Moreover, the blood–brain barrier permeability and intestinal absorption were also predicted using SwissADME software (Lausanne, Switzerland). These compounds exhibited promising physico-chemical as well as drug-likeness properties. Consequently, these selected compounds portray promising anti-inflammatory and drug-likeness properties.

Recent developments in nucleoside/nucleotide therapeutics and antiviral drug targets are described covering progress in the development of nucleoside/nucleotide mimetics for the treatment of influenza virus, human immunodeficiency virus type 1, hepatitis B and C virus, herpes virus infections; including herpes simplex virus, cytomegalovirus and varicella zoster virus infections, and the highly pathogenic poxviruses (variola, vaccinia and mokey pox) and filoviruses (Ebola and Marburg).

G protein-coupled estrogen receptor-1 (GPER-1) is a seven transmembrane receptor, responsible for mediating rapid estrogen signaling in many physiological responses in reproductive, nervous, endocrine, immune and cardiovascular systems. Due to unavailability of the crystal structure of GPER-1, we have performed sequential ligand-based virtual screening (LBVS) and structure-based screening (SBVS) to identify potential GPER-1 modulators. LBVS and SBVS approaches were validated retrospectively using the Receiver Operating Curve (ROC) plot and the early Enrichment Factor (EF). LBVS was performed based on a GPER-1 agonist, G1, as a query model for screening of the eMolecules library using the Rapid Overlay of Chemical Structure (ROCS) and the electrostatic potential screening (EON) approaches. Top-scored hits from LBVS were further screened by SBVS. SBVS was based on generating homology models of GPER-1 and subsequent molecular docking studies. Using Chemguass4 score, we filtered the final hits with the higher score in comparison to G1 (Chemguass4 score = −11.575). The top-ranked hits were clustered based on similarity in their scaffolds. Prospective validation was performed by evaluating the antiproliferative activity of synthesized compounds (SK0 and SK0P) which were representative of top hits obtained from our virtual screening approach.

Attenuated total reflectance Fourier transform infrared spectrometric method for determination of crocin in commercial saffron samples was studied. Calibration models were built based on the peaks at spectral region of 1700–900 cm⁻¹ and spectral wavenumbers with correlation coefficient (r) greater than 0.99 were selected for quantification of crocin in the samples. The quantitative analysis of samples by attenuated total reflectance Fourier transform infrared was tested against reference UV-visible spectrophotometry method. Considerable correlation (r = 0.95) between both methods in prediction of crocin content among the saffron samples indicated that the proposed methodology has the potential application as a rapid screening tool.