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Turkish Journal of Pharmaceutical... Jul 2023This study constructed dorzolamide (DRZ)-loaded ophthalmic implants for extended drug delivery and increased drug retention.
OBJECTIVES
This study constructed dorzolamide (DRZ)-loaded ophthalmic implants for extended drug delivery and increased drug retention.
MATERIALS AND METHODS
Carboxymethyl cellulose (CMC) and chitosan (CHI) were used to describe the ophthalmic implants. The implants were prepared by the solvent casting technique in presence of polyethylene glycol 6000 (PEG 6000) as plasticizer. Physicochemical characterization studies including mechanical characteristics [tensile strength (TS), elongation at break, and Young's modulus], bioadhesion studies, and and drug release studies were conducted.
RESULTS
TS of drug-loaded ophthalmic implants was 10.70 and 11.68 MPa, respectively. Elongation at break of CMC and CHI implants was 62.00% and 59.05%, respectively. The release profiles fit into Higuchi type kinetic model. release study results for both implants were correlated with release investigations.
CONCLUSION
CMC and CHI-based implants provide extended drug delivery. Implants prepared using CMC provided a significantly slower release rate, and drug retention on ocular surfaces increased. Thus, it has been concluded that DRZ-loaded CMC implants could provide effective treatment for glaucoma.
PubMed: 37417193
DOI: 10.4274/tjps.galenos.2022.95752 -
Annals of Medicine Dec 2023Infections are rare and poorly studied complications of unicompartmental knee arthroplasty (UKA) surgery. They are significantly less common compared to infections after...
BACKGROUND
Infections are rare and poorly studied complications of unicompartmental knee arthroplasty (UKA) surgery. They are significantly less common compared to infections after total knee arthroplasties (TKAs). Optimal management of periprosthetic joint infections (PJIs) after a UKA is not clearly defined in the literature. This article presents the results of the largest multicentre clinical study of UKA PJIs treated with Debridement, Antibiotics and Implant Retention (DAIR).
MATERIALS AND METHODS
In this retrospective case series, patients presenting between January 2016 and December 2019 with early UKA infection were identified at three specialist centres using the Musculoskeletal Infection Society (MSIS) criteria. All patients underwent a standardized treatment protocol consisting of the DAIR procedure and antibiotic therapy comprising two weeks of intravenous (IV) antibiotics followed by six weeks of oral therapy. The main outcome measure was overall survivorship free from reoperation for infection.
RESULTS
A total of 3225 UKAs (2793 (86.2%) medial and 432 (13.8%) lateral UKAs) were performed between January 2016 and December 2019. Nineteen patients had early infections necessitating DAIR. The mean follow-up period was 32.5 months. DAIR showed an overall survivorship free from septic reoperation of 84.2%, with overall survivorship free from all-cause reoperation of 78.95%.The most common bacteria were Coagulase-negative , and Group B . Three patients required a second DAIR procedure but remained free from re-infection at follow-up obviating the need for more demanding, staged revision surgery.
CONCLUSIONS
In infected UKAs, the DAIR procedure produces a high rate of success, with a high survivorship of the implant.Key messagesDebridement, Antibiotics and Implant Retention (DAIR) is a successful and minimally invasive surgical option for the management of periprosthetic joint infections (PJIs) after UKA.The surface area available for bacteria to colonise is much smaller in UKAs compared to total knee arthroplasties (TKAs), and this may account for the higher success rates of the DAIR procedure in infected UKAs versus infected TKAs.A second DAIR procedure can be considered in the management of the early recurrence of PJIs with a well-fixed UKA.
Topics: Humans; Arthroplasty, Replacement, Knee; Retrospective Studies; Debridement; Anti-Bacterial Agents; Treatment Outcome; Prosthesis-Related Infections; Arthritis, Infectious
PubMed: 37074322
DOI: 10.1080/07853890.2023.2179105 -
ACS Biomaterials Science & Engineering Aug 2023A recent U.S. Food and Drug Administration report presented the currently available scientific information related to biological response to metal implants. In this...
A recent U.S. Food and Drug Administration report presented the currently available scientific information related to biological response to metal implants. In this work, a multilevel approach was employed to assess the implant-induced and biocorrosion-related inflammation in the adjacent vascular tissue using a mouse stent implantation model. The implications of biocorrosion on peri-implant tissue were assessed at the macroscopic level via imaging and histomorphology. Elevated matrix metalloproteinase activity, colocalized with the site of implantation, and histological staining indicated that stent surface condition and implantation time affect the inflammatory response and subsequent formation and extent of neointima. Hematological measurements also demonstrated that accumulated metal particle contamination in blood samples from corroded-stetted mice causes a stronger immune response. At the cellular level, the stent-induced alterations in the nanostructure, cytoskeleton, and mechanical properties of circulating lymphocytes were investigated. It was found that cells from corroded-stented samples exhibited higher stiffness, in terms of Young's modulus values, compared to noncorroded and sham-stented samples. Nanomechanical modifications were also accompanied by cellular remodeling, through alterations in cell morphology and stress (F-actin) fiber characteristics. Our analysis indicates that surface wear and elevated metal particle contamination, prompted by corroded stents, may contribute to the inflammatory response and the multifactorial process of in-stent restenosis. The results also suggest that circulating lymphocytes could be a novel nanomechanical biomarker for peri-implant tissue inflammation and possibly the early stage of in-stent restenosis. Large-scale studies are warranted to further investigate these findings.
Topics: United States; Humans; Coronary Restenosis; Coronary Vessels; Stents; Metals; Inflammation
PubMed: 37480152
DOI: 10.1021/acsbiomaterials.3c00540 -
Autophagy and Biomaterials: A Brief Overview of the Impact of Autophagy in Biomaterial Applications.Pharmaceutics Sep 2023Macroautophagy (hereafter autophagy), a tightly regulated physiological process that obliterates dysfunctional and damaged organelles and proteins, has a crucial role... (Review)
Review
Macroautophagy (hereafter autophagy), a tightly regulated physiological process that obliterates dysfunctional and damaged organelles and proteins, has a crucial role when biomaterials are applied for various purposes, including diagnosis, treatment, tissue engineering, and targeted drug delivery. The unparalleled physiochemical properties of nanomaterials make them a key component of medical strategies in different areas, such as osteogenesis, angiogenesis, neurodegenerative disease treatment, and cancer therapy. The application of implants and their modulatory effects on autophagy have been known in recent years. However, more studies are necessary to clarify the interactions and all the involved mechanisms. The advantages and disadvantages of nanomaterial-mediated autophagy need serious attention in both the biological and bioengineering fields. In this mini-review, the role of autophagy after biomaterial exploitation and the possible related mechanisms are explored.
PubMed: 37765253
DOI: 10.3390/pharmaceutics15092284 -
ACS Nano Aug 2023Modest tissue penetrance, nonuniform distribution, and suboptimal release of drugs limit the potential of intracranial therapies against glioblastoma. Here, a...
Modest tissue penetrance, nonuniform distribution, and suboptimal release of drugs limit the potential of intracranial therapies against glioblastoma. Here, a conformable polymeric implant, μMESH, is realized by intercalating a micronetwork of 3 × 5 μm poly(lactic--glycolic acid) (PLGA) edges over arrays of 20 × 20 μm polyvinyl alcohol (PVA) pillars for the sustained delivery of potent chemotherapeutic molecules, docetaxel (DTXL) and paclitaxel (PTXL). Four different μMESH configurations were engineered by encapsulating DTXL or PTXL within the PLGA micronetwork and nanoformulated DTXL (nanoDTXL) or PTXL (nanoPTXL) within the PVA microlayer. All four μMESH configurations provided sustained drug release for at least 150 days. However, while a burst release of up to 80% of nanoPTXL/nanoDTXL was documented within the first 4 days, molecular DTXL and PTXL were released more slowly from μMESH. Upon incubation with U87-MG cell spheroids, DTXL-μMESH was associated with the lowest lethal drug dose, followed by nanoDTXL-μMESH, PTXL-μMESH, and nanoPTXL-μMESH. In orthotopic models of glioblastoma, μMESH was peritumorally deposited at 15 days post-cell inoculation and tumor proliferation was monitored via bioluminescence imaging. The overall animal survival increased from ∼30 days of the untreated controls to 75 days for nanoPTXL-μMESH and 90 days for PTXL-μMESH. For the DTXL groups, the overall survival could not be defined as 80% and 60% of the animals treated with DTXL-μMESH and nanoDTXL-μMESH were still alive at 90 days, respectively. These results suggest that the sustained delivery of potent drugs properly encapsulated in conformable polymeric implants could halt the proliferation of aggressive brain tumors.
Topics: Animals; Glioblastoma; Pharmaceutical Preparations; Nanoparticles; Paclitaxel; Docetaxel; Polymers; Polyvinyl Alcohol; Cell Line, Tumor
PubMed: 37379253
DOI: 10.1021/acsnano.3c01574 -
Nanomaterials (Basel, Switzerland) Nov 2023Zeolites and zeolitic imidazolate frameworks (ZIFs) are crystalline aluminosilicates with porous structure, which are closely linked with nanomaterials. They are... (Review)
Review
Zeolites and zeolitic imidazolate frameworks (ZIFs) are crystalline aluminosilicates with porous structure, which are closely linked with nanomaterials. They are characterized by enhanced ion exchange capacity, physical-chemical stability, thermal stability and biocompatibility, making them a promising material for dental applications. This review aimed to provide an overview of the application of zeolites and ZIFs in dentistry. The common zeolite compounds for dental application include silver zeolite, zinc zeolite, calcium zeolite and strontium zeolite. The common ZIFs for dental application include ZIF-8 and ZIF-67. Zeolites and ZIFs have been employed in various areas of dentistry, such as restorative dentistry, endodontics, prosthodontics, implantology, periodontics, orthodontics and oral surgery. In restorative dentistry, zeolites and ZIFs are used as antimicrobial additives in dental adhesives and restorative materials. In endodontics, zeolites are used in root-end fillings, root canal irritants, root canal sealers and bone matrix scaffolds for peri-apical diseases. In prosthodontics, zeolites can be incorporated into denture bases, tissue conditioners, soft denture liners and dental prostheses. In implantology, zeolites and ZIFs are applied in dental implants, bone graft materials, bone adhesive hydrogels, drug delivery systems and electrospinning. In periodontics, zeolites can be applied as antibacterial agents for deep periodontal pockets, while ZIFs can be embedded in guided tissue regeneration membranes and guided bone regeneration membranes. In orthodontics, zeolites can be applied in orthodontic appliances. Additionally, for oral surgery, zeolites can be used in oral cancer diagnostic marker membranes, maxillofacial prosthesis silicone elastomer and tooth extraction medicines, while ZIFs can be incorporated to osteogenic glue or used as a carrier for antitumour drugs. In summary, zeolites have a broad application in dentistry and are receiving more attention from clinicians and researchers.
PubMed: 37999327
DOI: 10.3390/nano13222973 -
Cancer Letters Apr 2024Pancreatic cancer poses a significant challenge within the field of oncology due to its aggressive behaviour, limited treatment choices, and unfavourable outlook. With a... (Review)
Review
Pancreatic cancer poses a significant challenge within the field of oncology due to its aggressive behaviour, limited treatment choices, and unfavourable outlook. With a mere 10% survival rate at the 5-year mark, finding effective interventions becomes even more pressing. The intricate relationship between desmoplasia and hypoxia in the tumor microenvironment further complicates matters by promoting resistance to chemotherapy and impeding treatment efficacy. The dense extracellular matrix and cancer-associated fibroblasts characteristic of desmoplasia create a physical and biochemical barrier that impedes drug penetration and fosters an immunosuppressive milieu. Concurrently, hypoxia nurtures aggressive tumor behaviour and resistance to conventional therapies. a comprehensive exploration of emerging medications and innovative drug delivery approaches. Notably, advancements in nanoparticle-based delivery systems, local drug delivery implants, and oxygen-carrying strategies are highlighted for their potential to enhance drug accessibility and therapeutic outcomes. The integration of these strategies with traditional chemotherapies and targeted agents reveals the potential for synergistic effects that amplify treatment responses. These emerging interventions can mitigate desmoplasia and hypoxia-induced barriers, leading to improved drug delivery, treatment efficacy, and patient outcomes in pancreatic cancer. This review article delves into the dynamic landscape of emerging anticancer medications and innovative drug delivery strategies poised to overcome the challenges imposed by desmoplasia and hypoxia in the treatment of pancreatic cancer.
Topics: Humans; Pharmaceutical Preparations; Drug Resistance, Neoplasm; Pancreatic Neoplasms; Antineoplastic Agents; Hypoxia; Tumor Microenvironment; Drug Delivery Systems
PubMed: 38453046
DOI: 10.1016/j.canlet.2024.216782 -
Annals of Biomedical Engineering Nov 2023Additive Manufacturing is noted for ease of product customization and short production run cost-effectiveness. As our global population approaches 8 billion, additive... (Review)
Review
Additive Manufacturing is noted for ease of product customization and short production run cost-effectiveness. As our global population approaches 8 billion, additive manufacturing has a future in maintaining and improving average human life expectancy for the same reasons that it has advantaged general manufacturing. In recent years, additive manufacturing has been applied to tissue engineering, regenerative medicine, and drug delivery. Additive Manufacturing combined with tissue engineering and biocompatibility studies offers future opportunities for various complex cardiovascular implants and surgeries. This paper is a comprehensive overview of current technological advancements in additive manufacturing with potential for cardiovascular application. The current limitations and prospects of the technology for cardiovascular applications are explored and evaluated.
Topics: Humans; Models, Cardiovascular; Bioengineering; Tissue Engineering; Prostheses and Implants; Biomedical Engineering
PubMed: 37466879
DOI: 10.1007/s10439-023-03322-x -
Bioactive Materials Mar 2024Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment. A...
Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment. A three-dimensional (3D)-printed porous Ti6Al4V scaffold (3DTi) is an ideal material for reconstructing critical bone defects with numerous advantages over traditional implants, including a lower elasticity modulus, stronger bone-implant interlock, and larger drug-loading space. Simvastatin is a multitarget drug with anti-tumor and osteogenic potential; however, its efficiency is unsatisfactory when delivered systematically. Here, simvastatin was loaded into a 3DTi using a thermosensitive poly (lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel as a carrier to exert anti-osteosarcoma and osteogenic effects. Newly constructed simvastatin/hydrogel-loaded 3DTi (Sim-3DTi) was comprehensively appraised, and its newfound anti-osteosarcoma mechanism was explained. Specifically, in a bone defect model of rabbit condyles, Sim-3DTi exhibited enhanced osteogenesis, bone in-growth, and osseointegration compared with 3DTi alone, with greater bone morphogenetic protein 2 expression. In our nude mice model, simvastatin loading reduced tumor volume by 59%-77 % without organic damage, implying good anti-osteosarcoma activity and biosafety. Furthermore, Sim-3DTi induced ferroptosis by upregulating transferrin and nicotinamide adenine dinucleotide phosphate oxidase 2 levels in osteosarcoma both and . Sim-3DTi is a promising osteogenic bone substitute for osteosarcoma-related bone defects, with a ferroptosis-mediated anti-osteosarcoma effect.
PubMed: 38045570
DOI: 10.1016/j.bioactmat.2023.11.001 -
Bioactive Materials Sep 2023Zinc (Zn) alloy porous scaffolds produced by additive manufacturing own customizable structures and biodegradable functions, having a great application potential for...
Zinc (Zn) alloy porous scaffolds produced by additive manufacturing own customizable structures and biodegradable functions, having a great application potential for repairing bone defect. In this work, a hydroxyapatite (HA)/polydopamine (PDA) composite coating was constructed on the surface of Zn-1Mg porous scaffolds fabricated by laser powder bed fusion, and was loaded with a bioactive factor BMP2 and an antibacterial drug vancomycin. The microstructure, degradation behavior, biocompatibility, antibacterial performance and osteogenic activities were systematically investigated. Compared with as-built Zn-1Mg scaffolds, the rapid increase of Zn, which resulted to the deteriorated cell viability and osteogenic differentiation, was inhibited due to the physical barrier of the composite coating. cellular and bacterial assay indicated that the loaded BMP2 and vancomycin considerably enhanced the cytocompatibility and antibacterial performance. Significantly improved osteogenic and antibacterial functions were also observed according to implantation in the lateral femoral condyle of rats. The design, influence and mechanism of the composite coating were discussed accordingly. It was concluded that the additively manufactured Zn-1Mg porous scaffolds together with the composite coating could modulate biodegradable performance and contribute to effective promotion of bone recovery and antibacterial function.
PubMed: 37180641
DOI: 10.1016/j.bioactmat.2023.04.017