22 research outputs found
Injectable gellan gum-based nanoparticles-loaded system for the local delivery of vancomycin in osteomyelitis treatment
Infection spreading in the skeletal system
leading to osteomyelitis can be prevented by the prolonged
administration of antibiotics in high doses. However systemic
antibiotherapy, besides its inconvenience and often
low efficacy, provokes numerous side effects. Thus, we
formulated a new injectable nanoparticle-loaded system for
the local delivery of vancomycin (Vanc) applied in a
minimally-invasive way. Vanc was encapsulated in poly(Llactide-
co-glycolide) nanoparticles (NPs) by double-emulsification.
The size (258 ± 11 nm), polydispersity index
(0.240 ± 0.003) and surface potential (-25.9 ± 0.2 mV)
of NPs were determined by dynamic light scattering and
capillary electrophoresis measurements. They have a
spherical morphology and a smooth topography as
observed using atomic force microscopy. Vanc loading and
encapsulation efficiencies were 8.8 ± 0.1 and
55.2 ± 0.5 %, respectively, based on fluorescence spectroscopy
assays. In order to ensure injectability, NPs were
suspended in gellan gum and cross-linked with ; also a
portion of dissolved antibiotic was added to the system.
The resulting system was found to be injectable (extrusion
force 11.3 ± 1.1 N), reassembled its structure after
breaking as shown by rheology tests and ensured required
burst release followed by sustained Vanc delivery. The
system was cytocompatible with osteoblast-like MG-63
cells (no significant impact on cells’ viability was detected). Growth of Staphylococcus spp. reference strains
and also those isolated from osteomyelitic joints was
inhibited in contact with the injectable system. As a result
we obtained a biocompatible system displaying ease of
application (low extrusion force), self-healing ability after
disruption, adjustable drug release and antimicrobial
properties
Nanomedicine applications in orthopedic medicine: state of the art
Mozhdeh Mazaheri,1,* Niloofar Eslahi,1,* Farideh Ordikhani,1,* Elnaz Tamjid,2 Abdolreza Simchi1,3 1Department of Materials Science and Engineering, Sharif University of Technology, 2Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, 3Institute for Nanoscience and Nanotechnology, Sharif University of Technology, Tehran, Iran *These authors contributed equally to this work Abstract: The technological and clinical need for orthopedic replacement materials has led to significant advances in the field of nanomedicine, which embraces the breadth of nanotechnology from pharmacological agents and surface modification through to regulation and toxicology. A variety of nanostructures with unique chemical, physical, and biological properties have been engineered to improve the functionality and reliability of implantable medical devices. However, mimicking living bone tissue is still a challenge. The scope of this review is to highlight the most recent accomplishments and trends in designing nanomaterials and their applications in orthopedics with an outline on future directions and challenges. Keywords: orthopedics, nanomedicine, tissue engineering, implantable materials, nanotoxicolog
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Targeting antigen-presenting cells by anti-PD-1 nanoparticles augments antitumor immunity.
Recent studies in cancer research have focused intensely on the antineoplastic effects of immune checkpoint inhibitors. While the development of these inhibitors has progressed successfully, strategies to further improve their efficacy and reduce their toxicity are still needed. We hypothesized that the delivery of anti-PD-1 antibody encapsulated in PLGA nanoparticles (anti-PD-1 NPs) to the spleen would improve the antitumor effect of this agent. Unexpectedly, we found that mice treated with a high dose of anti-PD-1 NPs exhibited significantly higher mortality compared with those treated with free anti-PD-1 antibody, due to the overactivation of T cells. Administration of anti-PD-1 NPs to splenectomized LT-α-/- mice, which lack both lymph nodes and spleen, resulted in a complete reversal of this increased mortality and revealed the importance of secondary lymphoid tissues in mediating anti-PD-1-associated toxicity. Attenuation of the anti-PD-1 NPs dosage prevented toxicity and significantly improved its antitumor effect in the B16-F10 murine melanoma model. Furthermore, we found that anti-PD-1 NPs undergo internalization by DCs in the spleen, leading to their maturation and the subsequent activation of T cells. Our findings provide important clues that can lead to the development of strategies to enhance the efficacy of immune checkpoint inhibitors
Targeting antigen-presenting cells by anti–PD-1 nanoparticles augments antitumor immunity
Recent studies in cancer research have focused intensely on the antineoplastic effects of immune checkpoint inhibitors. While the development of these inhibitors has progressed successfully, strategies to further improve their efficacy and reduce their toxicity are still needed. We hypothesized that the delivery of anti-PD-1 antibody encapsulated in PLGA nanoparticles (anti-PD-1 NPs) to the spleen would improve the antitumor effect of this agent. Unexpectedly, we found that mice treated with a high dose of anti-PD-1 NPs exhibited significantly higher mortality compared with those treated with free anti-PD-1 antibody, due to the overactivation of T cells. Administration of anti-PD-1 NPs to splenectomized LT-α-/- mice, which lack both lymph nodes and spleen, resulted in a complete reversal of this increased mortality and revealed the importance of secondary lymphoid tissues in mediating anti-PD-1-associated toxicity. Attenuation of the anti-PD-1 NPs dosage prevented toxicity and significantly improved its antitumor effect in the B16-F10 murine melanoma model. Furthermore, we found that anti-PD-1 NPs undergo internalization by DCs in the spleen, leading to their maturation and the subsequent activation of T cells. Our findings provide important clues that can lead to the development of strategies to enhance the efficacy of immune checkpoint inhibitors