Typical Formulation Research Articles

A Revision of Polymeric Nanoparticles as a Strategy to Improve the Biological Activity of Melatonin.

Drug delivery systems based on nanotechnology exhibit a number of advantages over traditional pharmacological formulations. Polymeric nanoparticles are commonly used as delivery systems and consist of synthetic or natural polymers that protect drugs from degradation in physiological environments. In this context, indolamine melatonin has been associated with several biological functions, including antioxidant, antitumor, immunoregulatory, neuroprotective, and cardioprotective effects. However, its availability, half-life, and absorption depend upon the route of administration, and this can limit its therapeutic potential. An alternative is the use of polymeric nanoparticle formulations associated with melatonin to increase its bioavailability and therapeutic dose at sites of interest. Thus, the objective of this review is to provide a general and concise approach to the therapeutic association between melatonin and polymeric nanoparticles applied to different biological disorders and to also highlight its advantages and potential applications compared to those of the typical drug formulations that are available.

Precise Regulation of Combustion Characteristics of High-Energy Composite Propellants by Incorporation of CL-20 Crystals Intercalated with Energetic Burn Rate Modifiers.

In this study, a 2D structured triaminoguanidine-glyoxal polymer with a high nitrogen content has been coordinated with metal ions to produce energetic metal complexes (TAGP-Ms) employed as energetic burn rate inhibitors. The metal ions (Ba2+, K+, and Ca2+) are elaborately selected based on their ability of suppressing the burn rate of composite propellants. The CL-20 crystals were intercalated with prepared TAGP-Ms materials via a solvent-antisolvent method for realization of the precise control on burning behaviors of studied propellants. The influence of TAGP-Ms inhibitors on thermal decomposition and combustion characteristics of high-energy composite propellants was evaluated using thermal analysis and a combustion diagnostic method. Results of TGA/DSC-FTIR measurements suggest that the thermal decomposition of CL-20-containing composite propellants was found to be constrained by varied degrees as a result of TAGP-Ms additions, in which the TAGP-K displays a stronger effect on suppressing the thermal decomposition of CL-20 compared with that of other TAGP-Ms. The FTIR spectra indicate that the primary gaseous phase products are composed of N2O, H2O, and CO2 in CL-20 decomposition, as well as by HCl, H2O, NO2, and N2O in the decomposition of AP for all studied composite propellants. The combustion characterizations show that the TAGP-K-containing composite propellant exhibits a significantly reduced rate of heat release but is associated with a higher flame radiation intensity increased by 4.2% compared with that of the reference propellant, which clearly implies that the TAGP-K is capable of suppressing the energy release rate while ensuring the high energetic features of propellants to be well maintained. Moreover, the burn rate pressure exponents are considerably decreased by ∼10% for the TAGP-K-containing propellants in comparison with those of propellants with the typical formulation, which strongly suggests that TGAP-Ms are promising candidates for tuning the combustion behaviors of composite propellants by influencing the decomposition processes of CL-20 and AP collectively.

Emergence of a Bose polaron in a small ring threaded by the Aharonov-Bohm flux

The model of a ring threaded by the Aharonov-Bohm flux underlies our understanding of a coupling between gauge potentials and matter. The typical formulation of the model is based upon a single particle picture, and should be extended when interactions with other particles become relevant. Here, we illustrate such an extension for a particle in an Aharonov-Bohm ring subject to interactions with a weakly interacting Bose gas. We show that the ground state of the system can be described using the Bose-polaron concept—a particle dressed by interactions with a bosonic environment. We connect the energy spectrum to the effective mass of the polaron, and demonstrate how to change currents in the system by tuning boson-particle interactions. Our results suggest the Aharonov-Bohm ring as a platform for studying coherence and few- to many-body crossover of quasi-particles that arise from an impurity immersed in a medium.

Study on development and tissue permeation of different formulations of Fasudil.

The study is intended to formulate Fasudil loaded vesicular system for application in the management of angina. Fasudil was made into a complex with phospholipid, and other different formulations were made, including Fasudil solution, liposomal form, and Fasudil loaded into the gel. A drug characterization study was conducted and noted. Drug release was quantified and analyzed and, finally, inoculated in Sprague-Dawley rats. These rats underwent anginal induction, and each formulation's effect on angina was evaluated. Drug solution (F-Phos) and F-Phos-Lipo (liposomal dispersion form of the drug) have shown that more than half percent of them have been released within 1.5 hours, and the rapid release occurred from liposomal dispersion in the first hour. The study determined the viscosity of the different formulations, which was significantly (p<0.05) higher than the theoretical sum of the viscosity of each formulation. The study found that the F-Phos-Lipo+P-407HMS formulation is the most effective as its application has the minimum infarct area percentage compared to the other formulations and can also reduce creatine kinase levels significantly as compared to the different formulations (p<0.05). The study concluded that the typical gel formulation (liposomal Fasudil dispersed in hydroxypropyl methylcellulose solution, which is added to blank poloxamer 407) had been shown to have significantly anti-anginal properties, including easy administration, its application on the infarct area percentage and subsequently its pharmacological effect on the cardiac tissue.

Covering All the Bases: Type-Based Verification of Test Input Generators

Test input generators are an important part of property-based testing (PBT) frameworks. Because PBT is intended to test deep semantic and structural properties of a program, the outputs produced by these generators can be complex data structures, constrained to satisfy properties the developer believes is most relevant to testing the function of interest. An important feature expected of these generators is that they be capable of producing all acceptable elements that satisfy the function’s input type and generator-provided constraints. However, it is not readily apparent how we might validate whether a particular generator’s output satisfies this coverage requirement. Typically, developers must rely on manual inspection and post-mortem analysis of test runs to determine if the generator is providing sufficient coverage; these approaches are error-prone and difficult to scale as generators become more complex. To address this important concern, we present a new refinement type-based verification procedure for validating the coverage provided by input test generators, based on a novel interpretation of types that embeds “ must -style” underapproximate reasoning principles as a fundamental part of the type system. The types associated with expressions now capture the set of values guaranteed to be produced by the expression, rather than the typical formulation that uses types to represent the set of values an expression may produce. Beyond formalizing the notion of coverage types in the context of a rich core language with higher-order procedures and inductive datatypes, we also present a detailed evaluation study to justify the utility of our ideas.

Influence of the Protein-Based Emulsions on the Rheological, Thermo-Mechanical and Baking Performance of Muffin Formulations

The impact of replacing the sunflower oil in a typical muffin formulation with different protein-based emulsions was investigated. Fundamental rheological measurements indicated significant differences between emulsions prepared with soy, lupin, and yeast proteins. The highest viscosity of 2.04 Pa·s was registered for the lupin protein-based emulsion, whereas the yeast protein-based emulsion exhibited the narrowest linear viscoelastic region. The influence of the protein-based emulsions on the thermo-mechanical properties of wheat flour dough was further investigated using the Mixolab device and Chopin+ protocol. Oil substitution with emulsion resulted in better starch gelatinization with the C3 torque of 0.46 Nm being registered for doughs with soy and lupin protein emulsions. Significant differences in terms of moisture, color, porosity, and texture were observed between muffins prepared with protein-based emulsions and control. The lower fat baked products retained higher amounts of water (25.05–26.00%) and exhibited slightly more vivid color (color intensity of 46.34–46.81) and harder texture (firmness of 5.64–5.86 N). The sensory analysis confirmed that soy, lupin, and yeast protein emulsions can be used for obtaining muffin samples with acceptable taste and flavor, and overall quality comparable to the control. These results indicate that the protein based-emulsions are promising oil replacers in muffin formulations.

A Systematic Survey of General Sparse Matrix-matrix Multiplication

General Sparse Matrix-Matrix Multiplication (SpGEMM) has attracted much attention from researchers in graph analyzing, scientific computing, and deep learning. Many optimization techniques have been developed for different applications and computing architectures over the past decades. The objective of this article is to provide a structured and comprehensive overview of the researches on SpGEMM. Existing researches have been grouped into different categories based on target architectures and design choices. Covered topics include typical applications, compression formats, general formulations, key problems and techniques, architecture-oriented optimizations, and programming models. The rationales of different algorithms are analyzed and summarized. This survey sufficiently reveals the latest progress of SpGEMM research to 2021. Moreover, a thorough performance comparison of existing implementations is presented. Based on our findings, we highlight future research directions, which encourage better design and implementations in later studies.

Catanionic Vesicles as a Facile Scaffold to Display Natural N-Glycan Ligands for Probing Multivalent Carbohydrate-Lectin Interactions.

Multivalent interactions are a key characteristic of protein-carbohydrate recognition. Phospholipid-based liposomes have been explored as a popular platform for multivalent presentation of glycans, but this platform has been plagued by the instability of typical liposomal formulations in biological media. We report here the exploitation of catanionic vesicles as a stable lipid-based nanoparticle scaffold for displaying large natural N-glycans as multivalent ligands. Hydrophobic insertion of lipidated N-glycans into the catanionic vesicle bilayer was optimized to allow for high-density display of structurally diverse N-glycans on the outer membrane leaflet. In an enzyme-linked competitive lectin-binding assay, the N-glycan-coated vesicles demonstrated a clear clustering glycoside effect, with significantly enhanced affinity for the corresponding lectins including Sambucus nigra agglutinin (SNA), concanavalin A (ConA), and human galectin-3, in comparison with their respective natural N-glycan ligands. Our results showed that relatively low density of high-mannose and sialylated complex type N-glycans gave the maximal clustering effect for binding to ConA and SNA, respectively, while relatively high-density display of the asialylated complex type N-glycan provided maximal clustering effects for binding to human galectin 3. Moreover, we also observed a macromolecular crowding effect on the binding of ConA to high-mannose N-glycans when catanionic vesicles bearing mixed high-mannose and complex-type N-glycans were used. The N-glycan-coated catanionic vesicles are stable and easy to formulate with varied density of ligands, which could serve as a feasible vehicle for drug delivery and as potent inhibitors for intervening protein-carbohydrate interactions implicated in disease.

Order calibrated functional beamforming for constant mainlobe width

This paper introduces a beamformer with constant mainlobe width over a given frequency range based on the well-known Functional Beamforming. In fact, one of the main issues with Conventional and Functional Beamforming is the worsening of spatial resolution towards lower frequencies. The idea presented here is to exploit the order (exponent in its typical formulation) of Functional Beamforming as a leverage to maintain the same mainlobe width for different analysis frequencies. A strategy for accurately measure the mainlobe size is described and exploited for characterizing any array used in the beamforming analysis. An order calibration procedure, which boils down to the estimation of two fitting coefficients describing the proper beamformer order, is proposed. The procedure resulted useful to achieve a constant mainlobe size across a given frequency range. The validity of the whole approach is demonstrated on both synthesized and experimental data.

Development of Topical Nanogel as a Promising Delivery of NSAID’s Tenoxicam using Natural Permeation Enhancer Essential Oil (Euckolyptus)

Tenoxicam (TNX) is an effective non-steroidal anti-inflammatory drug (NSAIDs) used to treat rheumatoid arthritis. Like other NSAIDs, tenoxicam has the disadvantage of being linked to gastrointestinal side effects. Furthermore, this drug is having weak transdermal penetration, preventing transdermal administration. The goal of this study was to develop a TNX nanogel with a smaller particle size to improve the anti-inflammatory drug's bioavailability and assess its potential in rheumatoid arthritis. The modified emulsification-diffusion method is used to develop nanosized dispersion of TNX using noveon polycarbophil AA-1 as a gelling agent. Moreover, essential oils increase skin penetration by interacting with the stratum corneum (SC). They were found to be successful in increasing skin penetration of both lipophilic and hydrophilic drugs. The rheology, particle size, drug content, % drug release, and in-vitro diffusion study of prepared TNX nanogel were performed. Based on the rheological features of the formulations it was found to be substantial, with the particle size of 125.05nm and zeta potential -8.47mV, drug content of 97.05%, % drug release 97.40% drug diffusion of 97.42%, and pH of 6.2. Tenoxicam nanogel was prepared by using noveon polycarbophil AA-1 and eucalyptus oil as a permeation enhancer was proven to be suitable as a typical topical gel formulation for the treatment of edema and rheumatoid arthritis.

Cytotoxicity Mechanisms of Eight Major Herbicide Active Ingredients in Comparison to Their Commercial Formulations.

Commercial pesticide formulations contain co-formulants, which are generally considered as having no toxic effects in mammals. This study aims to compare the toxicity of 8 major herbicide active ingredients-namely glyphosate, dicamba, 2,4-D, fluroxypyr, quizalofop-p-ethyl, pendimethalin, propyzamide and metazachlor-with a typical commercial formulation of each active ingredient. Cytotoxicity and oxidative stress capability was assessed in human hepatoma HepG2 cells. Using an MTT assay, formulations of glyphosate (Roundup Probio), fluroxypyr (Hurler), quizalofop-p-ethyl (Targa Super) and dicamba (Hunter) were more toxic than the active ingredient alone. Metazachlor and its formulation Sultan had similar cytotoxicity profiles. Cytotoxicity profiles were comparable in immortalised human fibroblasts. Toxilight necrosis assays showed the formulation of metazachlor (Sultan50C) resulted in significant membrane disruption compared to the active ingredient. Generation of reactive oxygen species was detected for glyphosate, fluroxypyr, pendimethalin, quizalofop-p-ethyl, the formulation of 2,4-D (Anti-Liserons), and dicamba and its formulation Hunter. Further testing of quizalofop-p-ethyl and its formulation Targa Super in the ToxTracker assay system revealed that both products induced oxidative stress and an unfolded protein response. In conclusion, these results show that most herbicide formulations tested in this study are more toxic than their active ingredients in human tissue culture cell model systems. The results add to a growing body of evidence, which implies that commercial herbicide formulations and not just their active ingredients should be evaluated in regulatory risk assessment of pesticides.

Heteroaggregation effects on Pickering stabilization using oppositely charged cellulose nanocrystal and nanochitin

Pickering emulsions are stabilized using complexes of cellulose nanocrystals (CNC) and nanochitin (NCh). The colloidal behavior and heteroaggregation in aqueous media are studied in relation to complex formation and net charge. The complexes are remarkably effective in stabilizing oil-in-water Pickering emulsions under conditions of slightly net positive or negative charges, as determined by the CNC/NCh mass ratio. Close to charge neutrality (CNC/NCh ~5), large heteroaggregates form, resulting in unstable emulsions. By contrast, under net cationic conditions, interfacial arrest of the complexes leads to non-deformable emulsion droplets with high stability (no creaming for 9 months). At given CNC/NCh concentrations, emulsions with up to 50% oil fraction are produced. This study shows how to control emulsion properties beyond consideration of the typical formulation variables, for instance, through adjusting CNC/NCh ratio or charge stoichiometry. We highlight the possibilities that are available for emulsion stabilization by using a combination of polysaccharide nanoparticles.

Three-dimensional failure envelope of concrete dam shear keys

Shear keys provide interlocking mechanisms along the vertical contraction joints of many concrete gravity dams. The shear key ultimate shear capacity is typically estimated as a function of the friction and cohesion that could be mobilised across a 2D shear plane located at the base of the key when subjected to a normal confinement pressure, P. A two-dimensional response of dam monoliths and shear keys shearing-off at their bases, is assumed. However, evidence of 3D interlocking behaviour between dam monoliths and the possibility of different key failure mechanisms involving interacting axial, P, shear, V, moment, M, and torsion, T, indicates that typical empirical formulations could significantly overestimate the actual shear key capacity under floods and seismic loadings. This paper presents an evaluation of the load–displacement response of shear keys subjected to multiaxial loading via nonlinear finite element analyses. A concrete “Continuous Surface Cap Model” (CSCM), available in the computer program LS-Dyna, is first shown to best capture the experimental shear keys' ultimate and residual shear capacity responses among five constitutive models. The effects of the tensile strength, fracture energy, confinement pressure, friction coefficient, initial opening, and dilation conditions on the load–displacement response of keys are investigated. Failure envelopes considering the key multiaxial shear capacity with confinement pressure, P, moment, M, and torsion, T, are developed. The ratios between moment and shear, M/V, and torsion and shear, T/V, control the failure mechanism. Increasing these ratios significantly reduce the ultimate shear capacity.

A new nitrate-based energetic molecular perovskite as a modern edition of black powder

In recent years, energetic molecular perovskites, which serve as an energetic material design platform, have shown potential for designing primary and secondary explosives. To explore their potential in gunpowder and pyrotechnics, this study constructed a new nitrate-bridged molecular perovskite, (H2dabco)[K(NO3)3] (DAN-2, H2dabco2+ ​= ​1,4-diazabicyclo-[2.2.2.]octane-1,4-diium), based on potassium nitrate—a major component of black powder. The single-crystal structure analysis indicated that DAN-2 possesses a cubic perovskite structure in the space group Pm3¯m. Theoretical calculations revealed that DAN-2 has an energy level slightly higher than TNT and much higher than black powder. Adding DAN-2 into a typical propellant formulation can increase the impetus while significantly lowering the flame temperature. Moreover, DAN-2 has a lower sensitivity (IS ​= ​29 ​J, FS > 360 ​N) than TNT (IS ​= ​15 ​J, FS ​= ​360 ​N). It is worth mentioning that DAN-2 can avoid the environmental concern of sulfide-induced acid rain since it does not bear any sulfur. Therefore, DAN-2 can be considered a new single explosive and a modern edition of black powder obtained via mixing oxidative KNO3 and a reductive organic fuel at the molecular scale. Furthermore, it displays promising potential in the field of gunpowder and pyrotechnics.

Performance Mapping toward Optimal Addition Levels and Processing Conditions for Different Types of Hydrocarbon Waxes Typically Used as External Lubricants in Sn-Stabilized PVC Pipe Formulations.

The mechanism of performance of hydrocarbon waxes used as external lubricants in typical PVC pipe formulations is not completely understood or defined. This study will benefit pipe manufacturers to tailor PVC processing conditions and wax addition levels to enhance the value of waxes with different molecular architectures in Sn-stabilized PVC formulations. A selection of waxes was comprehensively analyzed to understand how their structural and morphological differences impact the fusion behavior of a Sn-stabilized PVC compound. Results showed a high probability of fusion for waxes with melting points between 65 and 80 °C and a kinematic viscosity (at 135 °C) of less than 5 cSt across all experimental temperatures and concentration levels tested. The general probability of fusion increased with increasing temperature and decreasing wax concentration. Wax compositional differences only had a large impact on PVC fusion at lower experimental temperatures and high wax concentrations. The stable time and onset of degradation were found to be sensitive to experimental temperature but less so to wax concentration. High melting waxes had the lowest fusion torque but a narrow operating window in terms of concentration and temperature for a successful fusion to occur. Overall, fully refined paraffin waxes had the widest operating window and were less sensitive to a change in the wax concentration and experimental temperature than the rest of the waxes that were tested.

A Nitrite Excipient Database: A Useful Tool to Support N-Nitrosamine Risk Assessments for Drug Products

N-Nitrosamine risk assessment and control have become an integral part of pharmaceutical drug product development and quality evaluation. Initial reports of nitrosamine contamination were linked with the drug substance and its manufacturing process. Subsequently, the drug product and aspects of the formulation process have shown to be relevant. Regarding specific formulation contributions to nitrosamine content in a product, one risk lies in possible interactions between nitrosating agents, derived from nitrite in excipients, and vulnerable amines, either present as moieties of the active molecule or as impurities / degradants. However, the limited validated information on nitrite levels in excipients available until now, has been an obstacle for scientists to assess the risk of nitrosamine formation in pharmaceutical products. This has driven the creation of a database to store and share such validated information. The database, maintained by Lhasa Limited, constitutes a central platform to hold the data donated by the pharmaceutical company members on the nitrite concentrations in common excipients measured with validated analytical procedures. The goal of this data sharing initiative is to provide a common framework to contextualize and estimate the risk posed by presence of nitrites to contribute to the formation of nitrosamines in drug products. The major findings from the database analyses are: (1) average nitrite content and batch to batch variance differ among excipients, (2) for solid dosage forms, the nitrite contribution is dominated by the highest formula % excipients, e.g., the fillers (diluents), which are typically used in larger proportion, and are characterized by low nitrite levels and low variability, leading to an average value of 1 µg/g nitrite in a typical formulation, (3) substantial differences in average nitrite content in batches from different excipient vendors potentially reflecting differences in source materials or processing methods for excipient manufacturing. That final point suggests that future selection of raw materials or processing by excipient manufacturers may help reduce nitrite levels in finished drug product formulations, and thus the overall risk of nitrosamine formation in cases where the product contains vulnerable amines.

Formulation and Evaluation of Pravastatin Sodium Rapid Dissolving Films Using Various Hydrophilic Polymers

The current availability of a variety of novel oral administration technologies has enabled more effective pharmacokinetic and physicochemical investigations along with improved patient compliance. Typical solid-dosage formulations were replaced with rapid-dissolving films. An oral film dosage form that dissolves or disintegrates quickly in the mouth without the need for water is referred to as an "oral rapid dissolving film." The main objective of this study was to use the solvent casting method to explore rapid dissolving films of Pravastatin sodium using certain hydrophilic polymers, such as various grades of HPMC, PVA, and Ocimum basilicum mucilage powder. Various evaluation parameters were performed to the prepared films, including appearance, weight variation, thickness, folding endurance, moisture uptake, content homogeneity, and an in vitro disintegration and dissolution test. For stability testing, the optimized formulation was kept. The FTIR data revealed that there was no incompatibility between the medication and the polymers, and that all of the parameters were within the acceptable limits. FP9 (PVA 0.5%, OB 1.5 %) disintegrated the fastest of all the formulations, and the films remained stable. As a result, it may be stated that the Pravastatin sodium rapid dissolving films are possibly effective in treatment of hyperlipediemia with a rapid onset of action.

Recursive first fit: a highly parallel optimal solution to spectrum allocation

We revisit the classical spectrum allocation (SA) problem, a fundamental subproblem in optical network design, and make three contributions. First, we show how some SA problem instances may be decomposed into smaller instances that may be solved independently without loss of optimality. Second, we prove an optimality property of the well-known first-fit (FF) heuristic. Finally, we leverage this property to develop a recursive and parallel algorithm that applies the FF heuristic to find an optimal solution efficiently. This recursive FF algorithm is highly scalable because of two unique properties: (1) it completely sidesteps the symmetry inherent in SA and hence drastically reduces the solution space compared to typical integer linear programming formulations, and (2) the solution space can be naturally decomposed in non-overlapping subtrees that may be explored in parallel almost independently of each other, resulting in faster than linear speedup.

Environmental Effects on the Coefficient of Friction and Tack Adhesion of Formulated Waterborne Coatings

Waterborne coatings emit a low amount of harmful volatile organic compounds (VOCs) into the atmosphere compared to solvent-cast coatings. A typical waterborne formulation for agricultural applications consists of colloidal thermoplastic particles (latex) as the binder, a thickener to raise the viscosity, inorganic filler particles with a water-soluble dispersant, and a colloidal wax to modify surface properties. The formulations typically contain hygroscopic species that are potentially subject to softening by environmental moisture. The hardness, tack adhesion, and coefficient of friction of formulated coatings determines their suitability in applications. However, the relationship of these properties to the components in a coating formulation has not been adequately explored. Furthermore, the relationship between hygroscopic components and properties is an added complication. Here, we have characterized the hardness and tack adhesion of model formulated coatings using a single micro-indentation cycle with a conical indenter under controlled temperatures (above and below the glass transition temperature of a latex binder) and relative humidities. In parallel, we measured the coefficient of kinetic friction, μk, for the same coatings using a bespoke testing rig under controlled environmental conditions. Across a range of temperatures, RH and compositions, we find an inverse correlation between the coating hardness and μk. Any correlation of μk with the roughness of the coatings, which varies with the composition, is less clear. Formulations that contain wax additives have a higher μk at a low RH of 10%, in comparison to formulations without wax. For the wax formulations, μk decreases when the RH is raised, whereas in non-wax formulations, μk increases with increasing RH. Wax-containing coatings are hydrophilic (with a lower water contact angle), however the wax has a lower water permeability. A lubricating layer of water can explain the lower observed μk in these formulations. The addition of wax is also found to planarize the coating surface, which leads to higher tack adhesion in dry coatings in comparison to coatings without wax. Greater adhesive contact in these coatings can explain their higher friction. Our systematic research will aid the design of seed coating formulations to achieve their optimum properties under a wide range of environmental conditions.

A super-stable homogeneous Lipiodol-hydrophilic chemodrug formulation for treatment of hepatocellular carcinoma.

Background: Though lipiodol formulations are major options in transcatheter arterial chemoembolization (TACE) of advanced unresectable hepatocellular carcinoma (HCC) in the clinic, their application is severely limited by insufficient physical stability between the hydrophobic lipiodol and hydrophilic drugs; thus, most chemotherapeutic drugs are quickly released into systemic circulation resulting in poor therapeutic outcomes and serious side effects.Methods: The typical hydrophilic drug doxorubicin hydrochloride (DOX) was prepared as a pure nanomedicine and then stably and homogeneously dispersed in lipiodol (SHIFT&DOX) via slightly ultrasonic dispersion. The drug release profiles of SHIFT&DOX were defined in a decellularized liver model. In vivo therapeutic studies were performed in rat-bearing N1S1 orthotopic HCC models and rabbit-bearing VX2 orthotopic HCC models.Results: SHIFT&DOX features an ultrahigh homogeneous dispersibility over 21 days, which far surpassed typical Lipiodol-DOX formulations in clinical practice (less than 0.5 h). SHIFT&DOX also has excellent sustained drug release behavior to improve the local drug concentration dependence and increase the time dependence, leading to remarkable embolic and chemotherapeutic efficacy, and eminent safety in all of the orthotopic HCC models.Conclusions: The carrier-free hydrophilic drug nanoparticle technology-based lipiodol formulation provides a promising approach to solve the problem of drug dispersion in TACE with the potential for a translational pipeline.