Beitrag zur Lehre von der Korsakoff'schen Psychose mit besonderer Berücksichtigung der pathologischen Anatomie. Ein weiterer Fall

Ohne ZusammenfassungEs ist mir eine angenehme Pflicht an dieser Stelle meinem hochgeehrten Léhrer, Herrn Hofrath Professor Dr. Fürstner für die Anregung zu dieser Arbeit sowie für die Ueberlassung des Falles und Herrn Privatdocent Dr. Rosenfeld für die Unterstützung bei der mikroskopischen Untersuchung bestens zu danken.     

Bioresponsive Deciduous-Charge Amphiphiles for Liposomal Delivery of DNA and siRNA

Purpose

Biolabile cationic lipids were developed for efficient intracellular delivery of DNA and siRNA.

Methods

The compounds have been designed starting from the membrane lipid DOPC in a way they may loose their cationic charge when exposed to an acidic and/or enzymatic stimulus, such as those met during the journey of a lipoplex in biological media.

Results

They demonstrated remarkable efficiency to deliver DNA in various cell lines (BHK-21, Calu-3, NCI-H292, and A549), with no significant cytotoxicity. Furthermore, two of the compounds (carbonate-based DOPC derivatives) revealed able to deliver small interfering RNA in U87Luc and A549Luc cancer cells and to mediate a selective 70–80% knockdown of the stably transfected luciferase gene.

Conclusions

The results show that the described bioresponsive cationic lipids have high DNA and siARN delivery activity which is encouraging in view of delivering a therapeutic nucleic acid to pulmonary tissues in vivo.     

Gelucire-stabilized nanoparticles as a potential DNA delivery system

Clinical viability of gene delivery systems has been greatly impacted by potential toxicity of the delivery systems. Recently, we reported the nanoparticle (NP) preparation process that employs biocompatible materials such as Gelucire® 44/14 and cetyl alcohol as matrix materials. In the current study, the NP preparation was modified for pDNA loading through: (i) inclusion of cationic lipids (DOTAP or DDAB) with NP matrix materials; or (ii) application of cationic surfactants (CTAB) to generate NPs with desired surface charges for pDNA complexation. Colloidal stability and efficiency of loading pGL3-DR4X2-luciferase plasmid DNA in NPs were verified by gel permeation chromatography. Compared to pDNA alone, all the NPs were effective in preserving pDNA from digestion by DNase. While pDNA loading using CTAB-NPs involved fewer steps compared to DOTAP-NPs and DDAB-NPs, CTAB-NPs were greatly impacted by elevated cytotoxicity level which could be ascribed to the concentrations of CTAB in NP formulations. In vitro transfection studies (in HepG2 cells) based on luciferase expression showed the ranking of cell transfection efficiency as DOTAP-NPs?>?DDAB-NPs?>?CTAB-NPs. The overall work provided an initial assessment of gelucire-stabilized NPs as a potential platform for gene delivery.