Ana Bettencourt

Biodegradation of acrylic based resins: A review

OBJECTIVES The development of different types of materials with application in dentistry is an area of intense growth and research, due to its importance in oral health. Among the different materials there are the acrylic based resins that have been extensively used either in restorations or in dentures. The objective of this manuscript was to review the acrylic based resins biodegradation phenomena. Specific attention was given to the causes and consequences of materials degradation under the oral environment. DATA AND SOURCES Information from scientific full papers, reviews or abstracts published from 1963 to date were included in the review. Published material was searched in dental literature using general and specialist databases, like the PubMED database. STUDY SELECTION Published studies regarding the description of biodegradation mechanisms, in vitro and in vivo release experiments and cell based studies conducted on acrylic based resins or their components were evaluated. Studies related to the effect of biodegradation on the physical and mechanical properties of the materials were also analyzed. CONCLUSIONS Different factors such as saliva characteristics, chewing or thermal and chemical dietary changes may be responsible for the biodegradation of acrylic based resins. Release of potential toxic compounds from the material and change on their physical and mechanical properties are the major consequences of biodegradation. Increasing concern arises from potential toxic effects of biodegradation products under clinical application thus justifying an intensive research in this area.

Daptomycin: A Review of Properties, Clinical Use, Drug Delivery and Resistance

Daptomycin is a branched cyclic anionic lipopeptide antibiotic that was discovered in the early 1980s but got the FDA approval only in 2003. This novel pharmaceutical molecule has demonstrated great in vitro activity against a wide range of aerobic and anaerobic gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Daptomycin has a unique mechanism of action, not completely understood, involving a calcium-dependent dissipation of membrane potential leading to the release of intracellular ions from the cell and bacteria death. This antibiotic has been already approved for the treatment of patients with complicated skin and skin structure infections, right-sided endocarditis and bacteraemia. Local delivery of daptomycin is an emerging area of study. Current in vitro studies show that daptomycin can be eluted from polymethylmethacrylate, calcium sulfate and chitosan films. Emerging cases of resistance to daptomycin have been reported, commonly occurring by spontaneous mutations, and have been associated with prolonged use, osteomyelitis, acute myeloid leukemia and leucocyte adhesion deficiency syndrome. This review examines the most recent literature evidences on daptomycin molecular structure, mechanism of action, bacterial spectrum, clinical uses, local delivery, toxicity and resistance.

Poly(methyl methacrylate) particulate carriers in drug delivery

Poly(methyl methacrylate) (PMMA) is one of the most widely explored biomedical materials because of its biocompatibility, and recent publications have shown an increasing interest in its applications as a drug carrier. PMMA-based particulate carriers (PMMAP) can be prepared either by polymerization methods or from pre-formed polymer-based techniques. Potential biomedical application of these particles includes their use as adjuvant for vaccines and carrier of many drugs as antibiotics and antioxidants via different routes of administration. Release of drugs from PMMAP occurs typically in a biphasic way with an incomplete drug release. To improve release profiles, recent strategies are focusing on increasing polymer hydrophilicity by synthesizing functionalized PMMA microspheres or by formulating PMMA composites with hydrophilic polymers. This review examines the current status of preparation techniques, drug release kinetics, biomedical applications and toxicity of these nano/micro PMMA-based particulate carriers.

In vitro release studies of methylmethacrylate liberation from acrylic cement powder

Bone cement or polymethylmethacrylate (PMMA) is commonly used for anchoring cemented prosthesis to the bone. Cytotoxic effect of culture media exposed to PMMA powder may be related with long term problems associated with acrylic cement application, being the monomer (methylmethacrylate) one of the cements component partly responsible for the cytotoxic effect. The present work reports the studies of monomer release from acrylic bone cement powder under different experimental conditions: setting time of PMMA (in solution and air) and different culture media composition. High-performance liquid chromatography was used for the determination of residual monomer. Mathematical models were applied to experimental dissolution data revealing that monomer release is lightly affected by the studied variables. The monomer release seems to be a surface phenomena, suggesting that the possible actions of monomer will mainly be due to the initial loss of non polymerized monomer rather than to further depolymerization of the already polymerized cement.

A novel modified acrylic bone cement matrix. A step forward on antibiotic delivery against multiresistant bacteria responsible for prosthetic joint infections

Currently the safe and responsible use of antibiotics is a world-wide concern as it promotes prevention of the increasing emergence of multiresistant bacterial strains. Considering that there is a noticeable decline of the available antibiotic pipeline able to combat emerging resistance in serious infection a major concern grows around the prosthetic joint infections once the available commercial antibiotic loaded polymethylmethacrylate bone cements (BC) are inadequate for local antibiotic treatment, especially against MRSA, the most commonly isolated and antibiotic-resistant pathogen in bone infections. In this paper a novel modified BC matrix loaded with minocycline is proposed. A renewed interest in this tetracycline arises due to its broad-spectrum of activity against the main organisms responsible for prosthetic joint infections, especially against MRSA. The modified BC matrices were evaluated concerning minocycline release profile, biomechanical properties, solid-state characterization, antimicrobial stability and biocompatibility under in vitro conditions. BC matrix loaded with 2.5% (w/wBC) of minocycline and 10.0% (w/wBC) of lactose presented the best properties since it completely released the loaded minocycline, maintained the mechanical properties and the antimicrobial activity against representative strains of orthopedic infections. In vitro biocompatibility was assessed for the elected matrix and neither minocycline nor lactose loading enhanced BC cytotoxicity.

The influence of vacuum mixing on methylmethacrylate liberation from acrylic cement powder

Polymethylmethacrylate (PMMA) bone cement is a biomaterial used to anchor prostheses during joint replacement surgery. Residual methylmethacrylate monomer (MMA) may be related with the cytotoxic effect of PMMA. The aim of the present paper was to investigate the effect of two different cement mixing methods: hand stirring at atmospheric pressure and under partial vacuum (0.330 and 0.154 bar) on residual monomer liberation in phosphate buffer saline solution from acrylic cement powder. Residual MMA content was determined by high-performance liquid chromatography. Mathematical models were applied to experimental dissolution data revealing that monomer release was significantly reduced in bone cement powder obtained at 0.154 bar vacuum pressure compared to the other mixing conditions. The kinetic models applied are consistent with a simple diffusion mechanism of the monomer from the polymer matrix.

Novel doped calcium phosphate-PMMA bone cement composites as levofloxacin delivery systems.

Antibiotic-loaded acrylic bone cements (ALABCs) are well-established and cost-effective materials to control the occurrence of bone and joint infections. However, the inexistence of alternative antibiotics other than those already commercially available and the poor ability to bind to bone tissue hampering its biological function are still major drawbacks of ALABCs clinical application. The concept of this research work is to develop a novel bone cement (BC) drug delivery system composed by Mg- and Sr-doped calcium phosphate (CaP) particles as drug carriers loaded into a lactose-modified acrylic BC, which, to the best of our knowledge, has never been reported. CaP particles are known to promote bone ingrowth and current research is focused on using these carriers as antibiotic delivery systems for the treatment of bone infections, like osteomyelitis. Levofloxacin is a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues and increasingly being recommended to manage bone-related infections. Also, the lactose-modified BC matrix, with a more porous structure, has already proved to enhance antibiotic release from the BC inner matrix. This novel BC composite biomaterial has shown improved mechanical integrity, biocompatibility maintenance, and sustained release of levofloxacin, with concentrations over the minimum inhibitory concentration values after a 48h while maintaining antibacterial activity over an 8-week period against Staphyloccocus aureus and Staphyloccocus epidermidis, common pathogens associated with bone infections.

Osteomyelitis: an overview of antimicrobial therapy

A osteomielite e um processo inflamatorio do tecido osseo, de origem infecciosa, que resulta em destruicao inflamatoria, necrose e formacao de novo osso. Pode aparecer em qualquer idade, afetar qualquer osso e tornar-se uma doenca cronica com morbidade persistente. Apesar dos progressos na quimioterapia infecciosa, o tratamento da osteomielite e caro e dificil, em particular quando associada a presenca de biofilmes bacterianos, especialmente de Staphylococcus aureus e Staphylococcus epidermidis. O tratamento da osteomielite inclui a administracao de doses elevadas de antibioticos (AB) por via endovenosa e oral, durante um periodo de pelo menos 6 semanas. Os sistemas de veiculacao localizada de farmacos, utilizando materiais nao biodegradaveis (polimetilmetacrilato) ou biodegradaveis e osteoativos como os cimentos osseos de ortofosfatos de calcio e vidro bioativo, surgiram como uma alternativa promissora para o tratamento da osteomielite. Estes sistemas permitem a veiculacao de AB in situ com concentracoes bactericidas por longos periodos de tempo e sem a toxicidade associada as outras vias de administracao. O presente trabalho propoe uma revisao da literatura relativa as causas, a patogenia e ao tratamento farmacologico da osteomielite. A metodologia do estudo da revisao consistiu numa pesquisa bibliografica, nas bases de dados Google Scholar, Science Direct, Pubmed, Springer link, B-on. Foram revistos e analisados diversos artigos publicados desde o ano de 1979.

Improvement of the antibacterial activity of daptomycin-loaded polymeric microparticles by Eudragit RL 100: an assessment by isothermal microcalorimetry.

The aim of the present study was to develop novel daptomycin-loaded acrylic microparticles with improved release profiles and antibacterial activity against two clinically relevant methicillin-susceptible and methicillin-resistant Staphylococcus aureus strains (MSSA and MRSA, respectively). Daptomycin was encapsulated into poly(methyl methacrylate) (PMMA) and PMMA-Eudragit RL 100 (EUD) microparticles by a double emulsion-solvent evaporation method. For comparison purposes similar formulations were prepared with vancomycin. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties, in vitro release and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. The addition of EUD to the formulation caused a shift in the surface charge of the particles from negative zeta potential values (100% PMMA formulations) to strongly positive. It also improved daptomycin encapsulation efficiency and release, whereas vancomycin encapsulation and release were strongly hindered. Plain and antibiotic-loaded particles presented comparable biocompatibility profiles. The antibacterial activity of the particles was assessed by isothermal microcalorimetry against both MSSA and MRSA. Daptomycin-loaded PMMA-EUD particles presented the highest antibacterial activity against both strains. The addition of 30% EUD to the daptomycin-loaded PMMA particles caused a 40- and 20-fold decrease in the minimum inhibitory (MIC) and bactericidal concentration (MBC) values, respectively, when compared to the 100% PMMA formulations. On the other hand, vancomycin-loaded microparticles presented the highest antibacterial activity in PMMA particles. Unlike conventional methods, isothermal microcalorimetry proved to be a real-time, sensitive and accurate method for assessment of antibacterial activity of antibiotic-loaded polymeric microparticles. Finally, the addition of EUD to formulations proved to be a powerful strategy to improve daptomycin encapsulation efficiency and release, and consequently improving the microparticles activity against two relevant S. aureus strains.

Nanoparticulate platforms for targeting bone infections: meeting a major therapeutic challenge

Bone infections are devastating complications in orthopedics due to biofilm formation. Treatment requires high antibiotic doses, which may lead to systemic toxicity thus limiting the drug therapeutic effectiveness. In this context, nanoparticles are well-known controlled release drug carriers that are able to modulate release rate, versatile in terms of administration routes and may be used as local delivery systems. Regarding bone infections, although nanoparticles are a promising strategy for overcoming biofilm tolerance, there are clearly technical, safety, regulatory and clinical challenges that need to be overcome before such nanomedicines may be translated into clinical use. In this paper, we present a critical overview on the high expectations against the real potential of the nanotechnological approaches to bone infection treatment.