Antibacterial and in vitro anticancer activities of the antimicrobial peptide NRC-07 encapsulated in chitosan nanoparticles.

Antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics and chemotherapy in the treatment of multidrug-resistant pathogens and drug-resistant cancers. Clinical application of AMPs is limited due to low stability and inefficient transport. Encapsulation in nanocarriers may improve their therapeutic potential. Chitosan nanoparticles (CS-NPs) are efficient carriers for proteins and peptides, improving the treatment of microbial infections and targeted drug delivery. We examined toxicity against cancer cell lines and antibacterial activities of the pleurocidin-like AMP NRC-07 upon encapsulation in CS-NPs by ionotropic gelation. The biological activities of various formulations of free and encapsulated NRC-07 and free nanoparticles were evaluated against Pseudomonas aeruginosa and breast cancer cells, using assays for cell viability and lactate dehydrogenase cytolysis with non-cancer cell lines as controls. NRC-07-containing nanoparticles decreased the bacterial and cancer cell viability in a concentration-dependent manner. Activities of encapsulated peptide were >2-fold higher than those of free NRC-07 peptide. Unloaded CS-NPs and free peptide were not cytotoxic against control cells. Encapsulation of NRC-07 into CS-NPs enhanced the antibacterial and selective cytotoxicity of the peptide, possibly enhancing anticancer activities. Encapsulation presents a promising tool for the development of efficient drug delivery systems.

Association of Thrombospondin-1 (N700S) and Thrombospondin-4 (A387P) Gene Polymorphisms with the Incidence of Acute Myocardial Infarction in Egyptians

BACKGROUND: Thrombospondin (TSP) 1 and 4 are extracellular matrix glycoproteins that me- diate cell proliferation, platelet aggregation and inflammatory response. Conflicting data addressed the possible contribution of TSP-1 and TSP-4 gene polymorphisms to acute myocardial infarction (AMI). OBJECTIVE: Our study aimed to examine the association of TSP-1 (N700S) and TSP-4 (A387P) genetic variants with the incidence of AMI in Egyptians. It also correlated TSP-1 variants to TSP-1 and TNF-α serum concentrations while TSP-4 variants to IL-8 concentration identifying TSPs' contribution to vascular inflammation. METHODS: Genotyping was done in 214 subjects; 114 AMI patients and 100 controls using PCR-RFLP analysis. Serum Tsp-1, TNF-α and IL-8 levels were measured by ELISA assay. RESULTS: For TSP-4, (GC and CC) genotype distribution and the (C) allele frequency were significantly higher in AMI patients than controls (p = 0.0186), (p = 0.0117) respectively. In contrast, TSP-1 genotypes and allele frequencies showed no significant difference between AMI and controls (p = 0.7124 and p = 0.7201, respectively). Serum TSP-1, TNF-α and IL-8 concentrations were significantly elevated in AMI compared to controls (p = 0.0146, p < 0.0001 and p = 0.0057) respectively. Serum IL-8 levels had a significant difference among TSP-4 genotypes (p= 0.0368), being highest in the mutant C allele. Serum TSP-1 and TNF-α concentrations showed no significant difference among TSP-1 genotypes, but there was a positive correlation between both concentrations in AMI patients (p = 0.0014), (r = 0.4125). CONCLUSION: TSP-4 A387P polymorphism, but not TSP-1 polymorphism, is an independent risk factor for AMI in the Egyptians.