Current Issue : April-June Volume : 2024 Issue Number : 2 Articles : 5 Articles
Limitations of bone defect reconstruction include poor bone healing and osteointegration with acrylic cements, lack of strength with bone putty/paste, and poor osteointegration. Tissue engineering aims to bridge these gaps through the use of bioactive implants. However, there is often a risk of infection and biofilm formation associated with orthopedic implants, which may develop anti-microbial resistance. To promote bone repair while also locally delivering therapeutics, 3D-printed implants serve as a suitable alternative. Soft, nanoporous 3D-printed filaments made from a thermoplastic polyurethane and polyvinyl alcohol blend, LAY-FOMM and LAY-FELT, have shown promise for drug delivery and orthopedic applications. Here, we compare 3D printability and sustained antibiotic release kinetics from two types of commercial 3D-printed porous filaments suitable for bone tissue engineering applications. We found that both LAY-FOMM and LAY-FELT could be consistently printed into scaffolds for drug delivery. Further, the materials could sustainably release Tetracycline over 3 days, independent of material type and infill geometry. The drug-loaded materials did not show any cytotoxicity when cultured with primary human fibroblasts. We conclude that both LAY-FOMM and LAY-FELT 3D-printed scaffolds are suitable devices for local antibiotic delivery applications, and they may have potential applications to prophylactically reduce infections in orthopedic reconstruction surgery....
Glioblastoma is a highly invasive and fatal disease. Temozolomide, a blood–brain barrier (BBB)-penetrant therapeutic agent currently used for glioblastoma, does not exhibit sufficient therapeutic effect. Cisplatin (CDDP), a versatile anticancer drug, is not considered a therapeutic option for glioblastoma due to its low BBB permeability. We previously investigated the utility of microbubbles (MBs) in combination with ultrasound (US) in promoting BBB permeability and reported the efficacy of drug delivery to the brain using a minimally invasive approach. This study aimed to evaluate the feasibility of CDDP delivery to the brain using the combination of MBs and US for the treatment of glioblastoma. We used mice that were implanted with glioma-261 GFP-Luc cells expressing luciferase as the glioblastoma model. In this model, after tumor inoculation, the BBB opening was induced using MBs and US, and CDDP was simultaneously administered. We found that the CDDP concentrations were higher at the glioblastoma site where the US was applied, although CDDP normally cannot pass through the BBB. Furthermore, the survival was longer in mice treated with CDDP delivered via MBs and US than in those treated with CDDP alone or those that were left untreated. These results suggest that the combination of MBs and US is an effective antitumor drug delivery system based on BBB opening in glioblastoma therapy....
Developing drugs that are highly selective to host tissues but are the least toxic remains one of the most difficult challenges in cancer treatment. Recent studies have shown that tumor cells from a variety of sources can express vitamin D3 receptors and that the response to vitamin D3 and its analogs is prone to growth arrest and cell death. However, conventional vitamin D3 drug formulations lack dose control and cannot target specific cells or tissues. The aim of this study was to prepare vitamin D3 nanospray for inhalation delivery route. This study evaluated the physical properties of the formulation (particle size distribution and biological stability), the total number of sprays per bottle, the spray volume per spray, and the loading variance of the spray. The optimized vitamin D3 spray formula is easy to spray, has fewer drips, and has a fast drying time. It can be stored for 3 months at 37 ± 2 ◦C temperature, 75 ± 5% relative humidity, and away from light, and can maintain biological stability. This study showed that compared with traditional nasal sprays, the spray has a larger fan angle (82.1 degrees) and beam width (104.88 mm), more symmetrical spray on both sides of the spray column, a faster coverage of the administration site, and a wider range, which is suitable for inhalation delivery routes....
We aimed to investigate the success rate of planned fixed quarterly aflibercept injections after three loading doses (QDA3L) to achieve stability without recurrence in neovascular age-related macular degeneration (nAMD) at a tertiary eye centre. A retrospective study was conducted over five years (2017–2021) by including all consecutive cases of nAMD treated with three initial aflibercept injections four weeks apart, followed by planned injection appointments every 12 to 16 weeks starting from week 20. The primary endpoint was to determine the proportion of patients who maintained disease inactivity at week 52 and week 104. A total of 40 eyes of 40 patients were included. The overall mean age was 80.8, with a male preponderance. The overall success rate in our study population was 52.9% and 53.6% at week 52 and week 104, respectively. The fovea remained dry at 85.3% at week 52 and 82.1% at week 104, and 85.3% and 85.7% of subjects lost fewer than 15 ETDRS letters at week 52 and week 104, respectively. While this study does not suggest the superiority of this regimen, the success and failure rates obtained in our study can be used in the counselling process for this particular fixed treatment regimen for nAMD....
Multidrug resistance (MDR) is a key factor in chemotherapy failure and tumor recurrence. The inhibition of drug efflux and autophagy play important roles inMDRtherapy. Herein, a multifunctional delivery system (HA-MIL-125@DVMA) was prepared for synergistically reverse tumor MDR. Tumor-targeted hollow MIL-125-Ti nanoparticles were used to load the doxorubicin–vitamin E succinate (DV) prodrug and 3-methyladenine (3-MA) to enhance reverse MDR effects. The pH-sensitive DV can kill tumor cells and inhibit P-gp-mediated drug efflux, and 3-MA can inhibit autophagy. HA-MIL-125@DVMA had uniformly distributed particle size and high drug-load content. The nanoparticles could effectively release the drugs into tumor microenvironment due to the rapid hydrazone bond-breaking under low pH conditions, resulting in a high cumulative release rate. In in vitro cellular experiments, the accumulation of HA-MIL-125@DVMA and HA-MIL-125@DV in MCF-7/ADR cells was significantly higher than that in the control groups. Moreover, the nanoparticles significantly inhibited drug efflux in the cells, ensuring the accumulation of the drugs in cell cytoplasm and causing drug-resistant cells’ death. Importantly, HA-MIL-125@DVMA effectively inhibited tumor growth without changes in body weight in tumor-bearing mice. In summary, the combination of the acid-sensitive prodrug DV and autophagy inhibitor 3-MA in a HA-MIL-125 nanocarrier can enhance the antitumor effect and reverse tumor MDR....
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