Helton José Wiggers

An adherent chitosan-based coating on polyethylene enables sustained moxifloxacin release and long-term antibacterial activity.

If untreated, skin wounds can lead to severe complications. Depending on the type of injury, long-term antibiotic administration is often required, and this decreases patient compliance. This limitation could be addressed by applying dressings capable of preventing infections by controlling drug release to the wound site. In this research, biodegradable wound dressings were investigated, based on natural polymers chitosan and alginate and incorporating the broad-spectrum gentamicin as antibiotic. Specifically, gentamicin was loaded into alginate nanoparticles, which were then loaded into chitosan-based films. This approach aimed at obtaining a system capable of modulating antibiotic release. The obtained nanoparticles had an average diameter of 86 nm and polydispersity index of 0.15. Antibiotic loading was around 600 µg/mg, with loading efficiency close to 100%. Films incorporating nanoparticles were compared to control films, which contained only gentamicin. Results showed that nanoparticles incorporation decreased film’s swelling in phosphate buffer saline, thus leading to a decrease in burst release while cytocompatibility for human dermal fibroblasts was maintained. Antibacterial activity was confirmed against both gram-positive and gram-negative bacteria. Moreover, the antibiotic was released as a function of pH, with distinct behavior at pHs ranging from 7.4 to 5.5. This indicates that alginate nanoparticles dispersed in chitosan films effectively release gentamicin on demand.

Sourcing and batch differences are often cited as intrinsic drawbacks for all natural polymers. Chitosan makes no exception. Chitosan is a biocompatible and biodegradable biopolymer with high potential for several biomedical applications, especially for releasing drugs and bactericidal and virucidal agents. Despite the potential of chitosan as a matrix for producing antibacterial films, the variability in its composition, stemming from its natural sources, can hinder the translation from bench to industry. To overcome this concern, we conducted a study to access the interchangeability of chitosan for the development of antibacterial drug release systems, in particular one system crosslinked with tannic acid and iron sulfate. Chitosans from different suppliers were characterized and used to synthetize films containing gentamicin, according to a previously reported protocol. The impact of molecular weight (M_W), deacetylation degree and purity on film properties and antibiotic release kinetics was assessed and results were compared. The films exhibited different initial bursts followed by similar sustained release profiles. All films exhibited antibacterial activity against both E. coli and S. aureus for at least 42 days. Moreover, films were cyto- and hemocompatible. Therefore, despite some differences in physicochemical properties, the interchangeability among the studied chitosan suppliers to produce antibacterial films is feasible, and the final product properties and performances are not significantly altered.

Background/Objectives: Medical devices are susceptible to bacterial colonization and biofilm formation, which can result in severe infections, leading to prolonged hospital stays and increased burden on society. Antibacterial films have the potential to assist in preventing biofilm formation, thereby reducing administration of antibiotics and the emergence of antibiotic-resistant strains. In a previous study, a chitosan-based matrix crosslinked with tannic acid and loaded with gentamicin was reported. In this study, five different antibiotics (moxifloxacin, ciprofloxacin, trimethoprim, sulfamethoxazole or linezolid) were loaded into these chitosan-based films, and their impact on the release behavior carefully assessed. Methods: The samples were characterized according to their thickness, swelling, and mass loss in phosphate-buffered saline (PBS), as well as by morphology using scanning electron microscopy (SEM) and optical phase contrast microscopy. Antibiotic release over time was quantified in PBS by high-performance liquid chromatography (HPLC). Antibacterial activity was investigated by disk diffusion test and antibiotic release over time. Finally, the cytotoxicity of the samples was assessed with human dermal fibroblasts. Results: The obtained results differed significantly, especially regarding the antibiotic release time and antibacterial activity, which varied from one day to six months, enabling classification of the films from burst/transient to prolonged release. The films also showed antibacterial features against bacteria mostly present in medical devices and displayed to be non-cytotoxic. Conclusions: In conclusion, it was demonstrated that the antibiotics structure significantly alters the release kinetics, and that by carefully selecting the antibiotic, the consequent release can be tuned. This approach yielded films that could be used for potentially-scalable release in antimicrobial coatings specific to medical devices, aiming to reduce biomaterial associated infections (BAIs).

Central venous catheters (CVCs) are largely used to administer chemotherapy, hemodialysis, and other treatments. Mostly made of polydimethylsiloxane (PDMS), these medical devices present an intrinsic risk of infection due to the possible formation of biofilm, thus increasing the risk of complications. Drug-releasing polymer coatings are a well-recognized strategy for combating biofilm formation. However, adhesion of the coating to the substrate over time is a major challenge. Therefore, this work aimed to design a chitosan-based coating designed to have maximum adhesion and stability to guarantee sustained drug release and antibacterial properties for at least 14 days. A coating composed of chitosan (CS) as a drug carrier, caffeic acid (CA) and copper sulphate (Cu) as crosslinkers, and moxifloxacin (Mox) as an antibiotic, was deposited through a controlled casting process onto functionalized PDMS surface. PDMS surface modification was investigated by X-ray photoelectron spectroscopy (XPS), and Fourier-transfer infrared (FTIR). Antibiotic release over time was measured in pseudo-physiological conditions (pH 7.4 and at 37 °C). Indirect cytotoxicity assays were performed on human dermal fibroblasts (HDF). The adhesion of the as-designed coating was evaluated by a specially designed pull-off test, before and after aging for 14 days in PBS. XPS and FTIR analyses confirmed the successful PDMS surface modification. The CS-CA-Cu-Mox coating resulted in being non-cytotoxic towards HDF and exhibited sustained moxifloxacin release for up to 49 days. Furthermore, the CS-CA and CS-CA-Cu coatings presented antibacterial activity for 21 days against E. coli, and for 14 days against S. aureus. Importantly, the coating maintained stable adhesion after 14 days in pseudo-physiological conditions. This study provides new insights into the adhesion behavior of polymeric coatings for medical devices, which is rarely reported in the literature.

A otite é uma inflamação no canal auditivo dos mamíferos, que se manifesta de forma aguda ou crônica. Os fatores que influenciam o surgimento desta doença são limpeza inadequada, imunossupressão e clima. Dependendo da região do ouvido afetada, a otite é classificada como externa, média ou interna. As espécies mais frequentemente acometidas pela doença são cães e gatos. A otite é causada por bactérias, fungos, vírus e alergias. A otite bacteriana é a mais comum e seu tratamento envolve o uso de antibióticos em diversas formas farmacêuticas, como soluções e suspensões. O uso contínuo e indiscriminado destes medicamentos pode causar resistência bacteriana, o que leva a uma busca constante de inovação em medicamentos. O presente trabalho é uma revisão bibliográfica de artigos publicados no período entre 2013 a 2024 com foco em novos medicamentos para otite, com destaque para a nanotecnologia em fase de estudos pré-clínicos. Durante esta década, avanços significativos foram alcançados. Exemplos de novas tecnologias incluem nanofibras, vesículas nanoelásticas e nanoemulsões, que oferecem melhor entrega e estabilidade dos medicamentos. As perspectivas são de que as novas gerações de medicamentos para otite utilizem a nanotecnologia.

Healthcare-associated infections (HAIs) represent a global burden, leading to significant mortality and generating financial costs. One important cause of HAIs is the microbiological contamination of implantable medical devices. In this context, a novel antimicrobial drug-eluting system, based on chitosan and loaded with gentamicin, a broad-spectrum antibiotic, was developed. The effects of the addition of tannic acid and different FeSO₄ concentrations on the loaded antibiotic release were evaluated. The properties of the films were assessed in terms of thickness, swelling, mass loss and wettability. The films’ surface composition was characterized by X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy. The antibiotic release in phosphate buffer saline was quantified by high-performance liquid chromatography–mass spectrometry, and the antibacterial activity was evaluated. Hemolysis and cytotoxicity were also assessed. The results showed that the addition of tannic acid and iron decreased the swelling degree and degradation due to strong interactions between the different components, thus impacting gentamicin release for up to 35 days. In conclusion, this study presents a novel strategy to produce low-cost and biocompatible antimicrobial drug-eluting systems with sustained and prolonged antibacterial activity over more than a month.

Natural polymer-based films, due to their favorable biological and mechanical properties, have demonstrated great potential as coatings for biomedical applications. Among them, chitosan films have been widely studied both as coating materials and as controlled drug release systems. Crosslinkers are often used to tune chitosan’s crosslinking degree and thus to control the drug release kinetics. For this purpose, quercetin, a plant-derived natural polyphenol, has gained attention as a crosslinker, mainly for its intrinsic anti-inflammatory, antioxidant, and antibacterial features. In this study, chitosan films crosslinked with three different concentrations of quercetin (10, 20, and 30% w/w) have been used as controlled release systems for the delivery of the antibacterial drug trimethoprim (TMP, 10% w/w). Physicochemical and antimicrobial properties were investigated. Surface wettability and composition of the films were assessed by contact angle measurements, X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR), respectively. The release kinetic of TMP in phosphate-buffered saline (PBS) and 2-(N-morpholino) ethanesulfonic acid (MES) was studied over time. Finally, antibacterial properties were assessed on E. coli and S. aureus through Kirby–Bauer disc diffusion and micro-dilution broth assays. Results show that quercetin, at the tested concentrations, clearly increases the crosslinking degree in a dose-dependent manner, thus influencing the release kinetic of the loaded TMP while maintaining its bactericidal effects. In conclusion, this work demonstrates that quercetin-crosslinked chitosan films represent a promising strategy for the design of antibiotic-releasing coatings for biomedical applications.