Dye Delivery Research Articles

Individual and simultaneous encapsulation and delivery of incompatible dyes in biocompatible multicompartment terpolymer micelles

Multicompartment micelles (MCMs) can deliver incompatible drug payloads because MCMs derive from the self-assembly of a terpolymer containing one hydrophilic block and two incompatible solvophobic blocks. In particular, MCMs resulting from the self-assembly of poly((sulfamate-carboxylate)isoprene)-block-polystyrene-block-poly(ethylene oxide) (PISC-b-PS-b-PEO) undergo irreversible transition to regular micelles at an alkaline pH. However, several aspects of these MCMs remain unexplored, such as the chemical transformation of PISC-b-PS-b-PEO into an amino-acid functional terpolymer, potential applications of these nanoparticles as dual drug delivery systems and their biocompatibility. In exploring these opportunities, we found that more than 90% of N-S bonds of sulfamate groups (of the PISC block) are cleaved upon acidic treatment of PISC-b-PS-b-PEO terpolymers, which are chemically transformed into a new polyzwitterion triblock terpolymer, that is, poly((amino-carboxylate)isoprene)-block-polystyrene-block-poly(ethylene oxide) (PACIS-b-PS-b-PEO), but retain their MCM morphology. Into these MCMs, two incompatible (Nile Red (hydrophobic) and eosin (hydrophilic)) guest molecules can be loaded separately and together in the predesigned cores without significantly disturbing the structure, as shown by cryo-TEM and light scattering. In addition to their high stability, PACIS-b-PS-b-PEO MCMs are also pH-responsive, whether loaded or unloaded, based on fluorescence spectroscopy and light scattering. In cytotoxicity tests, loaded and unloaded PACIS-b-PS-b-PEO nanoparticles proved nontoxic to various cell lines, including Balb/3T3 and MCF10A, with efficient cellular uptake, as shown by fluorescence imaging. Therefore, our findings highlight PACIS-b-PS-b-PEO as a versatile platform for preparing MCMs for multiple drug delivery.

Optical Estimation of Bioelectric Patterns in Living Embryos.

Fluorescent lifetime imaging (FLIM) is a powerful tool for visualizing physiological parameters in vivo. We present here a 3-dye strategy for mapping bioelectric patterns in living Xenopus laevis embryos leveraging the quantitative power of fluorescent lifetime imaging. We discuss a general strategy for disentangling physiological artifacts from true bioelectric signals, a method for dye delivery via transcardial injection, and how to visualize and interpret the fluorescent lifetime of the dyes in vivo.

Influence of focused ultrasound on locoregional drug delivery to the brain: Potential implications for brain tumor therapy

IntroductionEfficient delivery of therapeutics across the blood-brain barrier (BBB) for the treatment of central nervous system (CNS) tumors is a major challenge to the development of safe and efficacious therapies. Locoregional drug delivery platforms offer an improved therapeutic index by achieving high drug concentrations in the target tissue with negligible systemic exposure. Intrathecal (intraventricular) [IT] and convection-enhanced delivery [CED] are two clinically relevant methods being employed for various CNS malignancies. Both of these standalone platforms suffer from passive post-administration distribution forces, sometimes limiting the desired distribution for tumor therapy. Focused ultrasound and microbubble-mediated blood-brain barrier opening (FUS-BBBO) is a recent modality used for enhanced drug delivery. It is postulated that coupling of FUS with these alternative delivery routes may provide benefits. Multimodality FUS may provide the desired ability to increase the depth of parenchymal delivery following IT administration and provide a means for contour directionality with CED. Further, the transient enhanced permeability achieved with FUS-BBBO is well established, but drug residence and transit times, important to clinical dose scheduling, have not yet been defined. The present investigation comprises two discrete studies: 1. Conduct a comprehensive quantitative evaluation to elucidate the effect of FUS-BBBO as it relates to varying routes of administration (IT and IV) in its capacity to facilitate drug penetration within the striatal-thalamic region. 2. Investigate the impact of combining FUS-BBBO with CED on drug distribution, with a specific focus on the temporal dynamics of drug retention within the target region. MethodsFirstly, we quantitatively assessed how FUS-BBBO coupled with IT and IV altered fluorescent dye (Dextran 2000 kDa and 70 kDa) distribution and concentration in a predetermined striatal-thalamic region in naïve mice. Secondly, we analyzed the pharmacokinetic effects of using FUS mediated BBB disruption coupled with CED by measuring the volume of distribution and time-dependent concentration of the dye. ResultsOur results indicate that IV administration coupled with FUS-BBBO successfully enhances delivery of dye into the pre-defined sonication targets. Conversely, measurable dye in the sonication target was consistently less after IT administration. FUS enhances the distribution volume of dye after CED. Furthermore, a shorter time of residence was observed when CED was coupled with FUS-BBBO application when compared to CED alone. Conclusion1. Based on our findings, IV delivery coupled with FUS-BBBO is a more efficient means for delivery to deep targets (i.e. striatal-thalamic region) within a predefined spatial conformation compared to IT administration. 2. FUS-BBBO increases the volume of distribution (Vd) of dye after CED administration, but results in a shorter time of residence. Whether this finding is reproducible with other classes of agents (e.g., cytotoxic agents, antibodies, viral particles, cellular therapies) needs to be studied.

Using Vertically Aligned Carbon Nanofiber Arrays on Rigid or Flexible Substrates for Delivery of Biomolecules and Dyes to Plants.

The delivery of biomolecules and impermeable dyes to intact plants is a major challenge. Nanomaterials are up-and-coming tools for the delivery of DNA to plants. As exciting as these new tools are, they have yet to be widely applied. Nanomaterials fabricated on rigid substrate (backing) are particularly difficult to successfully apply to curved plant structures. This study describes the process for microfabricating vertically aligned carbon nanofiber arrays and transferring them from a rigid to a flexible substrate. We detail and demonstrate how these fibers (on either rigid or flexible substrates) can be used for transient transformation or dye (e.g., fluorescein) delivery to plants. We show how VACNFs can be transferred from rigid silicon substrate to a flexible SU-8 epoxy substrate to form flexible VACNF arrays. To overcome the hydrophobic nature of SU-8, fibers in the flexible film were coated with a thin silicon oxide layer (2-3 nm). To use these fibers for delivery to curved plant organs, we deposit a 1 µL droplet of dye or DNA solution on the fiber side of VACNF films, wait 10 min, place the films on the plant organ and employ a swab with a rolling motion to drive fibers into plant cells. With this method, we have achieved dye and DNA delivery in plant organs with curved surfaces.

Image-guided focused ultrasound-mediated molecular delivery to breast cancer in an animal model

Tumors become inoperable due to their size or location, making neoadjuvant chemotherapy the primary treatment. However, target tissue accumulation of anticancer agents is limited by the physical barriers of the tumor microenvironment. Low-intensity focused ultrasound (FUS) in combination with microbubble (MB) contrast agents can increase microvascular permeability and improve drug delivery to the target tissue after systemic administration. The goal of this research was to investigate image-guided FUS-mediated molecular delivery in volume space. Three-dimensional (3-D) FUS therapy functionality was implemented on a programmable ultrasound scanner (Vantage 256, Verasonics Inc.) equipped with a linear array for image guidance and a 128-element therapy transducer (HIFUPlex-06, Sonic Concepts). FUS treatment was performed on breast cancer-bearing female mice (N = 25). Animals were randomly divided into three groups, namely, 3-D FUS therapy, two-dimensional (2-D) FUS therapy, or sham (control) therapy. Immediately prior to the application of FUS therapy, animals received a slow bolus injection of MBs (Definity, Lantheus Medical Imaging Inc.) and near-infrared dye (IR-780, surrogate drug) for optical reporting and quantification of molecular delivery. Dye accumulation was monitored via in vivo optical imaging at 0, 1, 24, and 48 h (Pearl Trilogy, LI-COR). Following the 48 h time point, animals were humanely euthanized and tumors excised for ex vivo analyzes. Optical imaging results revealed that 3-D FUS therapy improved delivery of the IR-780 dye by 66.4% and 168.1% at 48 h compared to 2-D FUS (p = 0.18) and sham (p = 0.047) therapeutic strategies, respectively. Ex vivo analysis revealed similar trends. Overall, 3-D FUS therapy can improve accumulation of a surrogate drug throughout the entire target tumor burden after systemic administration.

Synthetic molecular motor activates drug delivery from polymersomes.

The design of stimuli-responsive systems in nanomedicine arises from the challenges associated with the unsolved needs of current molecular drug delivery. Here, we present a delivery system with high spatiotemporal control and tunable release profiles. The design is based on the combination of an hydrophobic synthetic molecular rotary motor and a PDMS-b-PMOXA diblock copolymer to create a responsive self-assembled system. The successful incorporation and selective activation by low-power visible light (λ = 430 nm, 6.9 mW) allowed to trigger the delivery of a fluorescent dye with high efficiencies (up to 75%). Moreover, we proved the ability to turn on and off the responsive behavior on demand over sequential cycles. Low concentrations of photoresponsive units (down to 1 mol% of molecular motor) are shown to effectively promote release. Our system was also tested under relevant physiological conditions using a lung cancer cell line and the encapsulation of an Food and Drug Administration (FDA)-approved drug. Similar levels of cell viability are observed compared to the free given drug showing the potential of our platform to deliver functional drugs on request with high efficiency. This work provides an important step for the application of synthetic molecular machines in the next generation of smart delivery systems.

Activating the delivery of a model drug to lipid membrane by encapsulation of cyclodextrin: Combined experimental and molecular docking studies

Drug delivery science is always an important topic as it studies the delivery of therapeutic payloads to the desired target cells without affecting the healthy tissues/cells, thus minimizing drug-induced toxicity. Aiming towards the targeted drug delivery, the present project deals with the delivery of a polarity-sensitive solvatochromic model drug, namely, salt of 8-anilinonaphthalene-1-sulphonic acid (ANSA) to the model bio-membrane (which mimic several aspects of the real cell membrane), more precisely at the lipid-water interface of L–α-Dipalmitoylphosphatidylcholine (DPPC) phospholipid. The drug delivery process has been activated through the binding of dye with cyclodextrin, acting as a drug transporter. Detailed steady-state and time-resolved spectroscopic studies including molecular docking analysis imply the targeted drug delivery of dye, ANSA, towards the lipid-water interface region of lipid bilayers through encapsulation within the cyclodextrin void. Stronger binding interaction of the dye with the lipid bilayers relative to β-cyclodextrin (β-CD) is the foremost reason for the targeted delivery. The present biophysical interaction studies of drug-lipid interaction, thus, may provide a cordial approach for drug formulation and drug delivery.

Microfluidic preparation of composite hydrogel microparticles for the staining of microalgal cells

The delivery of lipophilic dyes, such as BODIPY 505/515, to cells is often hindered by their low aqueous solubility, necessitating the use of organic solvents to facilitate the delivery, which unfortunately compromises the viability of the cells. In this work, we demonstrate the generation of novel composite hydrogel microparticles loaded with BODIPY 505/515, which can be used to deliver the dye to microalgal cells to stain the intracellular lipids. The microparticles were prepared by combining polymeric micelles with hydrogel technology to obtain microparticles of enhanced loading capacity. The generated hydrogel microparticles were tested by incubation with Phaeodactylum tricornutum algal cells. The cells were rapidly and successfully stained by the dye-containing microparticles, and their viability was not affected by the staining process. The method can also be used to stain other types of microalgal cells, such as Nannochloropsis gaditana cells. We therefore believe that this work offers a versatile and useful solution to important cell-staining problems in biotechnology.

Green synthesis of graphene-based metal nanocomposite for electro and photocatalytic activity; recent advancement and future prospective

The presence of pollutants in waste water is a demanding problem for human health. Investigations have been allocated to study the adsorptive behavior of graphene-based materials to remove pollutants from wastewater. Graphene (GO) due to its hydrophilicity, high surface area, and oxygenated functional groups, is an effective adsorbent for the removal of dyes and heavy metals from water. The disclosure of green synthesis opened the gateway for the economic productive methods. This article reveals the fabrication of graphene-based composite from aloe vera extract using a green method. The proposed mechanism of GO reduction via plant extract has also been mentioned in this work. The mechanism associated with the removal of dyes and heavy metals by graphene-based adsorbents and absorptive capacities of heavy metals has been discussed in detail. The toxicity of heavy metals has also been mentioned here. The Polyaromatic resonating system of GO develops significant π-π interactions with dyes whose base form comprises principally oxygenated functional groups. This review article illustrates a literature survey by classifying graphene-based composite with a global market value from 2010 to 2025 and also depicts a comparative study between green and chemical reduction methods. It presents state of art for the fabrication of GO with novel adsorbents such as metal, polymer, metal oxide and elastomers-based nanocomposites for the removal of pollutants. The current progress in the applications of graphene-based composites in antimicrobial, anticancer, drug delivery, and removal of dyes with photocatalytic efficacy of 73% is explored in this work. It gives a coherent overview of the green synthesis of graphene-based composite, various prospective for the fabrication of graphene, and their biotoxicity.

An integrated IRN-BWM-EDAS method for supplier selection in a textile industry

Like all other manufacturing industries, supplier selection also plays a pivotal role in a textile industry with respect to timely and cost-effective delivery of raw materials (cotton, yarn or fabric), chemicals and dyes, machineries, spare parts and other auxiliary parts/items. An appropriately selected supplier would help the textile industry in seamless production of final or semi-finished products leading to effective deployment of supply chain management concept. Due to involvement of many competing suppliers and a set of conflicting criteria, supplier selection is often treated as a typical multi-criteria decision making problem. The process of choosing the right supplier for a given item often becomes more difficult due to presence of both quantitative and qualitative evaluation criteria. In this paper, based on six most significant criteria, an attempt is put forward to integrate interval rough number (IRN) with best worst method (BWM) and evaluation based on distance from average solution (EDAS) method to solve a supplier selection problem for a textile industry. The application of IRN helps in expressing opinions of the decision makers with respect to relative importance of the considered criteria and performance of the suppliers against each of the criteria using rough boundary intervals under group decision making environment. Later, the criteria weights are determined using IRN-BWM and the alternative suppliers are ranked from the best to the worst employing IRN-EDAS method. An IRN Dombi weighted geometric averaging (IRNDWGA) technique is considered to aggregate the opinions of the decision makers. This integrated approach identifies alternative 3 as the most apposite supplier for the textile industry under consideration.

Mouthwash as a non-invasive method of indocyanine green delivery for near-infrared fluorescence dental imaging.

.Significance: X-ray imaging serves as the mainstream imaging in dentistry, but it involves risk of ionizing radiation.Aim: This study presents the feasibility of indocyanine green-assisted near-infrared fluorescence (ICG-NIRF) dental imaging with 785-nm NIR laser in the first (ICG-NIRF-I: 700 to 1000 nm) and second (ICG-NIRF-II: 1000 to 1700 nm) NIR wavelengths.Approach: Sprague Dawley rats with different postnatal days were used as animal models. ICG, as a fluorescence agent, was delivered to dental structures by subcutaneous injection (SC) and oral administration (OA).Results: For SC method, erupted and unerupted molars could be observed from ICG-NIRF images at a short imaging time (). ICG-NIRF-II could achieve a better image contrast in unerupted molars at 24 h after ICG injection. The OA could serve as a non-invasive method for ICG delivery; it could also cause the glow-in-dark effect in unerupted molars. For erupted molars, OA can be considered as mouthwash and exhibits outstanding performance for delivery of ICG dye; erupted molar structures could be observed at a short imaging time () and low ICG dose ().Conclusions: Overall, ICG-NIRF with mouthwash could perform in-vivo dental imaging in two NIR wavelengths at a short time and low ICG dose.

Immobilization of Methyl Orange and Methylene Blue within the Matrix of Charge-Imbalanced Amphoteric Nanogels and Study of Dye Release Kinetics as a Function of Temperature and Ionic Strength

Cross-linked polyampholyte nanogels consisting of neutral N-isopropylacrylamide (NIPAM), negatively charged sodium salt of 2-acrylamido-2-methylpropanesulfonate (AMPS), and positively charged (3-acryl-amidopropyltrimethylammonium chloride (APTAC) monomers were synthesized via conventional redox ini-tiated free radical copolymerization using N,N-methylenebis(acrylamide) (MBAA) as a cross-linking agent. The resulting nanogels were characterized by means of FTIR and 1H NMR spectroscopy, dynamic light scat-tering (DLS) and zeta-potential measurements. Surface morphology was analyzed using scanning electron microscopy. Due to the presence of thermally responsive NIPAM units and varying molar ratios of anionic (AMPS) and cationic (APTAC) units, the resulting nanogels were responsive to multiple stimuli in aqueous media and can be used for controlled delivery of dyes. Thus, the NIPAM90-APTAC7.5-AMPS2.5 nanogel with an excess of the cationic units was chosen for immobilization of the anionic dye, methyl orange (MO), whereas the NIPAM90-APTAC2.5-AMPS7.5 nanogel with an excess of the anionic units was chosen for immo-bilization of the cationic dye, methylene blue (MB). The release kinetics of the dyes from the nanogel was studied depending on the phase transition temperature and the salt content. Mechanism of the dye release from the nanogel matrix was determined using the Ritger-Peppas equation. Disappearance of the ionic con-tacts between the charged groups of the nanogels and the ionic dyes was suggested to be the main reason for the diffusion of the dyes through the dialysis membrane into the external solution.

The Impact of Bilayer Rigidity on the Release from Magnetoliposomes Vesicles Controlled by PEMFs.

Stimuli-sensitive nanocarriers have recently been developed as a powerful tool in biomedical applications such as drug delivery, detection, and gene transfer techniques. Among the external triggers investigated, low intensity magnetic fields represent a non-invasive way to remotely control the release of compounds from a magneto-sensitive carrier. Magnetoliposomes (MLs), i.e., liposomes entrapping magnetic nanoparticles (MNPs), are studied due to their capacity to transport hydrophobic and hydrophilic agents, their easy production, and due to the ability of MNPs to respond to a magnetic actuation determining the triggered release of the encapsulated compounds. Here we investigated the design and optimization of the MLs to obtain an efficient on-demand release of the transported compounds, due to the magneto-mechanical actuation induced by applying low-intensity pulsed electromagnetic fields (PEMFs). In particular we studied the effect of the bilayer packing on the ability of MLs, with oleic acid-coated MNPs encapsulated in the bilayer, to respond to PEMFs application. Three kinds of MLs are produced with an increasing rigidity of the bilayer, defined as Liquid Disorder, Liquid Order, and Gel MLs and the delivery of a hydrophilic dye (as a model drug) is investigated. Results demonstrate the efficacy of the magnetic trigger on high-ordered bilayers, which are unable to dampen the perturbation produced by MNPs motion.

Modulation of acoustofluidic parameters to assess effect on molecular loading in human T cells

T-cell therapies are rapidly emerging for treatment of cancer and other diseases but are limited by inefficient non-viral delivery methods. Acoustofluidic devices are in development to enhance non-viral delivery to cells. The effect of acoustofluidic parameters, such as channel geometry, on molecular loading in human T cells was assessed using 3D-printed acoustofluidic devices. Devices with rectilinear channels (1- and 2-mm diameters) were compared directly with concentric spiral channel geometries. Intracellular delivery of a fluorescent dye (calcein, 100 μg/ml) was evaluated in Jurkat T cells using flow cytometry after ultrasound treatment with cationic microbubbles (2.5% v/v). B-mode ultrasound pulses (2.5 MHz, 3.8 MPa output pressure) were generated by a P4-1 transducer on a Verasonics Vantage ultrasound system. Cell viability was assessed using propidum iodine staining (10 μg/ml). Intracellular molecular delivery was significantly enhanced with acoustofluidic treatment in each channel geometry, but treatment with the 1-mm concentric spiral geometry further enhanced delivery after acoustofluidic treatment compared to both 1- and 2-mm rectilinear channels (ANOVA p < 0.001, n = 6/group). These results indicate that 3D-printed acoustofluidic devices enhance molecular delivery to T cells, and channel geometry modulates intracellular loading efficiency. This approach may offer advantages to improve manufacturing of T cell therapies.

Sub-millimetre precision of drug delivery in the brain from ultrasound-triggered nanodroplets

Drug-loaded nanoscale cavitation agents, called nanodroplets, are an attractive solution to enhance and localize drug delivery, offering increased stability and prolonged half-life in circulation compared to microbubbles. However, the spatial precision with which drug can be released and delivered into brain tissue from such agents has not been directly mapped. Decafluorobutane lipid-shell droplets (206 +/− 6 nm) were loaded with a fluorescent blood-brain barrier (BBB)-penetrating dye (Nile Blue) and vaporized with ultrasound (1.66 MHz, 10 ms pulse length, 1 Hz pulse repetition frequency), generating transient echogenic microbubbles and delivering the encapsulated dye. The distribution and intensity of released fluorophore was mapped in a tissue-mimicking phantom, and in the brain of rats (Sprague Dawley, N = 4, n = 16). The release and distribution of dye was found to be pressure-dependent (0.2–3.5 MPa) and to occur only above the vaporization threshold of the nanodroplets (1.5 +/− 0.25 MPa in vitro, 2.4 +/− 0.05 MPa in vivo). Dye delivery was achieved with sub-millimetre spatial precision, covering an area of 0.4 to 1.5 mm in diameter, determined by the sonication pressure. The distribution and intensity of dye released at depth in the brain followed the axial pressure profile of the ultrasound beam. Nile Blue (354 Da, LogP 2.7) was compared to Nile Red (318 Da, LogP 3.8) and Quantum Dots (CdSe/ZnS, 5 nm diameter) to visualize the role of molecule size and lipophilicity in crossing the intact BBB following triggered release. Acoustic emissions were shown to predict the successful delivery of the BBB-penetrating dye and the extent of the distribution, demonstrating the theranostic capabilities of nanoscale droplets to precisely localize drug delivery in the brain.

Lithographically patterned micro-nozzles for controlling fluid flow profiles for drug delivery and in vitro imaging applications.

Precisely controlling delivery of drugs and other reagents is important for intravital microscopy studies. In this work, photolithographic integration of micro-nozzles onto a microfluidic platform was performed to tune the fluid flow profile and depth of penetration into biological tissue mimics. Performance characteristics were measured by correlating the flow rate through the device to the applied pressure and/or delivery of dyes into solution and agarose gel-based phantom tissue. From these results, the implementation of micro-nozzles was demonstrated to significantly improve the lateral dispersion of delivered fluid and increase the depth of penetration into phantom tissue.

Cross-linked Histone as a Nanocarrier for Gut Delivery of Hydrophobic Cargos.

Delivering hydrophobic molecules through the intestine can be challenging due to limited cargo solubility and the harsh biochemical environment of the stomach. Here, we show that a protein-based nanocarrier system based on the abundant protein histone and the natural cross-linker genipin can deliver hydrophobic cargos, such as dyes and therapeutic molecules, through the gastrointestinal tract. Using hydrophobic near-infrared dyes as model cargos, a panel of potential protein carriers was screened, and histone was identified as the one with the best loading capability. The resulting nanoparticles had a positive ζ potential and were mucoadhesive. Cross-linking of the amine-rich nanocarrier with genipin was particularly effective relative to other proteins and increased the stability of the system during incubation with pepsin. Cross-linking was required for successful delivery of a hydrophobic dye to the colon of mice after oral gavage. To assess the platform for therapeutic delivery, another hydrophobic model compound, curcumin, was delivered using cross-linked histone nanoparticles in a murine colitis model and significantly alleviated the disease. Taken together, these results demonstrate that histone is a cationic, mucoadhesive, and cross-linkable protein nanocarrier that can be considered for oral delivery.

A Microneedles Balloon Catheter for Endovascular Drug Delivery

AbstractDisorders of the inner parts of blood vessels have been significant triggers of cardiovascular diseases (CVDs). Different interventional methods have been employed, from complex surgeries to balloon angioplasty techniques to open the narrowed blood vessels. However, CVDs continue to be the lead cause of death in the world. Delivering a therapeutic agent directly to the inner wall of affected blood vessels can be a transformative step toward a better treatment option. To open the door for such an approach, a catheter delivery system is developed based on a conventional balloon catheter where a fluidic channel and microneedles (MNs) are integrated on top of it. This enables precise and localized delivery of therapeutics directly into vessel walls. Customizable MNs are fabricated using a high‐resolution 3D printing technique where MN's height ranges from 100 to 350 µm. The MNs penetration into a synthetic vascular model is investigated with a computerized tomography scan. Ex vivo tests on rabbit aorta confirm the MN‐upgraded balloon catheter's performance on real tissue. Delivery of fluorescent dye is accomplished by injecting it through the fluidic channel and MNs into the aortic tissue. The dye is observed at up to 180 µm of depth, confirming site‐specific endovascular delivery.

Method of intra-arterial drug administration in a rat: Sex based optimization of infusion rate

BackgroundEndovascular thrombectomy is the process of removing a blood clot and re-establishing blood flow in patients with emergent large vessel occlusion. The technique provides an opportunity to deliver therapeutics directly to the site of injury. The intra-arterial (IA) route of drug administration in the mouse was developed to bridge the gap between animal stroke treatments and clinical stroke therapy. Here, we adapted the IA method for use in rats, by investigating various flow rates to optimize the IA injection through the internal carotid artery (ICA). MethodsMale and female Sprague-Dawley rats (∼4 months of age) were subjected to placement of micro-angio tubing at the bifurcation of the common carotid artery for injection into the ICA. We evaluated a range of infusion rates of carbon black ink and its vascular distribution within the brain. ResultsOptimal injection rates in males was 4−6 μl/min and 2−4 μl/min in females. The IA injection using these sex-specific rates resulted in appropriate limited dye delivery to only the ipsilateral region of the brain, without inducing a subarachnoid hemorrhage. ConclusionUpon adapting the IA administration model to rats, it was determined that the rate of infusion varied between males and females. This variability is an important consideration for studies utilizing both sexes, such as in ischemic stroke studies.

Nanogels as Antifungal‐Drug Delivery System Against Aspergillus Fumigatus

Aspergillus fumigatus is the opportunistic fungus responsible for a variety of serious and often lethal diseases of immunocompromised patients, such as invasive aspergillosis, aspergilloma, and allergic bronchopulmonary aspergillosis. Therapeutic options for such fungal infections are limited due to the high toxicity of currently available drugs. Herein, the potency of nanogels (NGs) is assessed for uptake and delivery of antifungal therapeutics. Therefore, poly(glycidol)‐based NGs are prepared by surfactant‐free inverse nanoprecipitation. Uptake studies conducted with fluorescently labeled particles demonstrate internalization by fungi in their hyphal form. In addition, loading with both amphiphilic and hydrophobic fluorescent dyes as model drugs show efficient delivery of the fluorescent dyes into the fungus. Finally, particles are loaded with the antifungal drug itraconazole by soaking lyophilized NGs in the drug solution (breathing‐in method). Efficient delivery of the drug by nanoprecipitated NGs, improved fungicidal activity, and reduced side effects as compared with the drug itself are shown.