Background: Innate immunity is of major importance in vascular repair. The present study evaluated whether systemic and transient depletion of monocytes and macrophages with liposome-encapsulated bisphosphonates inhibits experimental in-stent neointimal formation.
Methods And Results: Rabbits fed on a hypercholesterolemic diet underwent bilateral iliac artery balloon denudation and stent deployment. Liposomal alendronate (3 or 6 mg/kg) was given concurrently with stenting. Monocyte counts were reduced by >90% 24 to 48 hours after a single injection of liposomal alendronate, returning to basal levels at 6 days. This treatment significantly reduced intimal area at 28 days, from 3.88+/-0.93 to 2.08+/-0.58 and 2.16+/-0.62 mm2. Lumen area was increased from 2.87+/-0.44 to 3.57+/-0.65 and 3.45+/-0.58 mm2, and arterial stenosis was reduced from 58+/-11% to 37+/-8% and 38+/-7% in controls, rabbits treated with 3 mg/kg, and rabbits treated with 6 mg/kg, respectively (mean+/-SD, n=8 rabbits/group, P<0.01 for all 3 parameters). No drug-related adverse effects were observed. Reduction in neointimal formation was associated with reduced arterial macrophage infiltration and proliferation at 6 days and with an equal reduction in intimal macrophage and smooth muscle cell content at 28 days after injury. Conversely, drug regimens ineffective in reducing monocyte levels did not inhibit neointimal formation.
Conclusions: Systemic transient depletion of monocytes and macrophages, by a single liposomal bisphosphonates injection concurrent with injury, reduces in-stent neointimal formation and arterial stenosis in hypercholesterolemic rabbits.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1161/01.CIR.0000097002.69209.CD | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Alendronate Functionalized Bone-Targeting Pomolic Acid Liposomes Restore Bone Homeostasis for Osteoporosis Treatment.
Int J Nanomedicine
August 2024
Institute of Translational Medicine, Shanghai University, Shanghai, 200444, People's Republic of China.
Introduction: Osteoporosis, characterized by dysregulation of osteoclastic bone resorption and osteoblastic bone formation, severely threatens human health during aging. However, there is still no good therapy for osteoporosis, so this direction requires our continuous attention, and there is an urgent need for new drugs to solve this problem.
Methods: Traditional Chinese Medicine Salvia divinorum monomer pomolic acid (PA) could effectively inhibit osteoclastogenesis and ovariectomized osteoporosis.
Tumor Microenvironment Reprogramming Improves Nanomedicine-Based Chemo-Immunotherapy in Sarcomas.
Mol Cancer Ther
November 2024
Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus.
Article Synopsis
- Sarcomas are rare and complex cancers originating in soft tissues or bones, making their treatment difficult due to a challenging tumor microenvironment (TME) that limits drug delivery.
- A study tested the drug ketotifen in combination with advanced chemotherapy and immunotherapy techniques in mouse models, which showed that ketotifen improved the TME by reducing tumor stiffness and increasing blood flow, leading to better treatment outcomes.
- This treatment combination also enhanced immune response by increasing the presence of effective T-cells and altering macrophage activity, suggesting a promising approach for improving therapeutic efficacy in sarcoma patients.
Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent.
Beilstein J Nanotechnol
May 2024
Nanomedicine Research and Development Centre (NARD), Science and Technology Department, National University of Quilmes, Roque Sáenz Peña 352, Bernal, Buenos Aires, Argentina.
Sodium alendronate (ALN) is a very hydrosoluble and poorly permeable molecule used as an antiresorptive agent and with vascular anticalcifying capacity. Loaded into targeted nanovesicles, its anti-inflammatory activity may be amplified towards extra-osseous and noncalcified target cells, such as severely irritated vascular endothelium. Here cytotoxicity, mitochondrial membrane potential, ATP content, and membrane fluidity of human endothelial venous cells (HUVECs) were determined after endocytosis of ALN-loaded nanoarchaeosomes (nanoARC-Chol(ALN), made of polar lipids from : cholesterol 7:3 w/w, 166 ± 5 nm, 0.
View Article and Find Full Text PDFHarnessing Nanomedicine to Potentiate the Chemo-Immunotherapeutic Effects of Doxorubicin and Alendronate Co-Encapsulated in Pegylated Liposomes.
Pharmaceutics
November 2023
Department of Immunotherapeutics and Biotechnology, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX 79601, USA.
Encapsulation of Doxorubicin (Dox), a potent cytotoxic agent and immunogenic cell death inducer, in pegylated (Stealth) liposomes, is well known to have major pharmacologic advantages over treatment with free Dox. Reformulation of alendronate (Ald), a potent amino-bisphosphonate, by encapsulation in pegylated liposomes, results in significant immune modulatory effects through interaction with tumor-associated macrophages and activation of a subset of gamma-delta T lymphocytes. We present here recent findings of our research work with a formulation of Dox and Ald co-encapsulated in pegylated liposomes (PLAD) and discuss its pharmacological properties vis-à-vis free Dox and the current clinical formulation of pegylated liposomal Dox.
View Article and Find Full Text PDFPegylated Liposomal Alendronate Biodistribution, Immune Modulation, and Tumor Growth Inhibition in a Murine Melanoma Model.
Biomolecules
August 2023
Department of Immunotherapeutics and Biotechnology, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX 79601, USA.
While tumor-associated macrophages (TAM) have pro-tumoral activity, the ablation of macrophages in cancer may be undesirable since they also have anti-tumoral functions, including T cell priming and activation against tumor antigens. Alendronate is a potent amino-bisphosphonate that modulates the function of macrophages in vitro, with potential as an immunotherapy if its low systemic bioavailability can be addressed. We repurposed alendronate in a non-leaky and long-circulating liposomal carrier similar to that of the clinically approved pegylated liposomal doxorubicin to facilitate rapid clinical translation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!