Photodynamic therapy (PDT) is an established noninvasive tumor treatment. The hydrophobic natural occurring pigment hypericin shows a lot of attractive properties for the application in PDT. Hence, the administration to biological systems or patients requires the formulation in drug carriers enabling sufficient bioavailability. Therefore, free hypericin was encapsulated by the thin film hydration method or a hypericin-hydroxypropyl-β-cyclodextrin inclusion complex (Hyp-HPβCD) was incorporated by dehydration-rehydration vesicle method in either conventional or ultra-stable tetraether lipid (TEL) liposomes. The hydrodynamic diameter of the prepared nanoformulations ranged between 127 and 212 nm. These results were confirmed by atomic force microscopy. All liposomes showed a good stability under physiological conditions. TEL liposomes which tend to build more rigid bilayers, generate higher encapsulation efficiencies than their conventional counterparts. Furthermore, the suitability for intravenous application was confirmed by hemocompatibility studies resulting in a hemolytic potential less than 20% and a coagulation time less than 50 sec. The uptake of liposomal hypericin into human ovarian carcinoma cells (SK-OV-3) was confirmed using confocal microscopy and further characterized by pathway studies. It was demonstrated that the lipid composition and intraliposomal hypericin localization influenced the anti-vascular effect in the chorioallantoic membrane (CAM). While hypericin TEL liposomes exhibit substantial destruction of the microvasculature drug-in-cyclodextrin TEL liposomes showed no effect. Nevertheless, both formulations yielded severe photocytotoxicity in SK-OV-3 cells in a therapeutic dosage range. Conclusively, hypericin TEL liposomes would be perfectly suited for anti-vascular targeting while Hyp-HPβCD TEL liposomes could deliver the photosensitizer to the tumor site in a more protected manner.
Due to its highly lipophilic nature, poor solubility in aqueous media, and poor bioavailability, the naturally occurring photosensitizer hypericin has a limited therapeutic value. Liposomal encapsulation is a promising solution to overcome these limitations. Use of liposomes as delivery vehicles for hypericin in antimicrobial photodynamic therapy (aPDT) is quite new. The aim of this work is therefore, to prepare various hypericin loaded liposomal formulations viz. DOPE/CHEMS/DPPC, DSPC/DPPC/DSPE-PEG, and DPPC/ DOTAP. The formulations are physicochemically characterized and tested for their binding affinity toward bacteria and for their photodynamic efficiency. All formulations achieve a 2.3-2.5 log reduction of Staphylococcus saprophyticus subsp. bovis and facilitate the binding and uptake of the photosensitizer through the bacterial cell wall.
One of the serious problems occurring after the insertion of implants is the formation of biofilms. This leads to implant loss or sepsis. The multilayer coating developed in this study addresses the problems pertaining to bacterial growth and biofilm formation by two different approaches viz. preventing bacterial adhesion by nanostructured surface modification and by modification of the titanium surface by creating an ultra-thin poly(lactic-coglycolic acid) (PLGA)/norfloxacin (NFX) nanoparticle coating. In this study, NFX loaded PLGA nanoparticles are used to coat titanium surfaces using the layer by layer method alternating with chitosan. The advantages of biodegradable polymers like PLGA and chitosan to create an anti-adhesive and antibacterial coating are utilised. The polymers in this study show a high biocompatibility and are completely degraded within 10 weeks which makes them an excellent choice for use in dental implants and stents.
Polysiloxane and polyurethane are one of the most commonly employed synthetic polymers for medical devices. Both materials are inexpensive and can be modified easily. The layer-by-layer technique is a well-documented method for surface modification. There are only two ways to modify large surface areas i.e. dipping and spraying. Both methods can be used to create anti-adhesive, antibacterial and anti-inflammatory layers. Particle density on the surface is an important parameter for preventing biofilm formation, bacterial adhesion and release of active agents. There should be an optimal number of particles covering the coated surface due to its direct correlation with the release of active agent (per time) and contact area with bacteria. Preliminary studies using regular dipping technique of layer-by-layer method have not produced substantial particle densities. Therefore, spraying method is employed using an atomiser to produce a fine mist containing norfloxacinloaded nanoparticles and liposomes. An optimal density of particles on the implant surface together with a homogeneous distribution is achieved using this method.
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