Lectins expressed on the cell surface are often bound and regulated by the membrane molecules containing the glycan ligands on the same cell (cis-ligands). However, molecular nature and function of cis-ligands are generally poorly understood partly because of weak interaction between lectins and glycan ligands. Cis-ligands are most extensively studied in CD22 (also known as Siglec-2), an inhibitory B lymphocyte receptor specifically recognizing a2,6 sialic acids. CD22, CD45 and IgM are suggested to be ligands of CD22. Here we labeled molecules in the proximity of CD22 in situ on B cell surface using biotin-tyramide. Molecules including CD22, CD45 and IgM were labeled in wild-type but not ST6GaIIl B cells that lack 2,6 sialic acids, indicating that these molecules associate with CD22 by lectin-glycan interaction, and are therefore cis-ligands. In ST6GaIIl B cells, these cis-ligands are located in a slightly more distance from CD22. Thus, the lectin-glycan interaction recruits cis-ligands already located in the relative proximity of CD22 through non-lectin-glycan interaction to the close proximity. Moreover, cis-ligands are labeled in Cmahl B cells that lack Neu5Gc preferred by mouse CD22 as efficiently as in wild-type B cells, indicating that very low affinity lectin-glycan interaction is sufficient for recruiting cisligands, and can be detected by proximity labeling. Thus, proximity labeling with tyramide appears to be a useful method to identify cis-ligands and to analyze their interaction with the lectins.

A square wave voltammetric method for selective determination of meropenem (MRP) and ertapenem (ERP) was developed using pencil graphite electrode modified with poly (bromocresol green) (PGE/PBCG). The modified electrode film was characterized by scanning electron microscopy and electro-chemical impedance spectroscopy. Under the optimized conditions, the prepared electrode has good linearity over concentration range 1.0–60.0 and 0.3.0–75.0 μM for MRP and ERP, respectively. The developed method was validated according to ICH guidelines. In addition, the diffusion co-efficients of MRP and ERP were estimated to be 1.24×10−6 and 9.09×10−6 cm2 s−1, respectively using chronoamperometric technique. The developed method was highly sensitive and selective for the determination of MRP or ERP in the presence of their corresponding open beta-lactam ring degradation products. Consequently, it was successfully utilized for in-vitro and in-vivo applications in spiked and real plasma samples of healthy rabbits for their pharmacokinetic studies. Furthermore, the method was applied for the assay of the available dosage forms of both drugs.

A square wave voltammetric method for selective determination of meropenem (MRP) and ertapenem (ERP) was developed using pencil graphite electrode modified with poly (bromocresol green) (PGE/PBCG). The modified electrode film was characterized by scanning electron microscopy and electro-chemical impedance spectroscopy. Under the optimized conditions, the prepared electrode has good linearity over concentration range 1.0–60.0 and 0.3.0–75.0 μM for MRP and ERP, respectively. The developed method was validated according to ICH guidelines. In addition, the diffusion co-efficients of MRP and ERP were estimated to be 1.24×10−6 and 9.09×10−6 cm2 s−1, respectively using chronoamperometric technique. The developed method was highly sensitive and selective for the determination of MRP or ERP in the presence of their corresponding open beta-lactam ring degradation products. Consequently, it was successfully utilized for in-vitro and in-vivo applications in spiked and real plasma samples of healthy rabbits for their pharmacokinetic studies. Furthermore, the method was applied for the assay of the available dosage forms of both drugs.

A square wave voltammetric method for selective determination of meropenem (MRP) and ertapenem (ERP) was developed using pencil graphite electrode modified with poly (bromocresol green) (PGE/PBCG). The modified electrode film was characterized by scanning electron microscopy and electro-chemical impedance spectroscopy. Under the optimized conditions, the prepared electrode has good linearity over concentration range 1.0–60.0 and 0.3.0–75.0 μM for MRP and ERP, respectively. The developed method was validated according to ICH guidelines. In addition, the diffusion co-efficients of MRP and ERP were estimated to be 1.24×10−6 and 9.09×10−6 cm2 s−1, respectively using chronoamperometric technique. The developed method was highly sensitive and selective for the determination of MRP or ERP in the presence of their corresponding open beta-lactam ring degradation products. Consequently, it was successfully utilized for in-vitro and in-vivo applications in spiked and real plasma samples of healthy rabbits for their pharmacokinetic studies. Furthermore, the method was applied for the assay of the available dosage forms of both drugs.

A square wave voltammetric method for selective determination of meropenem (MRP) and ertapenem (ERP) was developed using pencil graphite electrode modified with poly (bromocresol green) (PGE/PBCG). The modified electrode film was characterized by scanning electron microscopy and electro-chemical impedance spectroscopy. Under the optimized conditions, the prepared electrode has good linearity over concentration range 1.0–60.0 and 0.3.0–75.0 μM for MRP and ERP, respectively. The developed method was validated according to ICH guidelines. In addition, the diffusion co-efficients of MRP and ERP were estimated to be 1.24×10−6 and 9.09×10−6 cm2 s−1, respectively using chronoamperometric technique. The developed method was highly sensitive and selective for the determination of MRP or ERP in the presence of their corresponding open beta-lactam ring degradation products. Consequently, it was successfully utilized for in-vitro and in-vivo applications in spiked and real plasma samples of healthy rabbits for their pharmacokinetic studies. Furthermore, the method was applied for the assay of the available dosage forms of both drugs.

Terbium based cyclic voltammetric (CV) method was developed for analysis of imipenem (IMP) using pencil graphite electrode (PGE). Firstly, complexation process was confirmed and evaluated via spectrofluorimetric approach. Then CV method was developed for the determination of IMP for the first time. The oxidation peak current was found to be linear in the range of 15–70 μM. The limits of detection and quantitation (LOD and LOQ) were found to be 2.44× 10−6 and 7.41× 10−6 M, respectively. The methodwas validated according to ICH guidelines. Furthermore, the method was applied successfully for the analysis of intact IMP in presence of either its potential hydrolytic degradation products or concomitantly administrated cilastatin. The proposed method was also applied successfully to bulk powder, dosage forms and biological samples.

Terbium based cyclic voltammetric (CV) method was developed for analysis of imipenem (IMP) using pencil graphite electrode (PGE). Firstly, complexation process was confirmed and evaluated via spectrofluorimetric approach. Then CV method was developed for the determination of IMP for the first time. The oxidation peak current was found to be linear in the range of 15–70 μM. The limits of detection and quantitation (LOD and LOQ) were found to be 2.44× 10−6 and 7.41× 10−6 M, respectively. The methodwas validated according to ICH guidelines. Furthermore, the method was applied successfully for the analysis of intact IMP in presence of either its potential hydrolytic degradation products or concomitantly administrated cilastatin. The proposed method was also applied successfully to bulk powder, dosage forms and biological samples.

Terbium based cyclic voltammetric (CV) method was developed for analysis of imipenem (IMP) using pencil graphite electrode (PGE). Firstly, complexation process was confirmed and evaluated via spectrofluorimetric approach. Then CV method was developed for the determination of IMP for the first time. The oxidation peak current was found to be linear in the range of 15–70 μM. The limits of detection and quantitation (LOD and LOQ) were found to be 2.44× 10−6 and 7.41× 10−6 M, respectively. The methodwas validated according to ICH guidelines. Furthermore, the method was applied successfully for the analysis of intact IMP in presence of either its potential hydrolytic degradation products or concomitantly administrated cilastatin. The proposed method was also applied successfully to bulk powder, dosage forms and biological samples.

Terbium based cyclic voltammetric (CV) method was developed for analysis of imipenem (IMP) using pencil graphite electrode (PGE). Firstly, complexation process was confirmed and evaluated via spectrofluorimetric approach. Then CV method was developed for the determination of IMP for the first time. The oxidation peak current was found to be linear in the range of 15–70 μM. The limits of detection and quantitation (LOD and LOQ) were found to be 2.44× 10−6 and 7.41× 10−6 M, respectively. The methodwas validated according to ICH guidelines. Furthermore, the method was applied successfully for the analysis of intact IMP in presence of either its potential hydrolytic degradation products or concomitantly administrated cilastatin. The proposed method was also applied successfully to bulk powder, dosage forms and biological samples.

Hepatocellular carcinoma (HCC) is the 5th most common cancer type and one of the most aggressive tumors with poor recovery rates. Sorafenib (SOR) is a potent multiple kinase inhibitor drug assigned by FDA as the drug of choice for resistant HCC. Midkine (MK) is a heparin-binding cytokine known to be overexpressed in several malignant tumors with mitogenic, angiogenic, anti-apoptotic and chemo-resistant functions. The aim of the current study was to design a nano-sized lipid-based co-delivery system encapsulating both SOR and a small interfering RNA (siRNA) against MK gene to create a synergistic formulation for maximal efficacy. Various lipids were screened and the highest efficiency was obtained with YSK05, a novel pH-sensitive lipid synthesized in our laboratory. Cell viability studies confirmed synergism between SOR and MK-siRNA with efficient gene silencing as demonstrated by quantitative real time polymerase chain reaction (qRT-PCR) studies. Optimization of different formulation variables created an efficient system with minimum carrier’s toxicity. To improve system’s specificity towards HCC, the system was decorated with a novel targeting ligand exclusive for HCC, namely SP94 peptide, and further optimization has been carried out to balance efficiency and specificity. The system was tested on HCC cell line, HepG2, versus normal hepatocytes, FL83B. Cellular uptake studies by flow cytometry indicated a significant difference between HCC and normal hepatocytes in the uptake of the optimized system proving system’s selectivity for HCC. Cell viability data confirmed the high efficiency and specificity of the optimized system in HCC cells with a minimum effect on normal hepatocytes. The current data are promising and will be extrapolated to the in vivo level in the future.