Combined field and laboratory evaluation of a long-term impregnated bednet, PermaNet.

For how long does the insecticidal effect of long-lasting nets achieve high Anopheles mortality? Four PermaNets tested previously in Colombia for wash resistance were bioassayed again after 3 years of use and 23 washes. The tests were done both in Colombia and a reference laboratory in Indonesia. Additionally the residual concentration of deltamethrin on the nets was chemically analysed. The results showed high Anopheles mortality and a mean deltamethrin concentration of 9.6 mg/m2. Discrepancies with other studies are discussed.

Strength of conjugate binding to plasmid DNA affects degradation rate and expression level in vivo.

In vitro assays have demonstrated the capability of poly-L-lysine to protect plasmid DNA from serum nucleases and cellular lysates. Our purpose was to evaluate the stability and potency of poly-L-lysine-DNA polyplexes after intravenous injection into mice. Polyplexes consisted of 32P-radiolabeled plasmid DNA complexed with poly-L-lysine at specified charge ratios. Variations in conjugate hydrophobicity and levels of modification with polyethylene glycol were investigated. Our results show that, in contrast to in vitro studies, the systemically administered polyplexes exhibited marked DNA degradation in the vascular compartment within 5 min. Substitution of poly-L-lysine epsilon-amino sites with polyethylene glycol or hydrocarbon chains resulted in faster degradation even when complexed at higher charge (+/-) ratios. Use of excess cationic charge in the polyplexes (+/- 2.5) diminished degradation rates only slightly. An analysis was made of the strength of the poly-L-lysine:DNA interaction by competition with poly-aspartic acid. Polyplexes with the strongest binding between conjugate and DNA in the competition assay were also the most stable in blood. However, tighter binding was not enough to fully protect the polyplex in vivo and polyplex DNA was substantially degraded within 10 min. Increased polyplex stability did not correlate with improved in vivo transfection efficiency.