Sub-Micrometric Liposomes as Drug Delivery Systems in the Treatment and Periodontitis

Abstract

Periodontitis is a complex disease and bacterial infection is one of the most common factors involved in this disease. Current strategies for the local delivery of antibiotics do not allow a complete clearance of bacteria filling dentinal tubules and this limits their therapeutic efficacy. Therefore, there is a strong need for the development of new delivery strategies aimed at improving the efficacy of antibiotic therapy for periodontitis with special reference to their ability to penetrate into the tubules. The aim of the present study is to develop liposome-based delivery systems of sub-micron dimension, able to diffuse into the dentinal tubules. A further aim of the research is to develop a protocol for enhanced diffusion based on the use of magnetic liposomes and magnetic fields. Liposomes were produced by hydration of a pre-liposomal formulation. The vesicles were stabilised with PEG and their re-sizing was achieved by extrusion. Magnetite nanoparticles were synthesized inside the vesicles, i.e., the chemical reaction involving FeCI 2 , FeCl 3 and NH 3 occurred within the core of the newly formed liposomes. Dynamic Light Scattering analysis was performed for size characterization. A mathematical model was implemented to predict the diffusion ofthe liposomes in dentinal tubules. Ex-vivo validation was performed on extracted human teeth. We produced PEG-ylated liposomes (average size 204.3 nm) and PEG-ylated magnetic liposomes (average size 286 nm) and an iron content of 4.2f1g/ml. Through mathematical modelling, we deduced that sub-micrometer vesicles are able to penetrate into dentinal tubules. This penetration is considerably more effective when the vesicles are magnetized and subjected to an external magnetic field which accelerates their movement within the tubules. The liposome-based delivery systems developed by the present study are able to penetrate deeply into the tubules, sometimes reaching their terminal ends.Periodontitis is a chronic infectious disease of supporting tissue of the teeth (1). As a consequence of bacterial infection, the periodontal tissue becomes inflamed and is slowly destroyed by the inflammatory process. If left untreated, the teeth lose their ligamentous support to the alveolar bone, become loose and are eventually detached (2). In the early phase of the disease (gingivitis),

Polymeric Carriers for Delivery Systems in the Treatment of Chronic Periodontal Disease

“…Di Turp et al have developed liposome-based delivery systems of submicron dimensions which can diffuse into the dentinal tubules [ 107 ]. The liposomes were prepared by hydration of a lyophilized preliposomal formulation consisting of the following components are l- α-phosphatidylcholine β-oleoyl-γ-palmitoyl (POPC), l -α-phosphatidylcholine– d,l -glycerol dioleoyl (PGDO) and cholesterol (CHOL).…”

“…Di Turp et al have developed liposome-based delivery systems of submicron dimensions which can diffuse into the dentinal tubules [107].…”

Novel Bioactive and Therapeutic Dental Polymeric Materials to Inhibit Periodontal Pathogens and Biofilms

“…Meanwhile, they have lower risks of undesirable side effects, superior efficacy and enhanced patient compliance [7]. Due to the relatively low price, higher stability, nontoxicity, biocompatibility, nonimmunogenicity and biodegradability, a variety of polymers are investigated as drug carriers in various formulations and forms such as fibers [38,39,40,41], strips [42], films [43,44], gels [45,46], micro-particles [47,48,49], nanoparticles [11,50,51,52], and vesicular system [53,54]. Table 1 shows various polymer-based local drug delivery systems delivering a variety of antibiotics, such as metronidazole, doxycycline, tetracycline and secnidazole, for combating periodontal pathogens.…”

Advanced drug delivery approaches against periodontitis

“…It was observed that submicrometer magnetized vesicles, subjected to an external magnetic field, were more able to penetrate the tubules since the magnetic field accelerated their movement inside the tubules. Thus this device can provide better clearance of the bacteria from even the deep sites in case of periodontitis (Di Turi et al, 2011). In a recent study Liu and coworkers checked the efficacy of liposome controlledrelease gel containing 2% minocycline hydrochloride in rat periodontitis model.…”