Structural properties of plasmenyl-glycerophospholipids (plasmalogens) have been scarcely studied for plasmalogens with long polyunsaturated fatty acid (PUFA) chains, despite of their significance for the organization and functions of the cellular membranes. Elaboration of supramolecular assemblies involving PUFA-chain plasmalogens in nanostructured mixtures with lyotropic lipids may accelerate the development of nanomedicines for certain severe pathologies (e.g., peroxisomal disorders, cardiometabolic impairments, and neurodegenerative Alzheimer's and Parkinson's diseases). Here, we investigate the spontaneous self-assembly of bioinspired, custom-produced docosapentaenoyl (DPA) plasmenyl (ether) and ester phospholipids in aqueous environment (pH 7) by synchrotron small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM). A coexistence of a liquid crystalline primitive cubic Im3m phase and an inverted hexagonal (HII) phase is observed for the DPA-ethanolamine plasmalogen (C16:1p-22:5n6 PE) derivative. A double-diamond cubic Pn3m phase is formed in mixed assemblies of the phosphoethanolamine plasmalogen (C16:1p-22:5n6 PE) and monoolein (MO), whereas a coexistence of cubic and lamellar liquid crystalline phases is established for the DPA-plasmenyl phosphocholine (C16:1p-22:5n6 PC)/MO mixture at ambient temperature. The DPA-diacyl phosphoinositol (22:5n6-22:5n6 PI) ester lipid displays a propensity for a lamellar phase formation. Double membrane vesicles and multilamellar onion topologies with inhomogeneous distribution of interfacial curvature are formed upon incorporation of the phosphoethanolamine plasmalogen (C16:1p-22:5n6 PE) into dioleoylphosphocholine (DOPC) bilayers. Nanoparticulate formulations of plasmalogen-loaded cubosomes, hexosomes, and various multiphase cubosome- and hexosome-derived architectures and mixed type nano-objects (e.g., oil droplet-embedding vesicles or core-shell particles with soft corona) are produced with PUFA-chain phospholipids and lipophilic antioxidant-containing membrane compositions that are characterized by synchrotron SAXS and cryo-TEM imaging. The obtained multiphase nanostructures reflect the changes in the membrane curvature induced by the inclusion of DPA-based PE and PC plasmalogens, as well as DPA-PI ester derivative, and open new opportunities for exploration of these bioinspired nanoassemblies.
- Publikační typ
- časopisecké články MeSH
Sponge-type nanocarriers (spongosomes) are produced upon dispersion of a liquid crystalline sponge phase formed by self-assembly of an amphiphilic lipid in excess aqueous phase. The inner organization of the spongosomes is built-up by randomly ordered bicontinuous lipid membranes and their surfaces are stabilized by alginate chains providing stealth properties and colloidal stability. The present study elaborates spongosomes for improved encapsulation of Brucea javanica oil (BJO), a traditional Chinese medicine that may strongly inhibit proliferation and metastasis of various cancers. The inner structural organization and the morphology characteristics of BJO-loaded nanocarriers at varying quantities of BJO were determined by cryogenic transmission electron microscopy (Cryo-TEM), small angle X-ray scattering (SAXS) and dynamic light scattering (DLS). Additionally, the drug loading and drug release profiles for BJO-loaded spongosome systems also were determined. We found that the sponge-type liquid crystalline lipid membrane organization provides encapsulation efficiency rate of BJO as high as 90%. In vitro cytotoxicity and apoptosis study of BJO spongosome nanoparticles with A549 cells demonstrated enhanced anti-tumor efficiency. These results suggest potential clinical applications of the obtained safe spongosome formulations.
- MeSH
- antitumorózní látky fytogenní aplikace a dávkování chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- Brucea chemie MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nanočástice chemie MeSH
- nosiče léků chemická syntéza chemie MeSH
- oleje aplikace a dávkování chemie farmakologie MeSH
- povrchové vlastnosti MeSH
- proliferace buněk účinky léků MeSH
- velikost částic MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Bioavailability of baicalin (BAI), an example of traditional Chinese medicine, has been modified by loading into liposome. Several liposome systems of different composition i.e., lipid/cholesterol (L), long-circulating stealth liposome (L-PEG) and folate receptor (FR)-targeted liposome (L-FA) have been used as the drug carrier for BAI. The obtained liposomes were around 80 nm in diameter with proper zeta potentials about -25 mV and sufficient physical stability in 3 months. The entrapment efficiency and loading efficiency of BAI in the liposomes were 41.0-46.4% and 8.8-10.0%, respectively. The morphology details of BAI lipsosome systems i.e., formation of small unilamellar vesicles, have been determined by cryogenic transmission electron microscopy (cryo-TEM) and small angle X-ray scattering (SAXS). In vitro cytotoxicity of BAI liposomes against HeLa cells was evaluated by MTT assay. BAI loaded FR-targeted liposomes showed higher cytotoxicity and cellular uptake compared with non-targeted liposomes. The results suggested that L-FA-BAI could enhance anti-tumor efficiency and should be an effective FR-targeted carrier system for BAI delivery.
- MeSH
- antiflogistika nesteroidní chemie farmakokinetika farmakologie MeSH
- difrakce rentgenového záření MeSH
- elektronová kryomikroskopie MeSH
- flavonoidy chemie farmakokinetika farmakologie MeSH
- folátové receptory zakotvené GPI antagonisté a inhibitory metabolismus MeSH
- HeLa buňky MeSH
- konfokální mikroskopie MeSH
- kyselina listová analogy a deriváty chemie MeSH
- lidé MeSH
- liposomy chemie ultrastruktura MeSH
- maloúhlový rozptyl MeSH
- nádory děložního čípku metabolismus patologie MeSH
- polyethylenglykoly chemie MeSH
- stabilita léku MeSH
- transmisní elektronová mikroskopie MeSH
- uvolňování léčiv MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
