Nanofiber Polyplex Formation Based on the Morphology Elongation by the Intrapolyplex PEG Crowding Effect

We prepared a multiarm poly­(ethylene glycol)-poly­(l-lysine) block copolymer (maPEG-PLL) with a size-controllable maPEG head and a cationic PLL tail for the evaluation of the effect of maPEG crowding to the polyplex formation with plasmid DNA. maPEG-PLLs of various compositions were synthesized and the formation of a polyplex was confirmed by gel retardation assay. The maPEG-PLL exhibited noncooperative polyplex formation behavior, suggesting the effective hydration of the polyplex. Also, an increase in the size of the maPEG head induces the elongation of polyplex morphology from spherical aggregates to nanorods and nanofibers because of the intrapolyplex PEG crowding effect. Furthermore, an increase in the size of the maPEG head also improves the effective inhibition of the decrease in cell-free gene expression, indicating the importance of the control of pDNA packaging in the polyplex

Sequence variability and candidate gene analysis in two cancer patients with complex clinical outcomes during morphine therapy. Drug Metab Dispos 2003;31: 677–80

This article is available online at http://dmd.aspetjournals.org ABSTRACT: In this case report, we present genetic differences in two morphine-related gene sequences, UDP-glucuronosyltransferase 2B7 (UGT2B7) and opioid receptors (MOR1), in two cancer patients whose clinical responses to morphine were very different [i.e., sensitive (patient 1) and low responder (patient 2)]. In addition, allelic variants in the UGT2B7 gene were analyzed in 46 Japanese individuals. Amplified DNA fragments for the two genes of interest were screened using single strand conformation polymorphism and then sequenced. In the UGT2B7 gene, 12 single nucleotide polymorphisms (SNPs) were newly identified with an allelic frequency ranging from 0.022 to 0.978. Six SNPs in the promoter region (A-1302G, T-1295C, T-1111C, G-899A, A-327G, and T-125C) and two coding SNPs (UGT2B7*2 in exon 2 and C1059G in exon 4) appeared to be consistently linked. Remarkable differences in the nucleotide sequence of UGT2B7 were observed between the two patients; in contrast to patient 1 who had "reference" alleles at almost SNP positions, but a rare ATTGAT*2(AT)C haplotype as homozygosity, patient 2 was a homozygous carrier for the predominant GCCAGC*1(TC)G sequence. Serum morphine and two glucuronide concentrations in patient 2 suggest that the predominant GCCAGC*1G sequence was not associated with a "poor metabolizer" phenotype. In the MOR1 gene, patient 1 had no SNPs, whereas patient 2 was a heterozygous carrier for both the G-1784A and A118G alleles. The present study describes substantial differences in genotype patterns of two genes of interest between the two patients. The results necessitate larger trials to confirm these observations in larger case control studies