Angiogenesis is the formation of new blood vessels from pre-existing vessels. It is a highly regulated process as determined by the interplay between pro-angiogenic and anti-angiogenic factors. Under certain conditions the balance between angiogenesis stimulators and inhibitors is altered, which results in a shift from physiological to pathological angiogenesis. Therefore, the goal of therapeutic targeting of angiogenic process is to normalize vasculature in target tissues by enhancing angiogenesis in disease conditions of reduced vascularity and blood flow, such as tissue ischemia, or alternatively to inhibit excessive and abnormal angiogenesis in disorders like cancer. Gold nanoparticles (AuNPs) are special particles that are generated by nanotechnology and composed of an inorganic core containing gold which is encircled by an organic monolayer. The ability of AuNPs to alter vasculature has captured recent attention in medical literature as potential therapeutic agents for the management of pathologic angiogenesis. This review provides an overview of the effects of AuNPs on angiogenesis and the molecular mechanisms and biomedical applications associated with their effects. In addition, the main synthesis methods, physical properties, uptake mechanisms, and toxicity of AuNPs are briefly summarized.

Many recent studies focus on the pulmonary delivery of vaccines as it is needle-free, safe, and effective. Inhaled vaccines enhance systemic and mucosal immunization but still faces many limitations that can be resolved using polymeric nanoparticles (PNPs). This review focuses on the use of properties of PNPs, specifically chitosan and PLGA to be used in the delivery of vaccines by inhalation. It also aims to highlight that PNPs have adjuvant properties by themselves that induce cellular and humeral immunogenicity. Further, different factors influence the behavior of PNP in vivo such as size, morphology, and charge are discussed. Finally, some of the primary challenges facing PNPs are reviewed including formulation instability, reproducibility, device-related factors, patient-related factors, and industrial-level scale-up. Herein, the most important variables of PNPs that shall be defined in any PNPs to be used for pulmonary delivery are defined. Further, this study focuses on the most popular polymers used for this purpose.

Background: Imatinib is mainly metabolized by CYP3A4 and to a lesser extent by other isoenzymes, withN-desmethyl imatinib being its major equipotent metabolite. Being a CYP3A4 substrate, imatinib co-administration with CYP3A4 modulators would change its pharmacokinetic profile. The cancer chemoprevention potential and anticancer efficacy of many herbal products such as grape seed (GS) and green tea (GT) extracts had led to an increase in their concomitant use with anticancer agents. GS and GT extracts were demonstrated to be potent inhibitors of CYP3A4. The aim of this study is to investigate the effect of standardized GS and/or GT extracts at two different doses on the pharmacokinetics of imatinib and its metabolite,N-desmethyl imatinib, in SD-rats.Methods: Standardized GS and/or GT extracts were administered orally once daily for 21 days, at low (l) and high (h) doses, 50 and 100 mg/kg, respectively, before the administration of a single intragastric dose of imatinib. Plasma samples were collected and analyzed for imatinib andN-desmethyl imatinib concentrations using LC-MS/MS method, then their non-compartmental pharmacokinetic parameters were determined.Results: h-GS dose significantly decreased imatinib’s C_maxand the $$ {\mathrm{AUC}}_0^{\infty } $$AUC0∞ by 61.1 and 72.2%, respectively. Similar effects onN-desmethyl imatinib’s exposure were observed as well, in addition to a significant increase in its clearance by 3.7-fold.l-GT caused a significant decrease in imatinib’s C_maxand $$ {\mathrm{AUC}}_0^{\infty } $$AUC0∞ by 53.6 and 63.5%, respectively, with more significant effects onN-desmethyl imatinib’s exposure, which exhibited a significant decrease by 79.2 and 81.1%, respectively.h-GT showed similar effects as those ofl-GT on the kinetics of imatinib and its metabolite. However, when these extracts were co-administered at low doses, no significant effects were shown on the pharmacokinetics of imatinib and its metabolite. Nevertheless, increasing the dose caused a significant decrease in C_maxofN-desmethyl imatinib by 71.5%.Conclusions: These results demonstrated that the pharmacokinetics of imatinib andN-desmethyl imatinib had been significantly affected by GS and/or GT extracts, which could be partially explained by the inhibition of CYP3A-mediated metabolism. However, the involvement of other kinetic pathways such as other isoenzymes, efflux and uptake transporters could be involved and should be characterized.Graphical

Background: Loading Methotrexate, a chemotherapeutic agent, in a nanocarrier can improve its efficacy and lower its side effects. Both PLGA and chitosan were used to formulate Methotrexate nanoparticles. Folate acts as a targeting ligand for anticancer medications. Therefore, folate, chitosan, and PLGA were used to deliver methotrexate. Methods: Folic acid and Chitosan (FA-CS) were conjugated and used to coat Methotrexate-PLGA nanoparticles. The conjugate and the nanoparticles were characterized using Zetasizer to test particle size, polydispersity and charge, SEM was used to test particles’ morphology. Both %EE and %LC of MTX in the NPs were measured. Finally, MTX release and the system cytotoxicity were tested in vitro. Results: FTIR, NMR, and XRD proved the successful formation of FA-CS, and the formation of the coated nanoparticles. The particles were spherical with a size ~385 nm, a disparity ~0.27, and a charge ~+15 mV. The %EE and the % LC were 79% and 21.2%, respectively. In vitro release studies revealed nearly complete MTX release after 48 h. In vitro cytotoxicity testing demonstrated that the formulation components are safe and that the incorporation of MTX within the nanoparticles enhanced the drug’s cytotoxic effect in comparison to the free drug. Conclusion: loading of MTX in the NPs enhances its chemotherapeutic effect, hence, this system can be used to target carcinogenic cells.