Brain-targeted delivery of doxorubicin using glutathione-coated nanoparticles for brain cancers.
Antibiotics; Animals; *Drug Delivery Systems; Rats; Cell Line; Polylactic Acid-Polyglycolic Acid Copolymer; Blood-Brain Barrier/*metabolism; Brain cancer; Brain Neoplasms/drug therapy/metabolism; brain-targeted delivery; doxorubicin; Doxorubicin/*administration & dosage/pharmacokinetics; Drug Carriers/*chemistry/metabolism; Glutathione/*chemistry/metabolism; Lactic Acid/chemistry/metabolism; Nanoparticles/*chemistry/metabolism; PLGA-PEG NP; Polyethylene Glycols/chemistry/metabolism; Polyglycolic Acid/chemistry/metabolism; Tumor; Antineoplastic/*administration & dosage/pharmacokinetics
OBJECTIVES: To prepare and characterize in vitro a novel brain-targeted delivery of doxorubicin using glutathione-coated nanoparticles (NPs) for the treatment of brain cancer. METHODS: Doxorubicin-loaded NPs were prepared by the nanoprecipitation method using PLGA-COOH (dl-lactide-co-glycolide). The NPs were coated with a glutathione-PEG conjugate (PEG-GSH) in order to target delivery to the brain. The NPs were characterized via in vitro studies to determine particle size, drug release, cellular uptake, immunofluorescence study, cytotoxic assay, and in vitro blood-brain barrier (BBB) assay. RESULTS: The NPs showed a particle size suitable for BBB permeation (particle size around 200 nm). The in vitro release profile of the NPs exhibited no initial burst release and showed sustained drug release for up to 96 h. The immunofluorescence study showed the glutathione coating does not interfere with the drug release. Furthermore, in vitro BBB Transwell study showed significantly higher permeation of the doxorubicin-loaded NPs compared with the free doxorubicin solution through the coculture of rat brain endothelial (RBE4) and C6 astrocytoma cells (p \textless 0.05). CONCLUSIONS: We conclude that the initial in vitro characterization of the NPs demonstrates potential in delivering doxorubicin to cancer cells with possible future application in targeting brain cancers in vivo.
Geldenhuys Werner; Wehrung Daniel; Groshev Anastasia; Hirani Anjali; Sutariya Vijaykumar
Pharmaceutical development and technology
2015
2015-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.3109/10837450.2014.892130" target="_blank" rel="noreferrer noopener">10.3109/10837450.2014.892130</a>
Brain-targeted delivery of Tempol-loaded nanoparticles for neurological disorders.
Animals; Rats; Cell Line; Nanoparticles; Polylactic Acid-Polyglycolic Acid Copolymer; Particle Size; Delayed-Action Preparations; Antibodies; Polyethylene Glycols; Blood-Brain Barrier/metabolism; *Lactic Acid; *Polyglycolic Acid; Antioxidants/chemistry/*metabolism; Cross-Linking Reagents/chemistry; Cyclic N-Oxides/chemistry/*metabolism; Free Radical Scavengers/chemistry/*metabolism; Maleimides/chemistry; Spin Labels; Transferrin/*immunology; Tumor; Monoclonal/chemistry/*metabolism
Brain-targeted Tempol-loaded poly-(lactide-co-glycolide) (PLGA) nanoparticles (NPs) conjugated with a transferrin antibody (OX 26) were developed using the nanoprecipitation method. These NPs may have utility in treating neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Central to these diseases is an increased production of reactive oxygen and nitrogen species which may take part in the development of these conditions. As proof of principle, the NPs were loaded with Tempol, a free radical scavenger that has been shown to be protective against oxidative insults. To enhance the delivery of NPs to the central nervous system (CNS), we conjugated the transferrin receptor antibody covalently to PLGA NPs using the
Carroll Richard T; Bhatia Deepak; Geldenhuys Werner; Bhatia Ruchi; Miladore Nicholas; Bishayee Anupam; Sutariya Vijaykumar
Journal of drug targeting
2010
2010-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.3109/10611861003639796" target="_blank" rel="noreferrer noopener">10.3109/10611861003639796</a>
Design and assessment of a tissue-engineered model of human phalanges and a small joint.
*Bioartificial Organs; *Biomimetic Materials; *Finger Joint; *Finger Phalanges; *Tissue Engineering; Animals; Biological; Bone and Bones; Cartilage; Cattle; Humans; Lactic Acid; Mice; Models; Nude; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Tendons
OBJECTIVES: To develop models of human phalanges and small joints by suturing different cell-polymer constructs that are then implanted in athymic (nude) mice. DESIGN: Models consisted of bovine periosteum, cartilage, and/or tendon cells seeded onto biodegradable polymer scaffolds of either polyglycolic acid (PGA) or copolymers of PGA and poly-L-lactic acid (PLLA) or poly-epsilon-caprolactone (PCL) and PLLA. Constructs were fabricated to produce a distal phalanx, middle phalanx, or distal interphalangeal joint. SETTING AND SAMPLE POPULATION: Studies of more than 250 harvested implants were conducted at the Northeastern Ohio Universities College of Medicine. EXPERIMENTAL VARIABLE: Polymer scaffold, cell type, and implantation time were examined. OUTCOME MEASURE: Tissue-engineered specimens were characterized by histology, transmission electron microscopy, in situ hybridization, laser capture microdissection and qualitative and quantitative polymerase chain reaction analysis, magnetic resonance microscopy, and X-ray microtomography. RESULTS: Over periods to 60 weeks of implantation, constructs developed through vascularity from host mice; formed new cartilage, bone, and/or tendon; expressed characteristic genes of bovine origin, including type I, II and X collagen, osteopontin, aggrecan, biglycan, and bone sialoprotein; secreted corresponding proteins; responded to applied mechanical stimuli; and maintained shapes of human phalanges with small joints. CONCLUSION: Results give insight into construct processes of tissue regeneration and development and suggest more complete tissue-engineered cartilage, bone, and tendon models. These should have significant future scientific and clinical applications in medicine, including their use in plastic surgery, orthopaedics, craniofacial reconstruction, and teratology.
Landis W J; Jacquet R; Hillyer J; Lowder E; Yanke A; Siperko L; Asamura S; Kusuhara H; Enjo M; Chubinskaya S; Potter K; Isogai N
Orthodontics & craniofacial research
2005
2005-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/j.1601-6343.2005.00353.x" target="_blank" rel="noreferrer noopener">10.1111/j.1601-6343.2005.00353.x</a>
Alignment of inducible vascular progenitor cells on a micro-bundle scaffold improves cardiac repair following myocardial infarction.
*Cardiovascular regeneration; *Ischemic heart diseases; *Micro-bundle scaffold; *Myocardial infarction; *Neovascularization; *Stem cells; *Tissue Scaffolds; *Vascular progenitor cells; Animal; Animals; Cell Differentiation; Cell Proliferation; Cell Survival; Cells; Coculture Techniques; Cultured; Disease Models; Endothelial Progenitor Cells/metabolism/*transplantation; Fibroblast Growth Factor 2/metabolism; Lactic Acid/*chemistry; Muscle; Myocardial Infarction/metabolism/pathology/physiopathology/*surgery; Myocardium/metabolism/*pathology; Myocytes; Paracrine Communication; Phenotype; Physiologic; Polyglycolic Acid/*chemistry; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Signal Transduction; Smooth; Smooth Muscle/metabolism/*transplantation; Sprague-Dawley; Time Factors; Tissue Engineering/*methods; Vascular Endothelial Growth Factor A/metabolism; Vascular/metabolism/*transplantation; Ventricular Remodeling
Ischemic heart disease is still the leading cause of death even with the advancement of pharmaceutical therapies and surgical procedures. Early vascularization in the ischemic heart is critical for a better outcome. Although stem cell therapy has great potential for cardiovascular regeneration, the ideal cell type and delivery method of cells have not been resolved. We tested a new approach of stem cell therapy by delivery of induced vascular progenitor cells (iVPCs) grown on polymer micro-bundle scaffolds in a rat model of myocardial infarction. iVPCs partially reprogrammed from vascular endothelial cells (ECs) had potent angiogenic potential and were able to simultaneously differentiate into vascular smooth muscle cells (SMCs) and ECs in 2D culture. Under hypoxic conditions, iVPCs also secreted angiogenic cytokines such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) as measured by enzyme-linked immunosorbent assay (ELISA). A longitudinal micro-scaffold made from poly(lactic-co-glycolic acid) was sufficient for the growth and delivery of iVPCs. Co-cultured ECs and SMCs aligned well on the micro-bundle scaffold similarly as in the vessels. 3D cell/polymer micro-bundles formed by iVPCs and micro-scaffolds were transplanted into the ischemic myocardium in a rat model of myocardial infarction (MI) with ligation of the left anterior descending artery. Our in vivo data showed that iVPCs on the micro-bundle scaffold had higher survival, and better retention and engraftment in the myocardium than free iVPCs. iVPCs on the micro-bundles promoted better cardiomyocyte survival than free iVPCs. Moreover, iVPCs and iVPC/polymer micro-bundles treatment improved cardiac function (ejection fraction and fractional shortening, endocardial systolic volume) measured by echocardiography, increased vessel density, and decreased infarction size [endocardial and epicardial infarct (scar) length] better than untreated controls at 8 weeks after MI. We conclude that iVPCs grown on a polymer micro-bundle scaffold are new promising approach for cell-based therapy designed for cardiovascular regeneration in ischemic heart disease.
Jamaiyar Anurag; Wan Weiguo; Ohanyan Vahagn; Enrick Molly; Janota Danielle; Cumpston Devan; Song Hokyung; Stevanov Kelly; Kolz Christopher L; Hakobyan Tatev; Dong Feng; Newby Bi-Min Zhang; Chilian William M; Yin Liya
Basic research in cardiology
2017
2017-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00395-017-0631-4" target="_blank" rel="noreferrer noopener">10.1007/s00395-017-0631-4</a>