Core/Shell Nanoparticles: Classes, Properties, Synthesis Mechanisms, Characterization, and Applications

PLGA-based nanoparticles: An overview of biomedical applications

Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats.

Biocompatibility, Pharmaceutical and Biomedical Applications L. Harivardhan Reddy,†,‡ Jose ́ L. Arias, Julien Nicolas,† and Patrick Couvreur*,† †Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, Universite ́ Paris-Sud XI, UMR CNRS 8612, Faculte ́ de Pharmacie, IFR 141, 5 rue Jean-Baptiste Cleḿent, F-92296 Chat̂enay-Malabry, France Departamento de Farmacia y Tecnología Farmaceútica, Facultad de Farmacia, Campus Universitario de Cartuja s/n, Universidad de Granada, 18071 Granada, Spain ‡Pharmaceutical Sciences Department, Sanofi, 13 Quai Jules Guesdes, F-94403 Vitry-sur-Seine, France

Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications.

Sleep-induced apnea and disordered breathing refers to intermittent, cyclical cessations or reductions of airflow, with or without obstructions of the upper airway (OSA). In the presence of an anat...

Pathophysiology of Sleep Apnea

It is essential to determine the biodistribution, clearance, and biocompatibility of magnetic nanoparticles (MNPs) for in vivo biomedical applications to ensure their safe clinical use. We have studied these aspects with our novel iron oxide MNP formulation, which can be used as a magnetic resonance imaging (MRI) agent and a drug carrier system. Changes in serum and tissue iron levels were analyzed over 3 weeks after intravenous administration of MNPs to rats. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) levels, and total iron-binding capacity (TIBC) were also measured with time to assess the effect of MNPs on liver function. Selected tissues were also analyzed for oxidative stress and studied histologically to determine biocompatibility of MNPs. Serum iron levels gradually increased for up to 1 week but levels slowly declined thereafter. Biodistribution of iron in various body tissues changed with time but greater fraction of the injected iron localized in the liver and spleen than in the brain, heart, kidney, and lung. Magnetization measurements of the liver and spleen samples showed a steady decrease over 3 weeks, suggesting particle degradation. Serum showed a transient increase in ALT, AST, AKP levels, and TIBC over a period of 6-24 h following MNP injection. The increase in oxidative stress was tissue dependent, reaching a peak at approximately 3 days and then slowly declining thereafter. Histological analyses of liver, spleen, and kidney samples collected at 1 and 7 days showed no apparent abnormal changes. In conclusion, our MNPs did not cause long-term changes in the liver enzyme levels or induce oxidative stress and thus can be safely used for drug delivery and imaging applications.

Biodistribution, clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats.

Nanosystems in Drug Targeting: Opportunities and Challenges

Excessive production of reactive oxygen species (ROS) after cerebral ischemia and reperfusion is implicated in brain damage through different cellular and molecular mechanisms, and it is further aggravated by impaired cellular antioxidant defense systems under ischemic conditions. Therapeutic strategies based on exogenous delivery of the native form of superoxide dismutase (SOD), a free radical scavenger, are limited because of its short half-life (approximately 6 min) in vivo and poor permeability across the blood-brain-barrier (BBB). We encapsulated SOD in biodegradable poly(D,L-lactide co-glycolide) nanoparticles (SOD-NPs) and tested their efficacy in a rat focal cerebral ischemia-reperfusion injury model. We hypothesized that localized brain delivery of SOD-NPs would sustain the protective effect of SOD by neutralizing the deleterious effects of ROS formed following ischemia-reperfusion. SOD-NPs were administered at the time of reperfusion via the intracarotid route to maximize their localization in the brain. Animals receiving SOD-NPs (10,000 U of SOD/kg) demonstrated a 65% reduction in infarct volume, whereas an equivalent dose of SOD in solution (SOD-Sol) increased it by 25% over saline control (P<0.001; data at 6 h following reperfusion). Control NPs alone or mixed with SOD-Sol were ineffective in reducing infract volume, with results similar to saline control, indicating the protective effect of the encapsulated enzyme. SOD-NPs maintained BBB integrity, thereby preventing edema, reduced the level of ROS formed following reperfusion, and protected neurons from undergoing apoptosis. Animals treated with SOD-NPs demonstrated greater survival than those with saline control (75% vs. 0% at 28 days) and later regained most vital neurological functions. SOD-NPs may be an effective treatment option in conjunction with a thrombolytic agent for stroke patients.

Nanoparticle-mediated delivery of superoxide dismutase to the brain: an effective strategy to reduce ischemia-reperfusion injury

In the present study we investigated the involvement of the hypothalamic paraventricular nucleus (PVN) in the modulation of sympathoexcitatory reflex activated by peripheral and central chemoreceptors We measured mean arterial blood pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) before and after blocking neurotransmission within the PVN by bilateral microinjection of 2% lidocaine (100 nl) during specific stimulation of peripheral chemoreceptors by potassium cyanide (KCN, 75 microg/kg iv, bolus dose) or stimulation of central chemoreceptors with hypercapnia (10% CO(2)) Typically stimulation of peripheral chemoreceptors evoked a reflex response characterized by an increase in MAP, RSNA, and PNA and a decrease in HR Bilateral microinjection of 2% lidocaine into the PVN had no effect on basal sympathetic and cardiorespiratory variables; however, the RSNA and PNA responses evoked by peripheral chemoreceptor stimulation were attenuated (P < 005) Bilateral microinjection of bicuculline (50 pmol/50 nl, n = 5) into the PVN augmented the RSNA and PNA response to peripheral chemoreceptor stimulation (P < 005) Conversely, the GABA agonist muscimol (02 nmol/50 nl, n = 5) injected into the PVN attenuated these reflex responses (P < 005) Blocking neurotransmission within the PVN had no effect on the hypercapnia-induced central chemoreflex responses in carotid body denervated animals These results suggest a selective role of the PVN in processing the sympathoexcitatory and ventilatory component of the peripheral, but not central, chemoreflex

Differential role of the paraventricular nucleus of the hypothalamus in modulating the sympathoexcitatory component of peripheral and central chemoreflexes

Macro-, micro-, and nanogels are composed of soft materials (polymeric gels) that are of significant interest for applications in various areas of research including polymer and material science, physical and pharmaceutical sciences, medical sciences, and biotechnology. Hydrogels or macrogels are composed of hydrophilic polymeric chains that exhibit distinct property of good swelling capacity in aqueous media. Almost all water-soluble polymers containing hydrophilic functional groups such as –OH, –COOH, –NH2, –CONH2, –CONH, –SO2H, and so on, in their macromolecular chains are capable of producing hydrogels. The excellent properties of hydrogels such as high swelling capacity, hydrophilicity, and biocompatibility have enhanced their widespread applications in different fields including in agriculture and horticulture, health, bioengineering, pharmaceutical, food industry, and so on [1–13]. Microgels and nanogels are a special class of polymeric gel family that varies in size range from micrometer to submicrometer scale and exists as a three-dimensional network of hydrophilic and/or hydrophobic polymers. Microgels were first synthesized by Staudinger and Husemann in 1935 [14] and are defined as a disperse phase of

Maram K. Reddy

Papers

Biodistribution, clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats.

Nanosystems in Drug Targeting: Opportunities and Challenges

Nanoparticle-mediated delivery of superoxide dismutase to the brain: an effective strategy to reduce ischemia-reperfusion injury

Differential role of the paraventricular nucleus of the hypothalamus in modulating the sympathoexcitatory component of peripheral and central chemoreflexes

Nanogels: Chemistry to Drug Delivery