ABSTRACT
The delivery of therapeutic drugs to a specific cellular site is a challenge in the treatment of different diseases. Liposomes have been widely studied as vehicles for drug delivery, and recent research begins to show the potential of the light-controlled opening of liposomes. Liposomes with photoactive molecules can release their cargo upon light irradiation for localized drug release. Light as an external trigger can be controlled temporally and spatially with high precision. In this study, we investigate the potential of light-sensitive liposomes with four photosensitizers and two lipid formulations for light-induced release. To investigate the permeabilization of the liposomes, calcein was encapsulated in high concentration inside the liposomes so that the calcein fluorescence is quenched. If calcein is released from the liposome, quenching is avoided, and the fluorescence increases. We demonstrated that liposomes with the sensitizers benzoporphyrine derivative monoacid (BPD), chlorine e6 (Ce6), Al(III) phthalocyanine chloride disulfonic acid (AlPcS2), and 5,10-di-(4-hydroxyphenyl)-15,20-diphenyl-21,23H-porphyrin (5,10-DiOH) release cargo effectively after irradiation. Liposomes with 5,10-DiOH showed a quicker release compared to the other sensitizers upon irradiation at 420 nm. Further, we observed through fractionated irradiation, that most of the release took place during light application, while the permeability of the liposome decreased shortly after light exposure. This effect was stronger with liposomes containing less cholesterol.
Subject(s)
Delayed-Action Preparations/chemistry , Liposomes/chemistry , Photosensitizing Agents/chemistry , Drug Delivery Systems/methods , Drug Liberation/drug effects , Fluorescence , Indoles/chemistry , Isoindoles , Permeability/drug effects , Porphyrins/chemistryABSTRACT
Magnesium alloys are increasingly researched as temporary biodegradable metal implants in bone applications due to their mechanical properties which are more similar to bone than conventional implant metals and the fact that Magnesium occurs naturally within the body. However, the degradation processes in vivo and in particular the interaction of the bone with the degrading material need to be further investigated. In this study we are presenting the first quantitative comparison of the bone ultrastructure formed at the interface of biodegradable Mg-5Gd and Mg-10Gd implants and titanium and PEEK implants after 4, 8 and 12 weeks healing time using two-dimensional small angle X-ray scattering and X-ray diffraction. Differences in mineralization, orientation and thickness of the hydroxyapatite are assessed. We find statistically significant (p < 0.05) differences for the lattice spacing of the (310)-reflex of hydroxyapatite between titanium and Mg-xGd materials, as well as for the (310) crystal size between titanium and Mg-5Gd, indicating a possible deposition of Mg within the bone matrix. The (310) lattice spacing and crystallite size further differ significantly between implant degradation layer and surrounding bone (p < 0.001 for Mg-10Gd), suggesting apatite formation with significant amounts of Gd and Mg within the degradation layer. STATEMENT OF SIGNIFICANCE: Biodegradable Magnesium-based alloys are emerging as a viable alternative for temporary bone implant applications. However, in order to understand if the degradation of the implant material influences the bone ultrastructure, it is necessary to study the bone structure using high-resolution techniques. We have therefore employed 2D small angle X-ray scattering and X-ray diffraction to study the bone ultrastructure surrounding Magnesium-Gadolinium alloys as well as Titanium and PEEK alloys at three different healing times. This is the first time, that the bone ultrastructure around these materials is directly compared and that a statistical evaluation is performed. We found differences indicating a possible deposition of Mg within the bone matrix as well as a local deposition of Mg and/or Gd at the implant site. DATA AVAILABILITY STATEMENT: The raw/processed data required to reproduce these findings cannot be shared at this time as the data also forms part of an ongoing study.