Experimental design and desirability function approach for development of novel anticancer nanocarrier delivery systems.

The therapeutic effects of anticancer drugs would highly improve if problems with low water solubility and toxic adverse reactions could be solved. In this work, a full factorial experimental design was used to develop a polymeric nanoparticulate delivery system as an alternative technique for anticancer drug delivery. Nanoparticles containing tamoxifen citrate were prepared and characterized using an O/W emulsification-solvent evaporation technique and different analytical methods. Scanning Electron Microscopy (SEM), particle size analysis and High Pressure Liquid Chromatography (HPLC) were used for characterization of nanoparticles. Nanoparticles' characteristics including size, size distribution, drug loading and the efficiency of encapsulation were optimized by means of a full factorial experimental design over the influence of four different independent variables and desirability function using Design-Expert software. The resulting tamoxifen loaded nanoparticles showed the best response with particle sizes less than 200 nm, improved encapsulation efficiency of more than 80% and the optimum loading of above 30%. The overall results demonstrate the implication of desirability functionin experimental design as a beneficial approach in nanoparticle drug delivery design.

The first study of galactose-1-phosphate uridyl transferase mutations in Iranian galactosemia patients.

OBJECTIVES: Classical galactosemia (McKusick 230400) is an autosomal recessive disorder caused by mutations in the galactose-1-phosphate uridyl transferase (GALT;EC 2.7.7.10) gene. DESIGN AND METHODS: In the present study, we report molecular analysis of 14 unrelated Iranian galactosemia children with reduced or without GALT activity using PCR-RFLP and SSCP-Sequencing methods. RESULTS: Q188R mutation was the most observed mutation with the allelic frequency of 57.1%. The allelic frequencies for S135L, Y209S, A320T, and K285N were found to be 7.1%, 7.1%, 7.1%, and 3.57% respectively. CONCLUSIONS: Our results show that galactosemia is a heterogeneous disorder at the molecular level among the Iranian population.

First study of CF mutations in the CFTR gene of Iranian patients: detection of DeltaF508, G542X, W1282X, A120T, R117H, and R347H mutations.

Thirty-seven unrelated Iranian CF families were screened for the presence of seven common mutations (DeltaF508, G542X, W1282X, G551D, N1303K, 1717-1G-->A, and 621-1G-->T) using ARMS PCR and exons 4 and 7 of the CFTR gene by SSCP method. This study resulted in the identification of 26.8 per cent of all CF alleles: DeltaF508 (16.2 per cent), W1282X (4 per cent), G542X (2.7 per cent), R117H (1.3 per cent), R347H (1.3 per cent), and A120T (1.3 per cent) mutations were detected. To the best of our knowledge, it is the first report of an Asian subject carrying the A120T mutation. Our findings suggest heterogeneity in the Iranian population, stressing the need to draw attention to sequence analysis in order to find population-specific mutations.