The Impact of PEGylation on Cellular Uptake and In Vivo Biodistribution of Gold Nanoparticle MRI Contrast Agents.

Gold nanoparticles (GNPs) have immense potential in biomedicine, but understanding their interactions with serum proteins is crucial as it could change their biological profile due to the formation of a protein corona, which could then affect their ultimate biodistribution in the body. Grafting GNPs with polyethylene glycol (PEG) is a widely used practice in research in order to decrease opsonization of the particles by serum proteins and to decrease particle uptake by the mononuclear phagocyte system. We investigated the impact of PEGylation on the formation of protein coronae and the subsequent uptake by macrophages and MDA-MB-231 cancer cells. Furthermore, we investigated the in vivo biodistribution in xenograft tumor-bearing mice using a library of 4 and 10 nm GNPs conjugated with a gadolinium chelate as MRI contrast agent, cancer-targeting aptamer AS1411 (or CRO control oligonucleotide), and with or without PEG molecules of different molecular weight (Mw: 1, 2, and 5 kDa). In vitro results showed that PEG failed to decrease the adsorption of proteins; moreover, the cellular uptake by macrophage cells was contingent on the different configurations of the aptamers and the length of the PEG chain. In vivo biodistribution studies showed that PEG increased the uptake by tumor cells for some GNPs, albeit it did not decrease the uptake of GNPs by macrophage-rich organs.

Optimization of Tumor Targeting Gold Nanoparticles for Glioblastoma Applications.

Glioblastoma brain tumors represent an aggressive form of gliomas that is hallmarked by being extremely invasive and aggressive due to intra and inter-tumoral heterogeneity. This complex tumor microenvironment makes even the newer advancements in glioblastoma treatment less effective long term. In developing newer treatment technologies against glioblastoma, one should tailor the treatment to the tumor microenvironment, thus allowing for a more robust and sustained anti-glioblastoma effect. Here, we present a novel gold nanoparticle therapy explicitly designed for bioactivity against glioblastoma representing U87MG cell lines. We employ standard conjugation techniques to create oligonucleotide-coated gold nanoparticles exhibiting strong anti-glioblastoma behavior and optimize their design to maximize bioactivity against glioblastoma. Resulting nanotherapies are therapy specific and show upwards of 75% inhibition in metabolic and proliferative activity with stark effects on cellular morphology. Ultimately, these gold nanotherapies are a good base for designing more multi-targeted approaches to fighting against glioblastoma.

DNA-mediated hierarchical organization of gold nanoprisms into 3D aggregates and their application in surface-enhanced Raman scattering.

Colloidal crystallization using DNA provides a robust method for fabricating highly programmable nanoparticle superstructures with collective plasmonic properties. Here, we report on the DNA-guided fabrication of 3D plasmonic aggregates from polydisperse gold nanoprisms. We first construct 1D crystals via DNA-induced and shape-directed face-to-face assembly of anisotropic gold nanoprisms. Using the near-Tm thermal annealing approach that promotes long-range DNA-induced interaction and ordering, we then assemble 1D nanoprism crystals into a 3D nanoprism aggregate that exhibits a polycrystalline morphology with nanoscale ordering and microscale dimensions. The presence of closely packed nanoprism arrays over a large area gives rise to strong near-field plasmonic coupling and generates a high density of plasmonic hot spots within the 3D nanoprism aggregates that exhibit excellent surface-enhanced Raman scattering performance. The plasmonic 3D nanoprism aggregates demonstrate significant SERS enhancement (<106), and low detection limits (10-9M) with good sample-to-sample reproducibility (CV ∼ only 5.6%) for SERS analysis of the probe molecule, methylene blue. These findings highlight the potential of 3D anisotropic nanoparticle aggregates as functional plasmonic nanoarchitectures that could find applications in sensing, photonics, optoelectronics and lasing.

Adsorption Properties and Electron-transfer Rates of a Redox Probe at Different Interfaces of an Immunoassay Assembled on an Electro-active Photonic Platform.

Physical and chemical properties of a redox protein adsorbed to different interfaces of a multilayer immunoassay assembly were studied using a single-mode, electro-active, integrated optical waveguide (SM-EA-IOW) platform. For each interface of the immunoassay assembly (indium tin oxide, 3-aminopropyl triethoxysilane, recombinant protein G, antibody, and bovine serum albumin) the surface density, the adsorption kinetics, and the electron-transfer rate of bound species of the redox-active cytochrome c (Cyt-C) protein were accurately quantified at very low surface concentrations of redox species (from 0.4 to 4% of a full monolayer) using a highly sensitive optical impedance spectroscopy (OIS) technique based on measurements obtained with the SM-EA-IOW platform. The technique is shown here to provide quantitative insights into an important immunoassay assembly for characterization and understanding of the mechanisms of electron transfer rate, the affinity strength of molecular binding, and the associated bio-selectivity. Such methodology and acquired knowledge are crucial for the development of novel and advanced immuno-biosensors.

Sustained dasatinib treatment prevents early fibrotic changes following ocular trauma.

PURPOSE: Posterior ocular trauma and the subsequent fibrotic retinal complication termed proliferative vitreoretinopathy (PVR) are leading causes of blindness in children and young adults. A previous study suggested that changes occurring within the first month post-trauma can lead to development of PVR later. The aim of this study was to examine the effect of dasatinib, a tyrosine kinase inhibitor clinically used to treat chronic myeloid leukemia, on fibrotic changes occurring within the first month following ocular trauma. METHODS: A previously established swine ocular trauma model that mimics both contusion and penetrating injuries was used. Dasatinib was administered on days 4 and 18 post-trauma via intravitreal injection of either bolus solution or suspension of a sustained release system incorporated in biodegradable poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Animals were followed up to day 32, and the development of traction full-thickness fold in the posterior retina was assessed. RESULTS: A full-thickness retinal fold extending from the wound site developed in 3 out of 4 control eyes injected with PLGA nanoparticles alone at 1 month. Administration of dasatinib solution had little preventative effect with 6 out of 7 eyes developing a fold. In contrast, dasatinib-incorporated PLGA nanoparticle injection significantly reduced the incidence of fold to 1 out of 10 eyes. CONCLUSIONS: Injection of dasatinib-incorporated PLGA significantly reduced early fibrotic retinal changes which eventually lead to PVR following posterior ocular trauma. Thus, our sustained dasatinib release system can potentially be used to both prevent and/or broaden the surgical treatment window for PVR.

Positive Impact of Education Class for Parents with Adverse Childhood Experiences on Child Behavior.

BACKGROUND: There is a need for community-based parent education programs that strengthen the parent-child relationship and mitigate the negative impact of parental adverse childhood experiences (ACEs) on child social-emotional development. OBJECTIVE: To examine whether a community-based parent education program can improve children's social-emotional development. METHODS: This was a prospective observational study of a series of community education parenting classes in Rochester, Minnesota. Group classes were delivered weekly for three months. Classes used Dr. Becky Bailey's Conscious Discipline Program. Parents of children ages 2 to 5 years and identified as at risk of poor social-emotional outcomes based on the Ages and Stages Questionnaire: Social-Emotional 2 (ASQ:SE2) score were eligible to participate. RESULTS: There were 39 child-parent dyads who enrolled. Parental ACEs scores ranged from 0 to 6 with a median of 1.5 (interquartile range, 0-3, N = 34). In the 33 children with both before and after ASQ:SE2 tests available, there was a significant decrease in the post-ASQ:SE2 score compared with the pre-ASQ:SE2 score (mean difference, -30.3; 95% confidence interval, CI -42.2 to -18.4; p < 0.001) where lower scores are associated with less social-emotional impairment. There was no significant association in the change of pre-post ASQ:SE2 scores as parents' ACEs scores increased (estimated slope, 3.1; 95% CI -3.7 to 9.9; p = 0.36). CONCLUSIONS: Community-based, parent education interventions can improve child social-emotional development. This program using Dr. Becky Bailey's Conscious Discipline Program improved ASQ-SE scores, regardless of parental ACEs exposure.

DNA-induced assembly of gold nanoprisms and polystyrene beads into 3D plasmonic SERS substrates.

The utilization of nanoparticle-polymer bead hybrid nanostructures as a SERS substrate depends on the control of the deposition, density, and distribution of nanoparticles on the bead surface. Here we demonstrate the fabrication of a large area SERS substate via a two- step DNA mediated assembly of gold nanoprisms and polystyrene (PS) beads into a large ensemble of beads that are densely coated with nanoprisms. First, nanoprisms are loaded on PS beads through DNA hybridization. The close packed arrangement of anisotropic nanoprisms in different orientations on a bead surface results in a plasmonic substrate with a variable nanogap size ranging 1-20 nm. Nanoprisms-coated beads are then assembled into a large stack or aggregate of beads using a DNA-induced crystallization approach. Each aggregate consists of 20-50 nanoprisms-coated beads, leading to the formation a large area of three-dimensional SERS substrate with a high-density of hot spots for SERS enhancement. An excellent enhancement factor (EF) of [Formula: see text] and a very high detection sensitivity (up to 10-10 M) are observed for the analysis of a probe molecule (Methylene blue) using the SERS substrate.

Radiation-induced curcumin release from curcumin-chitosan polymer films.

The probability of human exposure to damaging radiation is increased in activities associated with long-term space flight, medical radiation therapies, and responses to nuclear accidents. However, the development of responsive countermeasures to combat radiation damage to biological tissue is lagging behind rates of human exposure. Herein, we report a radiation-responsive drug delivery system that releases doses of curcumin from a chitosan polymer/film in response to low level gamma radiation exposure. As a fibrous chitosan-curcumin polymer, 1 Gy gamma irradiation (137Cs) released 5 ± 1% of conjugated curcumin, while 6 Gy exposure releases 98 ± 1% of conjugated curcumin. The same polymer was formed into a film through solvent casting. The films showed similar, albeit attenuated behavior in water (100% released) and isopropyl alcohol (32% released) with statistically significant drug release following 2 Gy irradiation. ATR FT-IR studies confirmed glycosidic bond cleavage in the chitosan-curcumin polymer in response to gamma radiation exposure. Similar behavior was noted upon exposure of the polymer to 20 cGy (1 GeV amu-1, at 20 cGy min-1) high linear energy transfer (LET) 56Fe radiation based on FTIR studies. Density Functional Theory calculations indicate homolytic bond scission as the primary mechanism for polymer disintegration upon radiation exposure. Films did not change in thickness during the course of radiation exposure. The successful demonstration of radiation-triggered drug release may lead to new classes of radio-protective platforms for developing countermeasures to biological damage from ionizing radiation.

Targeted Gold Nanoparticle⁻Oligonucleotide Contrast Agents in Combination with a New Local Voxel-Wise MRI Analysis Algorithm for In Vitro Imaging of Triple-Negative Breast Cancer.

Gold nanoparticles (GNPs) have tremendous potential as cancer-targeted contrast agents for diagnostic imaging. The ability to modify the particle surface with both disease-targeting molecules (such as the cancer-specific aptamer AS1411) and contrast agents (such as the gadolinium chelate Gd(III)-DO3A-SH) enables tailoring the particles for specific cancer-imaging and diagnosis. While the amount of image contrast generated by nanoparticle contrast agents is often low, it can be augmented with the assistance of computer image analysis algorithms. In this work, the ability of cancer-targeted gold nanoparticle-oligonucleotide conjugates to distinguish between malignant (MDA-MB-231) and healthy cells (MCF-10A) is tested using a T1-weighted image analysis algorithm based on three-dimensional, deformable model-based segmentation to extract the Volume of Interest (VOI). The gold nanoparticle/algorithm tandem was tested using contrast agent GNP-Gd(III)-DO3A-SH-AS1411) and nontargeted c-rich oligonucleotide (CRO) analogs and control (CTR) counterparts (GNP-Gd(III)-DO3A-SH-CRO/CTR) via in vitro studies. Remarkably, the cancer cells were notably distinguished from the nonmalignant cells, especially at nanomolar contrast agent concentrations. The T1-weighted image analysis algorithm provided similar results to the industry standard Varian software interface (VNMRJ) analysis of T1 maps at micromolar contrast agent concentrations, in which the VNMRJ produced a 19.5% better MRI contrast enhancement. However, our algorithm provided more sensitive and consistent results at nanomolar contrast agent concentrations, where our algorithm produced ~500% better MRI contrast enhancement.

Detection of influenza virus by electrochemical surface plasmon resonance under potential modulation.

In this study we report the development of a novel viral pathogen immunosensor technology based on the electrochemical modulation of the optical signal from a surface plasmon wave interacting with a redox dye reporter. The device is formed by incorporating a sandwich immunoassay onto the surface of a plasmonic device mounted in a micro-electrochemical flow cell, where it is functionalized with a monoclonal antibody aimed to a specific target pathogen antigen. Once the target antigen is bound to the surface, it promotes the capturing of a secondary polyclonal antibody that has been conjugated with a redox-active methylene blue dye. The methylene blue displays a reversible change in the complex refractive index throughout a reduction-oxidation transition, which generates an optical signal that can be electrochemically modulated and detected at high sensitivity. For proof-of-principle measurements, we have targeted the hemagglutinin protein from the H5N1 avian influenza A virus to demonstrate the capabilities of our device for detection and quantification of a critical influenza antigen. Our experimental results of the EC-SPR-based immunosensor under potential modulation showed a 300 pM limit of detection for the H5N1 antigen.

Development of a goat model for evaluation of withaferin A: Cervical implants for the treatment of cervical intraepithelial neoplasia.

Cervical cancer is caused by human papillomavirus (HPV). The disease develops over many years through a series of precancerous lesions. Cervical cancer can be prevented by HPV-vaccination, screening and treatment of precancer before development of cervical cancer. The treatment of high-grade cervical dysplasia (CIN 2+) has traditionally been by cervical conization. Surgical procedures are associated with increased risk of undesirable side effects including bleeding, infection, scarring (stenosis), infertility and complications in later pregnancies. An inexpensive, non-invasive method of delivering therapeutics locally will be favorable to treat precancerous cervical lesions without damaging healthy tissue. The feasibility and safety of a sustained, continuous drug-releasing cervical polymeric implant for use in clinical trials was studied using a large animal model. The goat (Capra hircus), non-pregnant adult female Boer goats, was chosen due to similarities in cervical dimensions to the human. Estrus was induced with progesterone CIDR® vaginal implants for 14days followed by the administration of chorionic gonadotropins 48h prior to removal of the progesterone implants to relax the cervix to allow for the placement of the cervical implant. Cervical implants, containing 2% and 4% withaferin A (WFA), with 8 coats of blank polymer, provided sustained release for a long duration and were used for the animal study. The 'mushroom'-shaped cervical polymeric implant, originally designed for women required redesigning to be accommodated within the goat cervix. The cervical implants were well tolerated by the animals with no obvious evidence of discomfort, systemic or local inflammation or toxicity. In addition, we developed a new method to analyze tissue WFA levels by solvent extractions and LS/MS-MS. WFA was found to be localized to the target and adjacent tissues with 12-16ng WFA/g tissue, with essentially no detectable WFA in distant tissues. This study suggests that the goat is a good large animal model for the future development and evaluation of therapeutic efficacy of continuous local drug delivery by cervical polymeric implants to treat precancerous cervical lesions.

Influenza virus immunosensor with an electro-active optical waveguide under potential modulation.

Here we report the development of a novel immunosensor-based strategy for label-free detection of viral pathogens by incorporating a sandwich bioassay onto a single-mode, electro-active, integrated optical waveguide (EA-IOW). Our strategy begins with the functionalization of the electro-active waveguide surface with a capture antibody aimed at a specific virus antigen. Once the target antigen is bound to the photonic interface, it promotes the binding of a secondary antibody that has been labeled with a methylene blue (MB) dye. The MB is a redox-active probe whose optical absorption can be electrically modulated and interrogated with high sensitivity by a propagating waveguide mode. In this effort, we have targeted the hemagglutinin (HA) protein from the H5N1 avian influenza A virus to demonstrate the capabilities of the EA-IOW device for detection and quantification of an important antigen. Our initial results for the HA H5N1 influenza virus show a remarkable limit of detection in the pico-molar range.

G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms.

BACKGROUND: AS1411 is a 26-mer G-rich DNA oligonucleotide that forms a variety of G-quadruplex structures. It was identified based on its cancer-selective antiproliferative activity and subsequently determined to be an aptamer to nucleolin, a multifunctional protein that preferentially binds quadruplex nucleic acids and which is present at high levels on the surface of cancer cells. AS1411 has exceptionally efficient cellular internalization compared to non-quadruplex DNA sequences. SCOPE OF REVIEW: Recent developments related to AS1411 will be examined, with a focus on its use for targeted delivery of therapeutic and imaging agents. MAJOR CONCLUSIONS: Numerous research groups have used AS1411 as a targeting agent to deliver nanoparticles, oligonucleotides, and small molecules into cancer cells. Studies in animal models have demonstrated that AS1411-linked materials can accumulate selectively in tumors following systemic administration. The mechanism underlying the cancer-targeting ability of AS1411 is not completely understood, but recent studies suggest a model that involves: (1) initial uptake by macropinocytosis, a form of endocytosis prevalent in cancer cells; (2) stimulation of macropinocytosis by a nucleolin-dependent mechanism resulting in further uptake; and (3) disruption of nucleolin-mediated trafficking and efflux leading to cargoes becoming trapped inside cancer cells. SIGNIFICANCE: Human trials have indicated that AS1411 is safe and can induce durable remissions in a few patients, but new strategies are needed to maximize its clinical impact. A better understanding of the mechanisms by which AS1411 targets and kills cancer cells may hasten the development of promising technologies using AS1411-linked nanoparticles or conjugates for cancer-targeted therapy and imaging. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

Release-Modulated Antioxidant Activity of a Composite Curcumin-Chitosan Polymer.

Curcumin is known to have immense therapeutic potential but is hindered by poor solubility and rapid degradation in solution. To overcome these shortcomings, curcumin has been conjugated to chitosan through a pendant glutaric anhydride linker using amide bond coupling chemistry. The hybrid polymer has been characterized by UV-visible, fluorescence, and infrared spectroscopies as well as zeta potential measurements and SEM imaging. The conjugation reactivity was confirmed through gel permeation chromatography and quantification of unconjugated curcumin. An analogous reaction of curcumin with glucosamine, a small molecule analogue for chitosan, was performed and the purified product characterized by mass spectrometry, UV-visible, fluorescence, and infrared spectroscopies. Conjugation of curcumin to chitosan has greatly improved curcumin aqueous solubility and stability, with no significant curcumin degradation detected after one month in solution. The absorbance and fluorescence properties of curcumin are minimally perturbed (λmax shifts of 2 and 5 nm, respectively) by the conjugation reaction. This conjugation strategy required use of one out of two curcumin phenols (one of the main antioxidant functional groups) for covalent linkage to chitosan, thus temporarily attenuating its antioxidant capacity. Hydrolysis-based release of curcumin from the polymer, however, is accompanied by full restoration of curcumin's antioxidant potential. Antioxidant assays show that curcumin radical scavenging potential is reduced by 40% after conjugation, but that full antioxidant potential is restored upon hydrolytic release from chitosan. Release studies show that curcumin is released over 19 days from the polymer and maintains a concentration of 0.23 ± 0.12 µM curcumin/mg polymer/mL solution based on 1% curcumin loading on the polymer. Release studies in the presence of carbonic anhydrase, an enzyme with known phenolic esterase activity, show no significant difference from nonenzymatic release studies, implying that simple ester hydrolysis is the dominant release mechanism. Conjugation of curcumin to chitosan through a phenol ester modification provides improved stability and solubility to curcumin, with ester hydrolysis restoring the full antioxidant potential of curcumin.

AS1411-conjugated gold nanospheres and their potential for breast cancer therapy.

AS1411 is a quadruplex-forming DNA oligonucleotide that functions as an aptamer to target nucleolin, a protein present on the surface of cancer cells. Clinical trials of AS1411 have indicated it is well tolerated with evidence of therapeutic activity, but improved pharmacology and potency may be required for optimal efficacy. In this report, we describe how conjugating AS1411 to 5 nm gold nanospheres influences its activities in vitro and in vivo. We find that the AS1411-linked gold nanospheres (AS1411-GNS) are stable in aqueous and serum-containing solutions. Compared to unconjugated AS1411 or GNS linked to control oligonucleotides, AS1411-GNS have superior cellular uptake and markedly increased antiproliferative/cytotoxic effects. Similar to AS1411, AS1411-GNS show selectivity for cancer cells compared to non-malignant cells. In a mouse model of breast cancer, systemic administration of AS1411-GNS could completely inhibit tumor growth with no signs of toxicity. These results suggest AS1411-GNS are promising candidates for clinical translation.

Magnetic nanoparticle-supported lipid bilayers for drug delivery.

Magnetic nanoparticle-supported lipid bilayers (SLBs) constructed around core-shell Fe3O4-SiO2 nanoparticles (SNPs) were prepared and evaluated as potential drug carriers. We describe how an oxime ether lipid can be mixed with SNPs to produce lipid-particle assemblies with highly positive ζ potential. To demonstrate the potential of the resultant cationic SLBs, the particles were loaded with either the anticancer drug doxorubicin or an amphiphilic analogue, prepared to facilitate integration into the supported lipid bilayer, and then examined in studies against MCF-7 breast cancer cells. The assemblies were rapidly internalized and exhibited higher toxicity than treatments with doxorubicin alone. The magnetic SLBs were also shown to increase the efficacy of unmodified doxorubicin.

A high yield, one-pot dialysis-based process for self-assembly of near infrared absorbing gold nanoparticles.

HYPOTHESIS: A facile, dialysis-based synthesis of stable near infrared (nIR) absorbing plasmonic gold nanoparticles (λmax=650-1000 nm) will increase the yield of nIR particles and reduce the amount of gold colloid contaminant in the product mixture. EXPERIMENTS: Chloroauric acid and sodium thiosulfate were reacted using a dialysis membrane as a reaction vessel. Product yield and composition was determined and compared to traditional synthesis methods. The product particle distribution, yield, and partitioning of gold between dispersed product and membrane-adsorbed gold were determined. FINDINGS: The synthesis results in polydisperse particle suspensions comprised of 70% spheroid-like particles, 27% triangular plates, and 3% rod-like structures with a 3% batch-to-batch variation and a prominent nIR absorption band with λmax=650-1000 nm. The amount of small gold colloid (λmax=530 nm; d<10 nm) in the isolated product was reduced by 96% compared to traditional methods. Additionally, 91.1% of the gold starting material is retained in the solution-based nanoparticle mixture while 8.2% is found on the dialysis membrane. The synthesis results in a quality ratio (QR=Abs(nIR)/Abs(530)) of 1.7-2.4 (twice that of previous techniques) and 14.3 times greater OD∗ml yield of the nIR-absorbing nanoparticle fraction.

Enhanced drug delivery via hyperthermal membrane disruption using targeted gold nanoparticles with PEGylated Protein-G as a cofactor.

Gold nanoparticles (GNPs) with near infrared (NIR) plasmon resonance have been promisingly used in photothermal cancer therapy as a less invasive treatment. Recombinant Protein-G (ProG) was PEGylated to act as a cofactor to immobilize immunoglobulins (IgGs) on GNPs by the Fc region, resulting in optimal orientation of IgGs for efficient cancer targeting. In-vitro studies showed that HER-2 overexpressing breast cancer cells, SK-BR-3, were efficiently targeted and ablated at a laser power of 900 J/cm(2) (5 W/cm(2) for 3 min). However, as a means of enhancing treatment efficacy by increasing cellular sensitivity to chemotherapeutic agents, we showed that GNP exposure to lower power laser resulted in small disruptions of cell membrane due to localized hyperthermia. This did not lead to cell death but provided a mechanism for killing cancer cells by providing enhanced uptake of drug molecules thus leading to a new avenue for hyperthermia-anticancer drug combined cancer therapeutics. FROM THE CLINICAL EDITOR: PEGylated recombinant Protein-G was used as a cofactor to optimize the orientation of IgGs providing "target seeking" properties to gold nanoparticles used in photothermal cancer therapy. The system demonstrated excellent properties in cancer therapy, with the hope and expectation of future clinical translation.

Curcumin encapsulation in submicrometer spray-dried chitosan/Tween 20 particles.

Optimal curcumin delivery for medicinal applications requires a drug delivery system that both solubilizes curcumin and prevents degradation. To achieve this, curcumin has been encapsulated in submicrometer chitosan/Tween 20 particles via a benchtop spray-drying process. Spray-drying parameters have been optimized using a Taguchi statistical approach to minimize particle size and to favor spheroid particles with smooth surfaces, as evaluated with scanning electron microscopy (SEM) imaging. Nearly spherical particles with 285 ± 30 nm diameter and 1.21 axial ratio were achieved. Inclusion of curcumin in the spray-drying solution results in complete encapsulation of curcumin within the chitosan/Tween 20 particles. Release studies confirm that curcumin can be released completely from the particles over a 2 h period.