Drug Release by Direct Jump from Poly(ethylene-glycol-b-ε-caprolactone) Nano-Vector to Cell Membrane.

Drug delivery by nanovectors involves numerous processes, one of the most important being its release from the carrier. This point still remains unclear. The current work focuses on this point using poly(ethyleneglycol-b-ε-caprolactone) micelles containing either pheophorbide-a (Pheo-a) as a fluorescent probe and a phototoxic agent or fluorescent copolymers.

Randomised comparison of a bioresorbable everolimus-eluting scaffold with a metallic everolimus-eluting stent for ischaemic heart disease caused by de novo native coronary artery lesions: the 2-year clinical outcomes of the ABSORB II trial.

Aims: The one-year randomised data of the ABSORB II trial showed that the everolimus-eluting bioresorbable scaffold and the everolimus-eluting metallic stent were comparable for the composite secondary clinical outcomes of patient-oriented composite endpoint (PoCE) and device-oriented composite endpoint (DoCE)/target lesion failure (TLF), MACE and TVF. This report describes the two-year clinical outcomes of the ABSORB II trial.

Methods And Results: Patients were randomly assigned in a 2:1 ratio to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb; Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (XIENCE; Abbott Vascular).

A Polylactide Bioresorbable Scaffold Eluting Everolimus for Treatment of Coronary Stenosis: 5-Year Follow-Up.

Background: Long-term benefits of coronary stenosis treatment with an everolimus-eluting bioresorbable scaffold are unknown.

Objectives: This study sought to evaluate clinical and imaging outcomes 5 years after bioresorbable scaffold implantation.

Methods: In the ABSORB multicenter, single-arm trial, 45 (B1) and 56 patients (B2) underwent coronary angiography, intravascular ultrasound (IVUS), and optical coherence tomography (OCT) at different times.

Incidence and Potential Mechanism(s) of Post-Procedural Rise of Cardiac Biomarker in Patients With Coronary Artery Narrowing After Implantation of an Everolimus-Eluting Bioresorbable Vascular Scaffold or Everolimus-Eluting Metallic Stent.

Objectives: This study sought to evaluate the mechanism of post-procedural cardiac biomarker (CB) rise following device implantation.

Background: A fully bioresorbable Absorb scaffold, compared with everolimus-eluting metallic stents (EES), might be associated with a higher incidence of periprocedural myocardial injury.

Methods: In 501 patients with stable or unstable angina randomized to either Absorb (335 patients) or EES (n = 166) in the ABSORB II trial, 3 types of CB (creatine kinase, creatine kinase-myocardial band, and troponin) were obtained before and after procedure.

A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial.

Background: Despite rapid dissemination of an everolimus-eluting bioresorbable scaffold for treatment for coronary artery disease, no data from comparisons with its metallic stent counterpart are available. In a randomised controlled trial we aimed to compare an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent. Here we report secondary clinical and procedural outcomes after 1 year of follow-up.

Shock waves associated with electric pulses affect cell electro-permeabilization.

New features of cell electro-permeabilization are obtained by using high field (several tens of kV/cm) with short (sub-microsecond, nanosecond) pulse duration. Arcing appears as a main safety problem when air gaps are present between electrodes. A new applicator design was chosen to obtain a closed chamber where high field pulses could be delivered in a safe way with very short pulse duration.

Antitumor drug delivery in multicellular spheroids by electropermeabilization.

Electrochemotherapy (ECT) is a physical technique that allows cytotoxic molecules to be efficiently released in tumor cells by inducing transient cell plasma membrane permeabilization. The main antitumoral drugs used in ECT are nonpermeant bleomycin and low permeant cisplatin. The method is nowadays applied in clinics as a palliative treatment.

Investigating relationship between transfection and permeabilization by the electric field and/or the Pluronic® L64 in vitro and in vivo.

Background: Electrotransfer can be obtained by the successive delivery of a high voltage short duration pulse (HV) inducing membrane destabilization and then a low voltage long duration pulse (LV), allowing DNA electrophoresis (HVLV mode). Pluronic® L64 (L64) (Fluka, Sigma-Aldrich, L'Isle-d'Abeau Chesnes, Saint-Quentin Fallavier, France) has permeabilizing properties and amplifies the expression of DNA. We aimed to determine whether L64 could have an adjuvant effect on transfection by electrotransfer and whether the sequence L64 injection and then application of a LV pulse could induce transfection comparable to that observed with the HVLV mode.

Cationic and anionic lipoplexes inhibit gene transfection by electroporation in vivo.

Background: Nonviral gene therapy still suffers from low efficiency. Methods that would lead to higher gene expression level of longer duration would be a major advance in this field. Lipidic vectors and physical methods have been investigated separately, and both induced gene expression improvement.

Gene electrotransfer: from biophysical mechanisms to in vivo applications : Part 1- Biophysical mechanisms.

Electropulsation is one of the nonviral methods successfully used to deliver genes into living cells in vitro and in vivo. This approach shows promise in the field of gene and cellular therapies. The present review focuses on the processes supporting gene electrotransfer in vitro.

Gene electrotransfer: from biophysical mechanisms to in vivo applications : Part 2 - In vivo developments and present clinical applications.

Gene electrotransfer can be obtained not just on single cells in diluted suspension. For more than 10 years, this is a quasi routine strategy in tissue on the living animal and a few clinical trials have now been approved. New problems have been brought by the close contacts of cells in tissue both on the local field distribution and on the access of DNA to target cells.

What is (still not) known of the mechanism by which electroporation mediates gene transfer and expression in cells and tissues.

Cell membranes can be transiently permeabilized under application of electric pulses. This treatment allows hydrophilic therapeutic molecules, such as anticancer drugs and DNA, to enter into cells and tissues. This process, called electropermeabilization or electroporation, has been rapidly developed over the last decade to deliver genes to tissues and organs, but there is a general agreement that very little is known about what is really occurring during membrane electropermeabilization.

Lipoplexes formed from sugar-based gemini surfactants undergo a lamellar-to-micellar phase transition at acidic pH. Evidence for a non-inverted membrane-destabilizing hexagonal phase of lipoplexes.

The present study aims at a better understanding of the mechanism of transfection mediated by two sugar-based gemini surfactants GS1 and GS2. Previously, these gemini surfactants have been shown to be efficient gene vectors for transfection both in vitro and in vivo. Here, using Nile Red, a solvatochromic fluorescent probe, we investigated the phase behavior of these gemini surfactants in complexes with plasmid DNA, so-called lipoplexes.

Cationic lipids, lipoplexes and intracellular delivery of genes.

As a consequence of several setbacks encountered by viral technology in achieving efficient and safe gene therapy in clinical trials, non-viral gene delivery vectors are considered to date as a valuable alternative and to hold promise for future therapeutic applications. Nevertheless, the transfection efficiency mediated by these non-viral gene delivery vectors has to be improved, especially in vivo, to benefit fully from their advantages. Cationic lipid/nucleic acid complexes or lipoplexes have been the subject of intensive investigations in recent years to understand the parameters governing the efficiency of transfection.

Transfection mediated by pH-sensitive sugar-based gemini surfactants; potential for in vivo gene therapy applications.

In this study, the in vitro and in vivo transfection capacity of novel pH-sensitive sugar-based gemini surfactants was investigated. In an aqueous environment at physiological pH, these compounds form bilayer vesicles, but they undergo a lamellar-to-micellar phase transition in the endosomal pH range as a consequence of an increased protonation state. In the same way, lipoplexes made with these amphiphiles exhibit a lamellar morphology at physiological pH and a non-lamellar phase at acidic pH.

Effect of manganese on in vitro replication of damaged DNA catalyzed by the herpes simplex virus type-1 DNA polymerase.

In vitro bypass of damaged DNA by replicative DNA polymerases is usually blocked by helix-distorting or bulky DNA lesions. In this study, we report that substitution of the divalent metal ion Mg2+ with Mn2+ promotes quantitative replication of model DNA substrates containing the major cisplatin or N-2-acetylaminofluorene adducts by the catalytic subunit (UL30) of the replicative DNA polymerase of herpes simplex virus. The ability of Mn2+ ions to confer bypass of bulky lesions was not observed with other replicative DNA polymerases of the B family, such as bacteriophage T4 or delta polymerases.

Interference of poly(ethylene glycol)-lipid analogues with cationic-lipid-mediated delivery of oligonucleotides; role of lipid exchangeability and non-lamellar transitions.

Cationic liposomes are applied to transfer oligonucleotides (ODNs) into cells to regulate gene expression for gene therapeutic or cell biological purposes. In vivo, poly(ethylene glycol) (PEG)-lipid derivatives are employed to stabilize and prolong the circulation lifetime of nucleic acid-containing particles, and to improve targeting strategies. In this study, we have studied the effects of PEG-lipid analogues, i.