Chitosan nanoparticles effectively combat salinity stress by enhancing antioxidant activity and alkaloid biosynthesis in Catharanthus roseus (L.) G. Don.

Chitosan nanoparticles (CSNPs) are non-toxic and biodegradable stimulants of growth and secondary metabolite production, which offer new routes to combat plant stress. Salinity is a common and significant abiotic stress that adversely affects plant growth and development. The possible benefits of CSNPs in salt stress mitigation have not yet been reported in Catharanthus roseus, an important source of anticancer alkaloids. Plants were exposed to 150 mM NaCl as a salt stress treatment, while CSNPs were applied as a foliar spray at 1% concentration. Plant growth was considerably impaired under salt stress conditions; however, CSNPs treatment significantly reversed this effect. Specifically, CSNPs retarded chlorophyll reduction and induced activities of catalase, ascorbate peroxidase, and glutathione reductase. Thus, CSNPs alleviated the oxidative stress, indicated by lower levels of malondialdehyde and H2O2, thereby enabling membrane function retention and enhancing salt tolerance. Higher alkaloid accumulation was observed in salt-stressed plants following CSNP spraying than in controls. Interestingly, the expression levels of mitogen-activated protein kinases (MAPK3), geissoschizine synthase (GS), and octadecanoid-derivative responsive AP2-domain (ORCA3) genes were significantly elevated in salt-stressed plants sprayed with CSNPs. Overall, CSNP treatment overcame the deleterious effects of salinity in C. roseus by activating the antioxidant defense system, which helps to scavenge reactive oxygen species, and inducing expression of MAPK3, GS, and ORCA3 genes, thus, leading to higher alkaloid accumulation and better protection against salinity stress.

Characterization and activity of cephalosporin metal complexes.

Semi-synthetic cephalosporin antibiotics have structures similar to that of penicillins, and both groups of compounds are characterized by similar properties and determined by the same methods. Most antibiotics, including cephalosporins and their decomposition products, contain electron donor groups that can bind naturally occurring metal ions in vivo. Cephalosporin antibiotics exhibit a change in their toxicological properties and biological performance when they were tested as metal complexes. The proposed reason for such a behavior is the capability of chelate binding of the cephalosporins to the metals. In an attempt to understand the coordination mode of metals with cephalosporins, different spectroscopic techniques such as IR, UV-visible, NMR spectroscopy and voltammetric measurements were carried out to elucidate the structure of the metal-cephalosporin complexes. Synthesis, characterization and biological screening of the cephalosporins and of the cephalosporin-metal complexes are discussed in this review. However, little information is available on the influence of the metal ions on the pharmacokinetics of the cephalosporin derivatives.

Antitumor effect of liposome-incorporated camptothecin in human malignant xenografts.

The nuclear enzyme topoisomerase I (topo I) has been recently recognized as the target for the anticancer drug camptothecin (CPT; NSC 94600) and its derivatives. This drug has been reported to display effective antitumor effects on a variety of human tumor models xenografted in nude mice. However clinical studies of sodium CPT have revealed that the open-ring form of the drug is a poor inhibitor of topo I and much less potent antitumor agent than CPT lactone. However, the insolubility of CPT lactone makes it difficult to devise a suitable formulation for further clinical testing. In view of these observations, we report here the successful incorporation of CPT into a liposome-based drug delivery system (LCPT) composed of DPPC:Sph:CHOL:PI (2.4:6.6:1.0:0.05 M ratio) that can be used as a suitable formulation for clinical testing of the drug. Higher incorporation efficiency was observed when the total phospholipids:drug ratio = 40 and the cholesterol content = 1%. Image analysis of the CPT-containing liposomes with freeze-fracture electron microscopy has indicated that CPT significantly increased the interlamellar space of the vesicles as a result of its intercalation between lipid bilayers. This has occurred with no major disruptive effects on the bilayer structure. The in vitro drug release study in human serum was characterized by an initial rapid loss-of 50% of contents during 4 h, followed by a slow leakage of the remaining 50% of the total drug over a 20 h period. When tested for its antitumor activity on nude mice xenografted with human malignant melanoma and breast carcinoma, LCPT displayed effective antitumor activity with minimal host toxicity. For example, single i.m. injection of LCPT at 10 mg/kg has produced complete tumor regression to nude mice xenografted with CLO breast carcinoma. Likewise, similar results were obtained with the nude mice xenografted with human malignant BRO cells melanoma. These results appear to suggest that i.m. administration of liposome-incorporated CPT has considerable potential for the treatment of human neoplastic diseases, especially lymph node metastases.