Controlled Release Of Antibiotics Research Articles

Optimizing revision arthroplasty: the role of customized articulating spacers

Introduction The advancement of surgery is set against a backdrop of continuous development and surgical innovations have transformed the way clinical care is delivered. Revision surgery might be required to address complications of primary arthroplasty. The first stage of revision arthroplasty would involve removal of an implant and placement of an antibiotic-impregnated cement spacer to maintain the joint space and stability, prevent soft tissue retraction, provide local antibiotic release and preserve bone tissue for revision implantation at the final stage of revision. Custom-made articulating spacers are a promising tool for optimizing the first stage of revision arthroplasty.The objective was to summarize the current data and present comprehensive information about spacers used in two-stage revision arthroplasty including manufacturing techniques, physical and chemical properties, clinical applications, the possibility of customization within the first stage of revision arthroplasty, current and promising directions for research.Material and methods The original literature search was conducted on key resources including Scientific Electronic Library (www.elibrary.ru), the National Library of Medicine (www.pubmed.org), the Cochraine Library (www.cochranelibrary.com) between 2018 and 2023 using search words and phrases: total arthroplasty, complications, revision arthroplasty, articulating spacer, periprosthetic joint infection, additive manufacturing, 3D printing.Results A comparative analysis of factory supplied, home-made, dynamic and static spacer models showed that the choice of articulating spacers for revision arthroplasty of major joints is of great relevance. Advantages of factory-made spacers include standardized range of sizes, the reliability and availability for medical institutions. They are characterized by limited use in repair of severe bone defects.Discussion Custom-made articulating spacers enable specific tailoring to accommodate individual defects. Despite high expectations from custom-made spacers, development of optimal technologies for rapid prototyping is essential. Investments in research and development in this area have the potential to create innovative solutions that can significantly improve the results of revision arthroplasty.Conclusion The paper explores the importance of systemization of knowledge about spacers and the role of new research in improving the design and functionality. Progress in the field of materials science, additive technologies and a personalized approach to spacer manufacturing can expand possibilities of revision arthroplasty and the effectiveness. Personalized approaches and improved methods of local drug delivery that provide controlled release of antibiotics can improve the results of treatment of periprosthetic joint infections.

Thermosensitive multivesicular liposomal hydrogel: a potential platform for loco-regional drug delivery in the treatment of osteomyelitis caused by antibiotic-resistant biofilm-forming bacteria.

Biofilm-mediated osteomyelitis presents significant therapeutic challenges. Given the limitations of existing osteomyelitis treatment approaches, there is a distinct need to develop a localized drug delivery system that is biocompatible, biodegradable, and capable of controlled antibiotic release. Multivesicular liposomes (MVLs), characterized by their non-concentric vesicular structure, distinct composition, and enhanced stability, serve as the system for a robust sustained-release drug delivery platform. In this study, various hydrogel formulations composed of poloxamer 407 and other hydrogels, incorporating vancomycin hydrochloride (VAN HL)-loaded MVLs (VAN HL-MVLs), were prepared and evaluated. The optimized VAN HL-MVL sol-gel system, consisting of poloxamer 407 and hyaluronic acid, successfully maintained drug release for up to 3 weeks and exhibited shear-thinning behavior at 37°C. While complete drug release from MVLs alone took place in 312 h, the hydrogel formulation extended this release to 504 h. The released drug effectively inhibited the Staphylococcus aureus biofilms growth within 24 h and methicillin-resistant S. aureus biofilms within 72 h. It also eradicated preformed biofilms of S. aureus and methicillin-resistant S. aureus in 96 and 120 h, respectively. This injectable in situ gel system incorporating VAN HL-MVLs holds potential as an alternative to undergoing multiple surgeries for osteomyelitis treatment and warrants further studies.

3D-printed porous titanium rods equipped with vancomycin-loaded hydrogels and polycaprolactone membranes for intelligent antibacterial drug release

Implant-related infections pose significant challenges to orthopedic surgeries due to the high risk of severe complications. The widespread use of bioactive prostheses in joint replacements, featuring roughened surfaces and tight integration with the bone marrow cavity, has facilitated bacterial proliferation and complicated treatment. Developing antibacterial coatings for orthopedic implants has been a key research focus in recent years to address this critical issue. Researchers have designed coatings using various materials and antibacterial strategies. In this study, we fabricated 3D-printed porous titanium rods, incorporated vancomycin-loaded mPEG750-b-PCL2500 gel, and coated them with a PCL layer. We then evaluated the antibacterial efficacy through both in vitro and in vivo experiments. Our coating passively inhibits bacterial biofilm formation and actively controls antibiotic release in response to bacterial growth, providing a practical solution for proactive and sustained infection control. This study utilized 3D printing technology to produce porous titanium rod implants simulating bioactive joint prostheses. The porous structure of the titanium rods was used to load a thermoresponsive gel, mPEG750-b-PCL2500 (PEG: polyethylene glycol; PCL: polycaprolactone), serving as a novel drug delivery system carrying vancomycin for controlled antibiotic release. The assembly was then covered with a PCL membrane that inhibits bacterial biofilm formation early in infection and degrades when exposed to lipase solutions, mimicking enzymatic activity during bacterial infections. This setup provides infection-responsive protection and promotes drug release. We investigated the coating’s controlled release, antibacterial capability, and biocompatibility through in vitro experiments. We established a Staphylococcus aureus infection model in rabbits, implanting titanium rods in the femoral medullary cavity. We evaluated the efficacy and safety of the composite coating in preventing implant-related infections using imaging, hematology, and pathology. In vitro experiments demonstrated that the PCL membrane stably protects encapsulated vancomycin during PBS immersion. The PCL membrane rapidly degraded at a lipase concentration of 0.2 mg/mL. The mPEG750-b-PCL2500 gel ensured stable and sustained vancomycin release, inhibiting bacterial growth. We investigated the antibacterial effect of the 3D-printed titanium material, coated with PCL and loaded with mPEG750-b-PCL2500 hydrogel, using a rabbit Staphylococcus aureus infection model. Imaging, hematology, and histopathology confirmed that our composite antibacterial coating exhibited excellent antibacterial effects and infection prevention, with good safety in trials. Our results indicate that the composite antibacterial coating effectively protects vancomycin in the hydrogel from premature release in the absence of bacterial infection. The outer PCL membrane inhibits bacterial growth and prevents biofilm formation. Upon contact with bacterial lipase, the PCL membrane rapidly degrades, releasing vancomycin for antibacterial action. The mPEG750-b-PCL2500 gel provides stable and sustained vancomycin release, prolonging its antibacterial effects. Our composite antibacterial coating demonstrates promising potential for clinical application.

Novel theranostic wounds dressing based on pH responsive alginate hydrogel/graphene oxide/levofloxacin modified silk

Integrating pH sensor with controlled antibiotic release is fabricated on silk to create a theranostic wound dressing. Alginate (ALG) hydrogel and graphene oxide (GO) loaded with levofloxacin (LVX) and a pH indicator are applied to fabricate a pH-responsive theranostic wound dressing. The modified silk color changes from yellow to green in response to elevated skin pH, indicating the skin infection. The semi-quantitative analysis was conducted using ImageJ, revealing significant color changes across the wide range. At elevated pH levels, the ionization of the COOH bonds within ALG induces repulsion among the COO− groups, thereby accelerating the release of the incorporated drug compared to release under lower pH. At an infected pH of 8, ALG hydrogel triggers LVX releasing up to 135.86 ± 0.3 µg, while at a normal pH of 7, theranostic silk releases 123.13 ± 0.26 µg. Incorporating GO onto silk fibers enhances LVX loading and sustains LVX release. Furthermore, these modified silks possess antimicrobial abilities without causing irritation or allergies on the human skin. This theranostic silks represents a major step forward in smart wound care, introducing a versatile platform of smart wound care.

Amikacin-Loaded Chitosan Hydrogel Film Cross-Linked with Folic Acid for Wound Healing Application.

Numerous carbohydrate polymers are frequently used in wound-dressing films because they are highly effective materials for promoting successful wound healing. In this study, we prepared amikacin (AM)-containing hydrogel films through the cross-linking of chitosan (CS) with folic acid along with methacrylic acid (MA), ammonium peroxodisulfate (APS), and methylenebisacrylamide (MBA). In the current studies, an effort has been made to look at the possibilities of these materials in developing new hydrogel film wound dressings meant for a slow release of the antibiotic AM and to enhance the potential for wound healing. Free-radical polymerization was used to generate the hydrogel film, and different concentrations of the CS polymer were used. Measurements were taken of the film thickness, weight fluctuation, folding resistance, moisture content, and moisture uptake. HPLC, FTIR, SEM, DSC, and AFM analyses were some of the different techniques used to confirm that the films were successfully developed. The AM release profile demonstrated regulated release over a period of 24 h in simulated wound media at pH 5.5 and 7.4, with a low initial burst release. The antibacterial activity against gram-negative bacterial strains exhibited substantial effectiveness, with inhibitory zones measuring approximately 20.5 ± 0.1 mm. Additionally, in vitro cytocompatibility assessments demonstrated remarkable cell viability, surpassing 80%, specifically when evaluated against human skin fibroblast (HFF-1) cells. The exciting findings of this study indicate the promising potential for further development and testing of these hydrogel films, offering effective and controlled antibiotic release to enhance the process of wound healing.

PH-Sensitive Drug Delivery System Based on Chitin Nanowhiskers-Sodium Alginate Polyelectrolyte Complex.

Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. Metronidazole (MET) delivery systems with the desired properties were obtained at pH 5.5 and an CNW:ALG ratio of 1:2. The MET–CNW–ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of −43 mV. In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. The introduction of CNWs into the MET–ALG system not only prolonged the drug release, but also increased the mucoadhesive properties by about 1.3 times. Thus, novel CNW–ALG hydrogels are promising carriers for pH sensitive drug delivery carriers.

Influence of Addition of Antibiotics on Chemical and Surface Properties of Sol-Gel Coatings.

Infection is one of the most common causes that leads to joint prosthesis failure. In the present work, biodegradable sol-gel coatings were investigated as a promising controlled release of antibiotics for the local prevention of infection in joint prostheses. Accordingly, a sol-gel formulation was designed to be tested as a carrier for 8 different individually loaded antimicrobials. Sols were prepared from a mixture of MAPTMS and TMOS silanes, tris(tri-methylsilyl)phosphite, and the corresponding antimicrobial. In order to study the cross-linking and surface of the coatings, a battery of examinations (Fourier-transform infrared spectroscopy, solid-state 29Si-NMR spectroscopy, thermogravimetric analysis, SEM, EDS, AFM, and water contact angle, thickness, and roughness measurements) were conducted on the formulations loaded with Cefoxitin and Linezolid. A formulation loaded with both antibiotics was also explored. Results showed that the coatings had a microscale roughness attributed to the accumulation of antibiotics and organophosphites in the surface protrusions and that the existence of chemical bonds between antibiotics and the siloxane network was not evidenced.

Exploring the Diverse Morphology of Porous Poly(Lactic Acid) Fibers for Developing Long-Term Controlled Antibiotic Delivery Systems.

In this study, we aimed to explore the morphologies of porous poly(lactic acid) (PLA) fibers through liquid–liquid phase separation, and investigate the relationship among pore formation, physical properties, and antibacterial activities of the fibers for identifying their potential as drug delivery carriers. Antibacterial activities of gentamicin-, kanamycin-, and amikacin-loaded PLA fibers against E. coli and S. epidermidis were evaluated. The antibacterial activity of drugs against E. coli showed the following profile: gentamicin > amikacin > kanamycin; however, S. epidermidis growth was almost completely inhibited immediately after the administration of all three drugs. The efficiency of gentamicin can be attributed to the electrostatic interactions between the positively and negatively charged antibiotic and bacterial cell membrane, respectively. Furthermore, gentamicin-loaded porous PLA fibers were evaluated as drug delivery systems. The cumulative amount of gentamicin in porous PLA nanofibers was considerably higher than that in other PLA fibers for 168 h, followed by 7:3 PLA > 6:4 PLA > 5:5 PLA > non-porous PLA. The 7:3 PLA fibers were projected to be ideal drug carrier candidates for controlled antibiotic release in delivery systems owing to their interconnected internal structure and the largest surface area (55.61 m2 g−1), pore size (42.19 nm), and pore volume (12.78 cm3 g−1).

Development of a novel smart carrier for drug delivery: Ciprofloxacin loaded vaterite/reduced graphene oxide/PCL composite coating on TiO2 nanotube coated titanium

In the field of orthopaedic implants, post-surgery infections and biocompatibility are the most challenging obstacles. Sustained and controlled antibiotic release is a key factor in novel drug delivery systems. A novel drug delivery system combined with vaterite microsphere, graphite oxide (GO), reduced graphene oxide (rGO) incorporated in a polycaprolactone (PCL) matrix on TiO2 nanotube coated Ti (TNT-Ti) is established. Anodization was employed to develop TiO2 nanotubular arrays on Ti. Ciprofloxacin hydrochloride (CPF–HCl) loaded vaterite microspheres were synthesized by in situ precipitation method. Deposition of vaterite/PCL, vaterite-GO/PCL and vaterite-rGO/PCL composite coating on TNT-Ti was carried out by dip coating method. The composite coatings were characterized for their phase content, morphological features and functional groups. Among the three types of composite coatings, vaterite-rGO/PCL composite coating is found to be capable of encapsulating CPF-HCl to a level of 75.14 μg. The drug release profile of CPF-HCl from the vaterite-rGO/PCL composite coating exhibits a controlled release amounting to only 35.02 % of release at the end of 120 h. The vaterite-rGO/PCL composite coating exhibits a low dissolution rate and possesses adequate bioactivity in HBSS and SBF solutions at 37 °C for 14 and 10 days, respectively. The in situ loaded CPF-HCL drug on vaterite microspheres, PCL polymer matrix and GO/rGO nanofillers does not affect the cytocompatibility and all the composite coatings supported cell viability and proliferation. The ability of vaterite-rGO/PCL composite coating to provide a slow and steady release of antibiotics with sufficient bioactivity and biocompatibility at the tissue implant interface makes it a promising for osteomyelitis infection of bone tissue implant materials.

PH-responsive self-healing of chemically modified tragacanth gum hydrogels as antibiotic release system

Herein, we reported pH-responsive self-healing hydrogels from cross-linked tragacanth gum (TG) as a controlled antibiotic release system using varying gum concentrations at changing temperatures using both glutaraldehyde and citric acid. TG-HGs can sustain multiple cycles of healing and separation by relatively maintaining their mechanical and healing properties. Cefazolin (Cf) loaded TG-HGs showed a respectively slow drug release over 8–24 h depend on the TG concentration. Prepared cf-loaded hydrogels showed excellent antibacterial activity against both gram-negative and gram-positive bacterium, and resulted in high mortality (99.3%) on S. aureus with a robust inhibition of biofilm formation.

DESIGN ALGINATE BASED BLENDS FOR LIVING COMPOSITE FIBERS TO PROMOTE WOUND HEALING

The currently used approaches in the treatment of wounds and burns have been studied for many years to eliminate problems related with mechanical strength, elasticity, biocompatibility and cost. Nowadays, fabrication of composite fibers by a fiber as core and hydrogels as shell, which can be seeded by cells is rapidly increasing. In this study, it is aimed to produce a natural polymer-based dressing that can provide controlled antibiotic release to accelerate wound healing with low cost and high efficiency. The composites have been achieved by using surgical suture as a core and alginate in the shell part, which modified with starch and gelatin. Evaluating low-cost hydrogel material such as alginate, starch and gelatin in the shell layer of composite fibers by different concentrations were investigated in addition to study their swelling and drug release behaviors. The parameters for the model of an antibiotic release that can prevent common infections can be manipulated by using a biotextile-based approach to quantify the amount of antibiotics and its release to satisfy clinical requirements. Toluidine blue and Penicillin/Streptomycin were chosen as antibiotic models for drug release experiments. Moreover, human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) were applied to evaluate cell viability experiments. Results demonstrated that alginate modified starch and gelatin can be used as low-cost and promising materials for use in biomedical applications.

Synergistic bactericidal nanofibers with photothermal controlled release of antibiotics triggered by near infrared

Herein, a type of nanofibrous membrane was prepared by co-electrospinning of polycaprolactone, poly(methyl methacrylate), polyaniline, and roxithromycin. The temperature of the nanofibers increased by 20 °C with 1 min of near infrared (NIR) radiation, and then the drug release was accelerated significantly. The bactericidal rate toward Staphylococcus aureus reached 99% with the synergistic effect of heat and antibiotics. This study provides a new approach to solving the problem of bacterial resistance by synergistic strategies involving photothermal and on-demand release of drugs.

Nanomaterial-based strategies in antimicrobial applications: Progress and perspectives

The dramatic increase of microbial resistances against conventional available antibiotics is a huge challenge to the effective treatment of infectious disease and thus becoming a daunting global threat of major concern, which necessitates the development of innovative therapeutics. Nanomaterial-based antimicrobial strategies have emerged as novel and promising tools to combat lethal bacteria and recalcitrant biofilm, featuring the abilities to evade existing drug resistance-related mechanisms. In this review, recent advances in “state-of-the-art” nanosystems which acting either as inherent therapeutics or nanocarriers for the precise delivery of antibiotics, are comprehensively summarized. Those nanosystems can effectively accumulate at the infectious sites, achieve multifunctional synergistic antibacterial efficacy, and provide controlled release of antibiotics in response to endogenous or exogenous stimulus (e.g., low pH, enzymes, or illumination). Especially, the nanoplatform that integrated with photothermal/photodynamic therapy (PTT/PDT) can enhance the bacterial destruction and biofilm penetration or ablation. In addition, nanoparticle-based approaches with enzymatically promoting bacterial killing, anti-virulence, and other mechanisms were also involved. Overall, this review provides crucial insights into the recent progress and remaining limitations of various antimicrobial nanotherapeutic strategies, and enlightens the further developments in this field simultaneously, which eventually benefiting public health.

672 An Investigation of Antibiotic Loading and Release in Acid-precipitated Keratin Proteins to Treat Topical Burn Infections

Abstract Introduction Human-hair derived keratin (KOS) protein has been selected in this investigation for its ability to bind antibiotic compounds and provide sustained release while withstanding harsh proteolytic environments such as inflamed, damaged tissue. The need to control local flora has been recognized as an imperative for wound healing, as recovery is significantly hampered by infection. This study investigates the synthesis of KOS-based particulate matter, developed using acid-precipitation, to load and release the water-soluble antibiotic ciprofloxacin (CIP). We hypothesize that ionically bound CIP release is tied to the degradation of KOS, therefore, bacterial metabolism, which produces proteolytic enzymes, will trigger CIP release thereby creating a novel self-extinguishing delivery system for contaminated skin wounds. Methods Ciprofloxacin hydrochloride was solubilized in deionized water (pH 5.3) under constant stirring. Freeze-dried KOS powder was added for an ultimately 5% w/v and 0.8% w/v solution of KOS and CIP, respectively. To improve the stability of KOS a water-soluble diglycidyl ether crosslinker was added to solutions and stirred for 24 hours. CIP-loaded protein was precipitated out by a hydrochloric acid induced pH reduction. Samples were collected and frozen at -20 °C prior to lyophilization, thus forming the stable product. Degradation of KOS and commensurate release of CIP were measured using a bicinchoninic acid (BCA) assay and fluorescent measurements of hydrated material supernatant. The reduction of bacterial colonies was validated by a broth inhibition assay whereby CIP-loaded KOS or unloaded KOS controls where hydrated in bacterial-laden broth cultures of Pseudomonas aeruginosa or Methicillin-resistant Staphylococcus aureus. Cultures were sampled at 24, 48, or 72 hours and plated to quantify colony-forming units. Results The presence of CIP in the KOS protein was confirmed and release rates follow similar patterns to that of KOS degradation. CIP-loaded proteins significantly reduce bacterial colony presence in concentrated inoculant solutions up to 72 hours. Conclusions CIP release does appear to coincide with KOS degradation, which is bolstered in the presence of infectious levels of bacteria. Ongoing studies aim to observe more robust models of infection and more controlled antibiotic release.

The antimicrobial activity and biocompatibility of a controlled gentamicin-releasing single-layer sol-gel coating on hydroxyapatite-coated titanium.

AimsThe aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses.MethodsCoatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods.ResultsThe coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface.ConclusionIn this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection.Cite this article: Bone Joint J 2021;103-B(3):522–529.

Abstract 6: Topical Antibiotic Elution In A Collagen-rich Hydrogel: Limiting Systemic Exposure To Antibiotics For Healing Of Infected Wounds

Purpose: Chronic wounds have become a prominent concern in the face of rising rates of obesity, peripheral vascular disease, and diabetes. Biofilms have been implicated in delayed wound closure. A novel collagen-rich hydrogel derived from human extracellular matrix presents an avenue for treating chronic wounds by providing appropriate extracellular proteins for healing and promoting neovascularization. Using the hydrogel as a delivery system for localized secretion of therapeutic dosage of antibiotics presents an attractive means of maximizing delivery while minimizing systemic side-effects. Methods: The authors investigated the elution of antibiotics from the collagen-rich hydrogel, and the efficacy of the treatment in disrupting biofilm in multiple models using Pseudomonas Aerginosa. Growth inhibition, biofilm disruption, and mammalian cell cytotoxicity were quantified. Results: The antibiotic-loaded hydrogel showed sustained release of antibiotics for up to 24 hours at therapeutic levels. The treatment inhibited bacteria growth and disrupted biofilm at multiple time points. The hydrogel was capable of accommodating various classes of antibiotics and did not result in cytotoxicity in mammalian fibroblasts or adipose stem cells Conclusions: An antibiotic-loaded collagen-rich hydrogel is capable of controlled antibiotic release without local cell death. A human-derived hydrogel possessing essential proteins for wound repair that is capable of eluting therapeutic levels of antibiotic is an exciting prospect in the field of chronic wound healing.

Biodegradable Antibacterial Polymeric Nanosystems: A New Hope to Cope with Multidrug-Resistant Bacteria.

The human society is faced with daunting threats from bacterial infections. Over decades, a variety of antibacterial polymeric nanosystems have exhibited great promise for the eradication of multidrug-resistant bacteria and persistent biofilms by enhancing bacterial recognition and binding capabilities. In this Review, the "state-of-the-art" biodegradable antibacterial polymeric nanosystems, which could respond to bacteria environments (e.g., acidity or bacterial enzymes) for controlled antibiotic release or multimodal antibacterial treatment, are summarized. The current antibacterial polymeric nanosystems can be categorized into antibiotic-containing and intrinsic antibacterial nanosystems. The antibiotic-containing polymeric nanosystems include antibiotic-encapsulated nanocarriers (e.g., polymeric micelles, vesicles, nanogels) and antibiotic-conjugated polymer nanosystems for the delivery of antibiotic drugs. On the other hand, the intrinsic antibacterial polymer nanosystems containing bactericidal moieties such as quaternary ammonium groups, phosphonium groups, polycations, antimicrobial peptides (AMPs), and their synthetic mimics, are also described. The biodegradability of the nanosystems can be rendered by the incorporation of labile chemical linkages, such as carbonate, ester, amide, and phosphoester bonds. The design and synthesis of the degradable polymeric building blocks and their fabrications into nanosystems are also explicated, together with their plausible action mechanisms and potential biomedical applications. The perspectives of the current research in this field are also described.

Prolonged and continuous antibacterial and anti-biofilm activities of thin films embedded with gentamicin-loaded mesoporous silica nanoparticles

The application of mesoporous silica nanoparticles (MSNs) in drug delivery systems has become highly attractive since the early 2000s. In this study, thin-film coatings embedded with gentamicin-loaded mesoporous silica nanoparticles (MSN-G) were prepared to provide antibacterial and anti-biofilm activity over a prolonged period of time. The prolonged and continuous activity of MSN-G films against Staphylococcus aureus throughout the release period was studied via two methods, namely, (1) disc diffusion of released gentamicin and (2) by shifting the MSN-G thin film to a new agar plate at certain time intervals. The expansion of the inhibition zone from 4.6 ± 0.5 to 9.7 ± 0.5 mm as caused by the released fraction of gentamicin from the first week to the eighth week indicated the controlled and slow release behaviour of loaded antibiotic and prolonged antibacterial efficacy of these films. In addition, the appearance of an inhibition zone after each shifting of the film to a new agar plate was persistent up to 103 days which confirmed that thin films successively prevented bacterial growth over a long period of time. In addition, the anti-biofilm activity of MSN-G films was evaluated by imaging bacterial cells attachment via confocal laser scanning microscopy and scanning electron microscopy. Remarkably, the anti-biofilm performance remained active for more than 2 months. To the best of our knowledge, such a slow and controlled release of antibiotic from nanoparticle embedded thin films with uninterrupted, continuous, and prolonged antibacterial effect for more than 2 months has not been reported yet.

Bioactivity and mechanical properties of scaffolds based on calcium aluminate and bioactive glass

Abstract Scaffolds were developed from mixtures of calcium aluminate (CA) and a bioactive glass (BG) and the effect of glass content on the mechanical strength and bioactivity of scaffolds was studied. Three different mixtures were tested: 95CA-5BG, 92.5CA-7.5BG and 90AC-10BG wt.%. Also, for comparison purposes, pure CA was used. In order to obtain the calcium aluminate cements (CAC), mixtures were hydrated using a water/mixture ratio by weight (w/c) of 0.4 and, with the resulting pastes, scaffolds were made by the lost-spheres method using PMMA beads. These materials showed interconnected pores (215 μm average diameter). Obtained scaffolds were loaded with antibiotic (gentamicin sulfate) and its release kinetics was studied. The evaluation of the in-vitro bioactivity was carried out by immersing scaffolds in a simulated body fluid (SBF) for 1, 7, 14 or 21 days at 36.5 °C. Compressive strength was evaluated before and after each immersion period. In all cases the formation of a Ca,P-rich compound on the surface of the scaffolds was detected after immersion in SBF. The amount of the bioactive compound formed as well as compressive strength increased as the amount of bioglass was increased. A controlled antibiotic release in SBF, with diffusion-controlled kinetics, was observed. In addition, scaffolds were not hemolytic. According to the results obtained, these materials are promising candidates for biomedical applications as drug delivery systems.

Cyclodextrin-mesoporous silica particle composites for controlled antibiotic release. A proof of concept toward colon targeting

Cyclodextrins (CDs) and mesoporous silica particles (MSPs) have been combined as composite carriers for controlled antibiotic release. CDs were employed as “gatekeeper” agents and grafted onto MSPs to retain drug molecules inside the MSP carrier. A variety of CDs (unfunctionalized, positively charged and carboxymethylated) and three different coupling strategies (covalent binding, electrostatic adsorption and inclusion complexation) were systematically investigated for their ability to control the release of two antibiotic drugs, metronidazole and clofazimine. The drugs had significantly different physicochemical properties (metronidazole − small hydrophilic, clofazimine- large hydrophobic). We report for the first time on the encapsulation and characterization of metronidazole-loaded-MSP.Each CD coating strategy reduced the drug release rate in phosphate buffer compared to unmodified MSP (from 20% to 100% retained drug). Covalent binding and inclusion complex approaches were significantly more effective than electrostatically adsorbed CD. In particular, the novel inclusion complex based on host/guest interaction between benzyl-modified silica surface and α-CD proved to be very effective (60–100% retained drug amount).Using pharmaceutical manufacturing processes, our study shows that CD-MSP composites can retain both hydrophobic and hydrophilic antibiotic compounds with potential translation to triggered release formulation targeting bacterial infections in the colon and lower intestine.