Synthesis of Triphenylphosphonium Phospholipid Conjugates for the Preparation of Mitochondriotropic Liposomes.

Surface modification of liposomes with a ligand is facilitated by the conjugation of the ligand to a hydrophobic molecule that serves to anchor the ligand to the liposomal bilayer. We describe here a simple protocol to conjugate a triphenylphosphonium group to several commercially available functionalized phospholipids. The resulting triphenylphosphonium-conjugated lipids can be used to prepare liposomes that preferentially associate with mitochondria when exposed to live mammalian cells in culture.

Survival of Del17p CLL Depends on Genomic Complexity and Somatic Mutation.

Purpose: Chronic lymphocytic leukemia (CLL) with 17p deletion typically progresses quickly and is refractory to most conventional therapies. However, some del(17p) patients do not progress for years, suggesting that del(17p) is not the only driving event in CLL progression. We hypothesize that other concomitant genetic abnormalities underlie the clinical heterogeneity of del(17p) CLL.

Hydrophobized triphenyl phosphonium derivatives for the preparation of mitochondriotropic liposomes: choice of hydrophobic anchor influences cytotoxicity but not mitochondriotropic effect.

Context: Nanocarrier-based strategies to achieve delivery of bioactives specifically to the mitochondria are being increasingly explored due to the importance of mitochondria in critical cellular processes.

Objective: To test the ability of liposomes modified with newly synthesized triphenylphosphonium (TPP)-phospholipid conjugates and to test their use in overcoming the cytotoxicity of stearyl triphenylphosphonium (STPP)-modified liposomes when used for delivery of therapeutic molecules to the mitochondria.

Methods: TPP-phospholipid conjugates with the dioleoyl, dimyristoyl or dipalmitoyl lipid moieties were synthesized and liposomes were prepared with these conjugates in a 1 mol% ratio.

Synthesis of triphenylphosphonium phospholipid conjugates for the preparation of mitochondriotropic liposomes.

Surface modification of liposomes with a ligand is facilitated by the conjugation of the ligand to a hydrophobic molecule that serves to anchor the ligand to the liposomal bilayer. We describe here a simple protocol to conjugate a triphenylphosphonium group to several commercially available functionalized phospholipids. The resulting triphenylphosphonium conjugated lipids can be used to prepare liposomes that preferentially associate with mitochondria when exposed to live mammalian cells in culture.

3D tumor models: history, advances and future perspectives.

Evaluation of cancer therapeutics by utilizing 3D tumor models, before clinical studies, could be more advantageous than conventional 2D tumor models (monolayer cultures). The 3D systems mimic the tumor microenvironment more closely than 2D systems. The following review discusses the various 3D tumor models present today with the advantages and limitations of each.

Ion Exchange Resins Transforming Drug Delivery Systems.

Ion-exchange resins are light, porous, three-dimensional high molecular weight cross - linked matrix of hydrocarbon chains carrying positively or negatively charged sites that can attract an ion of opposite charge from the surrounding medium. There is stoichiometric exchange of mobile ions between the solid and the solution called as Ion-exchange which does not lead to any radical change in the properties and structure of the solid. Depending upon the type of Ionexchanged it can be either Cation-exchange or Anion-exchange.