Differences In Particle Morphology Research Articles

High Performance of Porous, Hierarchically Structured P2‐Na0.6Al0.11 − xNi0.22 − yFex + yMn0.66O2 Cathode Materials

AbstractSodium‐ion‐batteries (SIB) are a low‐cost alternative to currently used lithium‐ion batteries (LIB) but suffer from poor cycling stability. Spray drying provides porous, hierarchically structured particles of cathode active material (CAM) in large amounts, suitable for up‐scaling. Changing the chemical composition of the Na0.6Al0.11 − xNi0.22 − yFex + yMn0.66O2 layered oxides under identical synthesis conditions lead to differences in particle morphology, conductivities, sodium vacancy ordering, and phase transition, therefore influencing the electrochemical performance via several mechanisms. Here, a broad overview on these changes for samples with variable nickel and iron content is presented. With increasing iron content, the particle porosity is reduced and lower initial capacity is received for most cycling windows. Substituting half of the original Ni amount with Fe still leads to high capacities and improved cycling stability. The influence of Al as electrochemically inactive element becomes visible in stabilized cycling stability as well.

Solution-Based Synthesis of Cathode Materials for Lithium Ion Batteries

Electrochemical energy storage is expected to make an important contribution to combating global climate change, e.g. via electric vehicles and stationary storage. Currently, lithium-ion batteries are the most prominent candidate for rechargeable batteries to be used in this respect. However, performance of lithium-ion batteries is strongly influenced by the active material at the cathode side, which is often a complex multi-metal oxide. Such a material's properties are dictated by the fabrication method. The design of an appropriate synthesis strategy is then logically also aimed at optimal material properties. However, the design strategy should also take into account green chemistry principles, such as atom economy and energy efficiency. Solution-based routes towards (multi)metal oxide synthesis provide a large diversity of routes and therefore a strong versatility in their design. In this contribution, two groups of routes will be discussed: aqueous solution-gel and coprecipitation routes. The aqueous solution-gel route encompasses three stages: precursor solution synthesis, in which the metal ions are stabilized by complexation with carboxylate ligands, gelation to form an amorphous precursor gel in which the metal ions are homogeneously mixed, and decomposition into the final metal oxide. In this route, precipitation is to be avoided, since it would introduce inhomogeneities. In contrast, the coprecipitation route is entirely based on the formation of insoluble solid precipitates, which can be further transformed in a solid state reaction into lithiated compounds. Whereas solution-gel is ideally suited for complex metal oxides with a large number of metal ions, coprecipitation of many different metal ions at the same time can be challenging. On the other hand, the atom efficiency of the latter can be very high which is attractive for upscaling. Certainly, both of these routes have a high versatility because of the flexibility in compositions (starting products, solvents, ...) and conditions (temperature, time, ...) during the synthesis.In this presentation, an overview will be given of the application of these synthesis routes to the synthesis and/ or surface modification of various cathode materials for lithium ion batteries, which are of general interest and are ranging from Ni-rich compositions of NMC (NMC622), to lithium manganese rich NMC and to Co-free compositions such as LNMO and Li rich LMO. First, the classic NMC 622 is surface modified by a TiOx via a sol-gel route, leading to the formation of core-shell structured particles. The presence of TiOx improved the rate performance and electronic conductivity of the cathode material, and led to a higher initial coulombic efficiency and lower ageing rates in full cells with LTO. Furthermore, layered Li-rich/Mn-rich (LMR-)NMC, which is interesting because of its remarkably high specific discharge capacity was synthesized by two different routes, solution-gel and coprecipitation. It was shown that the solution-gel material in this case had a retarded voltage fade but larger capacity fade than the coprecipitated material. This was correlated to differences in particle morphology and the presence of Ni-enriched spinel-type surface layer. Furthermore, the effect of Sn4+ substitution in the LMR-NMC was investigated. The solubility of Sn4+ substituting for Mn4+ turned out to be a limiting factor here, and could not prevent the voltage fade sufficiently. Finally, we turned to Co-free cathode compositions. LiNi0.5Mn1.5O4-delta was prepared by an aqueous solution-gel route, which allowed to tune the particle size (a few µm versus 70 µm) and morphology. This led to optimized initial discharge capacity and its retention. Finally, Ti4+ substituted Li2MnO3 was synthesized as well via an aqueous solution-gel method. The substitution was shown to improve the structural stability, and galvanostatic cycling hinted at a delayed oxygen release during the first 10 cycles, however, followed by pronounced oxygen redox activity.In conclusion, solution-based routes are highly versatile and provide many opportunities to synthesize cathode materials for lithium ion batteries.

Influence of different raw materials on the preparation of single-crystal LiNi0.5Mn1.5O4 by sol-gel method

Recently, due to the escalating cost of cobalt, there has been a growing interest in the LiNi0.5Mn1.5O4 (LNMO) cathode material, prompting efforts to enhance its performance in various aspects. However, there is a lack of research regarding the influence of raw materials used in the sol-gel method for LNMO preparation on the properties of the resulting product. In this study, we employed acetates, chlorides, and nitrates as raw materials and utilized a simple sol-gel approach to synthesize three types of single-crystal LNMO particles. Characterization of the material structures of these three samples revealed that LNMO prepared from acetates exhibited the highest concentration of oxygen vacancies (OVs) and demonstrated a more disordered structure, as well as better high-temperature stability. Scanning electron microscopy observations also indicated distinct differences in particle morphologies among samples prepared from different raw materials. The LNMO sample synthesized from acetates showed exceptional electrochemical performance. It achieved an initial coulombic efficiency of 85.62 % and a specific capacity of 111.19 mA h g–1, retaining 93.28 % of its capacity after 500 cycles at a 1 C rate.

Feasibility of the preparation of cochleate suspensions from naturally derived phosphatidylserines.

Cochleates are cylindrical particles composed of dehydrated phospholipid bilayers. They are typically prepared by addition of calcium ions to vesicles composed of negatively charged phospholipids such as phosphatidylserines (PS). Due to their high physical and chemical stability, they provide an interesting alternative over other lipid-based drug formulations for example to improve oral bioavailability or to obtain a parenteral sustained-release formulation. In the present study, the feasibility to prepare cochleate suspensions from soy lecithin-derived phosphatidylserines (SPS) was investigated and compared to the "gold standard" dioleoyl-phosphatidylserine (DOPS) cochleates. The SPS lipids covered a large range of purities between 53 and >96% and computer-controlled mixing was evaluated for the preparation of the cochleate suspensions. Electron microscopic investigations were combined with small-angle x-ray diffraction (SAXD) and Laurdan generalized polarization (GP) analysis to characterize particle structure and lipid organization. Despite some differences in particle morphology, cochleate suspensions with similar internal lipid structure as DOPS cochleates could be prepared from SPS with high headgroup purity (≥96%). Suspensions prepared from SPS with lower purity still revealed a remarkably high degree of lipid dehydration and well-organized lamellar structure. However, the particle shape was less defined, and the typical cochleate cylinders could only be detected in suspensions prepared with higher amount of calcium ions. Finally, the study proves the feasibility to prepare suspensions of cochleates or cochleate-like particles directly from a calcium salt of soy-PS by dialysis.

Sustainable preparation of spherical particles of novel carbamazepine-hesperetin cocrystal via different crystallization strategies: From mechanism to application

Spherical crystallization is widely employed in pharmaceutical industry to produce spherical particles that exhibit improved micrometric performances of active pharmaceutical ingredients (APIs), including particle size, morphology, flowability, and compressibility. Especially for APIs with poor powder performance and low solubility, spherical co-crystallization offers the potential to enhance both dissolution properties and tablet manufacturability by combining the API and cocrystal coformer (CCF) into a spherical particle. In this study, we aimed to enhance the physicochemical properties of carbamazepine (CBZ) and hesperetin (HPE) by synthesizing a novel cocrystal with the stoichiometric ratio of 1:1. Crystal structure of the CBZ-HPE cocrystal was determined using single crystal X-ray diffraction (SCXRD). To further improve the poor powder performances such as low flowability and compressibility resulting from the needle morphology of the cocrystals, we designed three spherical crystallization strategies: common spherical agglomeration, oil-out-induced spherical agglomeration and spherulitic growth method. The spherical particles of CBZ-HPE cocrystals were characterized by powder X-ray diffraction (PXRD), polarized light microscopy (PLM), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), particle size instrumentation, and Fourier transform infrared spectroscopy (FTIR) to provide information about crystal structure, particle morphology, particle size and circularity distribution. The results revealed significant differences in particle morphology, flowability, particle size and dissolution rate among the various spherical crystallization strategies. Theoretical calculations elucidated three spherical crystallization mechanisms: spherical agglomeration (SA), oil-out-induced spherical agglomeration (OOSA) and spherulite growth (SG). This study offers both experimental and theoretical foundations for the application of different spherical crystallization techniques in the pharmaceutical industry.

Rapid preparation of starch nanocrystals by the mixed acid of sulfuric acid and hydrochloric acid

In this work, waxy maize starch nanocrystals were prepared by mixed acid of sulfuric acid and hydrochloric acid for the first time. Physicochemical properties, crystalline structure, and particle size of starch nanocrystals prepared by mixed acid (HSNC) were measured. The results showed that there was no difference in particle morphology, group structure, and surface elements of HSNC and starch nanocrystals prepared by sulfuric acid (SNC), which was a conventional preparation method. The yield of HSNC was lower than that of SNC. However, the preparation time of HSNC was greatly shortened to 1 h which is only 0.83 % of the time (5 d) to prepare SNC by the sulfuric acid, and HSNC showed higher relative crystallinity and smaller size than those of SNC. In addition, when the ratio of sulfuric acid and hydrochloric acid to provide H ion concentration was 1:1 to hydrolyze starch for >1 h, the crystal pattern of HSNC would be changed to V-typed, while the crystal pattern of SNC was still A-typed. Thus, this work provided efficient method for preparing starch nanocrystals is provided, which can replace sulfuric acid hydrolysis to prepare SNC.

Classification of scanning electron microscope images of pharmaceutical excipients using deep convolutional neural networks with transfer learning

Convolutional Neural Networks (CNNs) are image analysis techniques that have been applied to image classification in various fields. In this study, we applied a CNN to classify scanning electron microscopy (SEM) images of pharmaceutical raw material powders to determine if a CNN can evaluate particle morphology. We tested 10 pharmaceutical excipients with widely different particle morphologies. SEM images for each excipient were acquired and divided into training, validation, and test sets. Classification models were constructed by applying transfer learning to pretrained CNN models such as VGG16 and ResNet50. The results of a 5-fold cross-validation showed that the classification accuracy of the CNN model was sufficiently high using either pretrained model and that the type of excipient could be classified with high accuracy. The results suggest that the CNN model can detect differences in particle morphology, such as particle size, shape, and surface condition. By applying Grad-CAM to the constructed CNN model, we succeeded in finding particularly important regions in the particle image of the excipients. CNNs have been found to have the potential to be applied to the identification and characterization of raw material powders for pharmaceutical development.

Provenance fingerprints of atmospheric dust collected at Granada city (Southern Iberian Peninsula). Evidence from quartz grains

Dust in the Earth́s atmosphere is increasing, particularly in southern Spain. The study of dust properties allows for a hypothesis on the origin and provenance of dust. This study characterised atmospheric dust deposited in the city of Granada (south of Spain) during three spring periods (samples 4PA, 16PA, and 28PA, collected in 2012, 2013, and 2014, respectively). The aim was to ascertain dust characteristics and genesis using a set of methodological techniques. The backward trajectories study separated the samples into two groups: scarce Saharan influence (sample 16PA, 6% of backward trajectories are from, or have passed through, Africa) and greater influence (samples 4PA and 28PA, 26% and 33%, respectively). This grouping was verified by the rest of the properties analysed, namely, PM10 concentration, deposition rates, grain size, mineralogy, and elemental composition (minor, including rare earth elements). In addition, mineral quartz showed differences in particle morphology and surface microtextures. The mineralogical and geochemical studies of our samples have proved similarities with other dust collected in Granada and soils from the Iberian Peninsula. The principal component analysis of the quartz shape parameters insists on the differentiation of these groups. We propose the morphoscopy of quartz grains (a significant component of atmospheric dust) as a fingerprint of provenance.

Study on the particle morphology, powder characteristics and hydration activity of blast furnace slag prepared by different grinding methods

This paper compares and studies the particle morphology, particle size distribution (PSD) characteristics, powder characteristics and hydration characteristics of ground granulated blast furnace slag prepared by a ball mill and a vertical roller mill. Both types of slag particles are found to comply with the Rosin–Rammler–Bennett (RRB) distribution model. The degree of sphericity of the blast furnace slag powder particles decreases with the particle size and is lower when produced by vertical roller milling than by ball milling; the differences in particle morphology mainly exist at the 0–3 μm particle grade. For the same specific surface area, ball-milled slag powder has a higher angle of repose, natural bulk density and tapped bulk density than does vertical-roller-milled slag powder. Both slag powders are categorized as Coulomb solids, which exhibit cohesiveness and high flow resistance. Ball-milled slag powder has better hydration activity than that of vertical-roller-milled slag powder. The difference in the homogeneity coefficients of the two powders is important to the obvious differences in the particle characteristics and hydration activities of the ball-milled and vertical-roller-milled slags.

Imaging of the Effect of Alcohol-Containing Media on the Performance of Hypromellose Hydrophilic Matrix Tablets: Comparison of Direct Compression and Regular Grades of Polymer.

As the ingestion of drug products with alcohol could have adverse effects on the release of drugs from dosage forms, it is important to understand the mechanisms underpinning the influence on drug release by evaluating the effect of alcohol-containing media on the behaviour of pharmaceutical excipients. In this work, the effect of hydroalcoholic media containing up to 40% v/v absolute ethanol was evaluated, employing both the regular (CR) and direct compression grades (DC) of hypromellose. X-ray microtomography (XµT) and magnetic resonance imaging (MRI) were used as complementary techniques in determining the influence of the media composition on the ability of the CR and DC polymers to form and evolve the gel layer that controls drug release. Particle and powder properties of the polymer were characterised to determine any relationship to performance in hydroalcoholic media. Triboelectrification results showed the CR grade formulation to charge electropositively whereas the DC grade charged electronegatively. The flow properties also showed the DC grade to have a superior flow as compared to its CR counterpart. Differences in particle morphology between the grades influenced charging and flow behaviour of the powders; however, it did not seem to impact significantly either on the mechanical strength or the drug release properties of the compacted formulation using the model drug propranolol HCl. XµT and MRI imaging were successfully used as complementary techniques in determining the gel layer/hydration layer thickness measurements as the layer developed, as well as following ingress of hydroalcoholic media and its impact on the dry core. The result showed that although differences were present in the gel layer thickness potentially due to differences in particle morphology, this also did not impact significantly on the dissolution process, especially in acidic and hydroalcoholic media.

The properties of FeOOH precipitates formed in CTAB-rich FeCl3 solutions at various pH and ethanol contents

Iron oxyhydroxides as an important adsorbent, catalyzer, or electrode material can be commonly prepared in surfactant-rich ferric solutions. Herein in this work, we investigated influences of pH and the ethanol/water volume ratio on iron precipitates produced in FeCl3 solutions with cetyltrimethyl ammonium bromide (CTAB) at 40 °C. The resulting iron oxyhydroxides were characterized and their properties were also analyzed. Results consistently indicated that mineral phases and crystallinities of the products in CTAB-rich FeCl3 solutions were mainly influenced by pH, and the unstable phase of ferrihydrite was favorable to transform to goethite as the pH values increased. Ethanol addition could have a negative impact on phases and crystallinities of the formed iron oxyhydroxides and also inhibit aggregation of the product particles resulting from CTAB action. Differences in particle morphologies and sizes could be mainly attributed to phases and crystallinities of the formed FeOOH, as well as presence of CTAB and ethanol.

Use of digital image analysis combined with fractal theory to determine particle morphology and surface texture of quartz sands

The particle morphology and surface texture play a major role in influencing mechanical and hydraulic behaviors of sandy soils. This paper presents the use of digital image analysis combined with fractal theory as a tool to quantify the particle morphology and surface texture of two types of quartz sands widely used in the region of Vitória, Espírito Santo, southeast of Brazil. The two investigated sands are sampled from different locations. The purpose of this paper is to present a simple, straightforward, reliable and reproducible methodology that can identify representative sandy soil texture parameters. The test results of the soil samples of the two sands separated by sieving into six size fractions are presented and discussed. The main advantages of the adopted methodology are its simplicity, reliability of the results, and relatively low cost. The results show that sands from the coastal spit (BS) have a greater degree of roundness and a smoother surface texture than river sands (RS). The values obtained in the test are statistically analyzed, and again it is confirmed that the BS sand has a slightly greater degree of sphericity than that of the RS sand. Moreover, the RS sand with rough surface texture has larger specific surface area values than the similar BS sand, which agree with the obtained roughness fractal dimensions. The consistent experimental results demonstrate that image analysis combined with fractal theory is an accurate and efficient method to quantify the differences in particle morphology and surface texture of quartz sands.

Effects of the Preparation Process on the Properties of Amorphous Solid Dispersions.

The use of amorphous solid dispersions to improve the bioavailability of active ingredients from the BCS II and IV classifications continues to gain interest in the pharmaceutical industry. Over the last decade, methods for generating amorphous solid dispersions have been well established in commercially available products and in the literature. However, the amorphous solid dispersions manufactured by different technologies differ in many aspects, primarily chemical stability, physical stability, and performance, both in vitro and in vivo. This review analyzes the impact of manufacturing methods on those properties of amorphous solid dispersions. For example, the chemical stability of drugs and polymers can be influenced by differences in the level of thermal exposure during fusion-based and solvent-based processes. The physical stability of amorphous content varies according to the thermal history, particle morphology, and nucleation process of amorphous solid dispersions produced by different methods. The in vitro and in vivo performance of amorphous formulations are also affected by differences in particle morphology and in the molecular interactions caused by the manufacturing method. Additionally, we describe the mechanism of manufacturing methods and the thermodynamic theories that relate to amorphous formulations.

Secondary Organic Aerosol (SOA) from Nitrate Radical Oxidation of Monoterpenes: Effects of Temperature, Dilution, and Humidity on Aerosol Formation, Mixing, and Evaporation.

Nitrate radical (NO3) oxidation of biogenic volatile organic compounds (BVOC) is important for nighttime secondary organic aerosol (SOA) formation. SOA produced at night may evaporate the following morning due to increasing temperatures or dilution of semivolatile compounds. We isothermally dilute the oxidation products from the limonene+NO3 reaction at 25 °C and observe negligible evaporation of organic aerosol via dilution. The SOA yields from limonene+NO3 are approximately constant (∼174%) at 25 °C and range from 81 to 148% at 40 °C. Based on the difference in yields between the two temperatures, we calculated an effective enthalpy of vaporization of 117-237 kJ mol-1. The aerosol yields at 40 °C can be as much as 50% lower compared to 25 °C. However, when aerosol formed at 25 °C is heated to 40 °C, only about 20% of the aerosol evaporates, which could indicate a resistance to aerosol evaporation. To better understand this, we probe the possibility that SOA from limonene+NO3 and β-pinene+NO3 reactions is highly viscous. We demonstrate that particle morphology and evaporation is dependent on whether SOA from limonene is formed before or during the formation of SOA from β-pinene. This difference in particle morphology is present even at high relative humidity (∼70%).

Laser ablation of titanium in liquid in external electric field

Ablation of a bulk Ti target by 10ps laser pulses in water is experimentally studied in external DC electric field. It is demonstrated that both lateral size of nanostructures (NS) on Ti surface and their density depend on the electric field applied to the target. Scanning Electron Microscopy of NS reveals the shift of their size distribution function toward larger sizes with applied field (cathodic bias, 25V DC). Density of mushroom-like NS with applied electric field amounts to 1010cm−2. X-ray diffraction of generated nanoparticles (NPs) shows difference in the crystallographic structure of NPs of non-stoichiometric Ti oxides generated with and without electric field. This conclusion is corroborated with the optical absorption spectroscopy of obtained colloids. Transmission Electron Microscopy of NPs also shows difference in morphology of particles produced with and without cathodic bias. The results are interpreted on the basis of instability of the melt on Ti surface in the electric field.

Increasing synthesis yield of K‐doped tungsten oxide nanowire using stirred hydrothermal reactor and its near‐infrared reflectance property

One-dimensional nanostructured oxides are typically synthesised by the hydrothermal method in a small pressurised reactor under static conditions that usually results in a low synthesis yield. In this reported work, K-doped tungsten oxide (K2W4O13) nanowires were synthesised under stirred hydrothermal treatment of hydrous K2W4O13 precursor in the presence of K2SO4 employed as the shape-directing agent to promote the formation of nanowires. Under static conditions (0 rpm), only 24.6% yield was obtained. The yield was significantly increased with the increase of stirring speed. The yield of 90.3%, almost four times the static condition, was obtained when synthesised under continuous stirring at 500 rpm. The samples synthesised from both the conditions have the same crystal structure, which is K2W4O13. However, the difference in particle morphology was observed; the average diameter of 11.4 ± 0.3 nm and the length up to several hundred micrometres were obtained from the stirred condition, while more irregularities of the nanowires (average diameter of 7.1 ± 1.1 nm and very diverse length) were obtained under static conditions. The more uniformity observed under stirred hydrothermal conditions is attributed to the more uniform crystallisation process attained under the stirring condition. A high near-infrared (NIR) reflectance of 91.3% suggests its NIR shielding ability.

Effect of morphology on light scattering by agglomerates

Using the discrete dipole approximation (DDA), we compute light scattering from irregularly shaped particles with three different types of agglomerate morphologies. The packing density of materials in the model particles spans the range from 0.169 through 0.336. We investigate four different refractive indices m=1.313+0i, 1.6+0.0005i, 1.5+0.1i, and 1.855+0.45i, which are representative of various cosmic and terrestrial materials in the visible. In each case, we consider a wide range of size parameters that makes it possible to average the light-scattering response over particle size with a power-law size distribution. We find that despite noticeable differences in particle morphology, their light-scattering responses are remarkably similar; the difference in light scattering often does not exceed the error bars occurring in laboratory measurements of micron-sized particles. On the contrary, the impact of refractive index and size distribution on light scattering appears to be much stronger compared with the morphology of complex, agglomerate particles. This finding may simplify considerably the interpretation of photo-polarimetric observations of atmospheric aerosols, cosmic dust particles, etc., because the precise specification of target-particle shape is unnecessary for the analysis.

Effect of Polyplex Morphology on Cellular Uptake, Intracellular Trafficking, and Transgene Expression

Nanoparticle morphology has been shown to affect cellular uptake, but there are few studies investigating the impact of particle shape on biologic drug delivery. Recently, our group synthesized a series of N-(2-hydroxypropyl) methacrylamide (HPMA)-oligolysine brush polymers for nucleic acid delivery that varied in oligolysine peptide length and polymer molecular weight. Interestingly, a 50% longer peptide (K15) transfected very poorly compared to the optimized polymer comprised of K10 peptide despite similar chemical composition and molecular weight. We hypothesized that differences in particle morphology contributed to the differences in plasmid DNA delivery. We found that particles formed with plasmid DNA and a polymer with the longer oligolysine peptide (pHK15) had larger aspect ratios than particles formed with optimized polymer (pHK10). Even though both formulations showed similar percentages of cellular association, particles of a higher aspect ratio were internalized to a lesser extent. Furthermore, the rod-like particles accumulated more in endosomal/lysosomal compartments, leading to delayed nuclear delivery. Other parameters, such as particle surface charge, unpackaging ability, uptake mechanism, intracellular trafficking, and the presence of heparan sulfate proteoglycans did not significantly differ between the two polymer formulations. These results indicate that, for this system, polyplex morphology primarily impacts nucleic acid delivery efficiency through differences in cellular internalization rates.

Influence of talc morphology on the mechanical properties of talc filled polypropylene

Injected polypropylene (PP)/talc composites were studied to evaluate the influence of different talc morphologies on their final mechanical properties. Talc genesis is responsible for type and content of associated minerals, crystalline degree, particle size distribution, and specially, morphology. Consequently, when talc is incorporated into PP, differences in the genesis mean differences in particle morphology and may influence the composite properties. Two talc samples having predominant macro and microcrystalline morphologies were used to prepare two composite sets to be tested. Thermal and mechanical properties of each PP/talc composites set were measured, analyzed and discussed comparatively. The results reveal that the main influences of talc morphology are given on modulus, yield strength and elongation at break of PP/talc composites. Macrocrystalline morphology of talc induces better composite mechanical properties than microcrystalline one. This behavior could be explained by talc characteristics as lamellarity, crystalline character and crystallinity degree.

Comparative Studies on Chitosan and Polylactic-co-glycolic Acid Incorporated Nanoparticles of Low Molecular Weight Heparin

This study was performed to test the feasibility of chitosan and polylactic-co-glycolic acid (PLGA) incorporated nanoparticles as sustained-release carriers for the delivery of negatively charged low molecular weight heparin (LMWH). Fourier transform infrared (FTIR) spectrometry was used to evaluate the interactions between chitosan and LMWH. The shifts, intensity, and broadening of the characteristic peaks for the functional groups in the FTIR spectra indicated that strong interactions occur between the positively charged chitosans and the negatively charged LMWHs. Three types of LMWH nanoparticles (NP-1, NP-2, and NP-3) were prepared using chitosan with or without PLGA: NP-1 nanoparticles were formed by polyelectrolyte complexation after single mixing, NP-2 nanoparticles were prepared by polyelectrolyte complexation after single emulsion-diffusion-evaporation, and NP-3 nanoparticles were optimized by double emulsion-diffusion-evaporation. NP-3 nanoparticles of LMWH prepared by the emulsion-diffusion-evaporation method showed significant differences in particle morphology, size, zeta potential, and drug release profile compared to NP-1 nanoparticles formed by polyelectrolyte complexation. Another ionic complex of LMWH with chitosan-incorporated PLGA nanoparticles (NP-2) showed lower drug entrapment efficiency than that of NP-1 and NP-3. The drug release rate of NP-3 was slower than the release rates of NP-1 and NP-2, although particle morphology of NP-3 was similar to that of NP-2. Cell viability was not adversely affected when cells were treated with all three types of nanoparticles. The data presented in this study demonstrate that nanoparticles formulated with chitosan-PLGA could be a safe sustained-release carrier for the delivery of LMWH.