The photodynamic (PD) effect has been reported to be efficient for the opening of the blood-brain barrier (BBB), which provides a new informative platform for developing perspective strategies towards brain disease therapy and drug delivery. However, this method is usually performed via craniotomy due to high scattering of the turbid skull. In this work, we employed a newly-developed optical clearing skull window for investigating non-invasive PD-induced BBB opening to high weight molecules and 100-nm fluid-phase liposomes containing ganglioside GM1. The results demonstrated that the BBB permeability to the Evans blue albumin complex is related to laser doses. By in vivo two-photon imaging and ex vivo confocal imaging with specific markers of the BBB, we noticed PD-related extravasation of rhodamine-dextran and liposomes from the vessels into the brain parenchyma. The PD induced an increase in oxidative stress associated with mild hypoxia and changes in the expression of tight junction (CLND-5 and ZO-1) and adherens junction (VE-cadherin) proteins, which might be one of the mechanisms underlying the PD-related BBB opening for liposomes. Our experiments indicate that optical clearing skull window will be a promising tool for non-invasive PD-related BBB opening for high weight molecules and liposomes that provides a novel useful tool for brain drug delivery and treatment of brain diseases.
The review considers liposomes as systems of substantial interest as adjuvant carriers in vaccinology due to their versatility and maximal biocompatibility. Research and development on the use of liposomes and lipid nanoparticles to create subunit vaccines for the prevention and treatment of infectious diseases has been going on for several decades. In recent years, the area has seen serious progress due to the improvement of the technology of industrial production of various high-grade lipids suitable for parenteral administration and the emergence of new technologies and equipment for the production of liposomal preparations. When developing vaccines, it is necessary to take into account how the body's immune system (innate and adaptive immunity) functions. The review briefly describes some of the fundamental mechanisms underlying the mobilization of immunity when encountering an antigen, as well as the influence of liposome carriers on the processes of internalization of antigens by immunocompetent cells and ways of immune response induction. The results of the studies on the interactions of liposomes with antigen-presenting cells in function of the liposome size, charge, and phase state of the bilayer, which depends on the lipid composition, are often contradictory and should be verified in each specific case. The introduction of immunostimulant components into the composition of liposomal vaccine complexes-ligands of the pathogen-associated molecular pattern receptors-permits modulation of the strength and type of the immune response. The review briefly discusses liposomebased vaccines approved for use in the clinic for the treatment and prevention of infectious diseases, including mRNA-loaded lipid nanoparticles. Examples of liposomal vaccines that undergo various stages of clinical trials are presented.
Enzyme-responsive liposomes release their cargo in response to pathologically increased levels of enzymes at the target site. We report herein an assembly of phospholipase A2-responsive liposomes based on colchicinoid lipid prodrugs incorporated into lipid bilayer of the nanosized vesicles. The liposomes were constructed to addresses two important issues: (i) the lipid prodrugs were designed to fit the structure of the enzyme binding site; and (ii) the concept of lateral pressure profile was used to design lipid prodrugs that introduce almost no distortions into the lipid bilayer packing, thus ensuring that corresponding liposomes are stable. The colchicinoid agents exhibit antiproliferative activity in subnanomolar range of concentrations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.