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This work aimed to develop a nanosuspension (NSps) as an acetogenin (ACGs) carrier, using soy lecithin (SL) and hydroxypropyl-β-cyclodextrin (βCD) named NSps-βCDSL-ACGs. It was characterized by various spectroscopic techniques (DLS, FTIR, UV-vis diffuse reflectance). Moreover, the NSps morphology was observed by transmission electron microscopy (TEM). Also, the antibacterial activity of NSps-βCDSL-ACGs was evaluated against strains of interest in the poultry sector. NSps-βCDSL-ACGs presented nanometric size (207–239 nm), acceptable polydispersity index (PDI) values (0.13–0.17) and a high Z potential value (−47.17–50.36 mV), demonstrating high stability. The presence of ACGs in NSps-βCDSL-ACGs was confirmed by FTIR analysis. The nanoparticles had a spherical shape and exhibited high inhibition potential against Salmonella Enteritidis (88.18%), Streptococcus gallolyticus (88.01%), Salmonella Typhimurium (86.28%) and Salmonella Infantis (77.02%) strains up to 48 h, and a reduction of up to 3 log CFU/mL was achieved for S. Typhimurium. Therefore, NSps-βCDSL-ACGs is an attractive option for implementing ACGs administration in the poultry sector to reduce the use of antibiotics and minimize bacterial resistance. [ABSTRACT FROM AUTHOR]

The scarcity of existing and novel therapies for brain cancer has significantly affected the survival rate of glioblastoma patients. Mebendazole (MBZ), an antiparasitic agent demonstrated promising activity against brain cancer. However, poor solubility, multiple polymorphs, and insufficient permeability through blood–brain barrier (BBB) restricts its therapeutic efficacy through parenteral administration. The current study aimed to develop, optimize, and characterize sterile, injectable nanosuspension of mebendazole using parenterally acceptable stabilizers. Albumin and polysorbate 80 (PS-80) coated MBZ Nanosuspension (NS) was prepared using wet media milling technique. Design of experiment (DoE) approach was used to understand effect of drug loading versus stabilizer concentration. The optimized MBZ NS showed hydrodynamic diameter of 208.36 ± 0.24 nm with a poly dispersibility index (PDI) of 0.210 ± 0.03 and zeta potential of -20.41 ± 0.36 mV. The IC50 value of MBZ NS in U-87 MG and LN-229 cell lines were found to be 0.49 ± 0.02 μM and 0.48 ± 0.05 μM, respectively. Additionally, MBZ NS demonstrated a 2.65-fold decrease in colony-forming efficiency and a 1.16-fold reduction in migration of the bridging area compared to MBZ. In 3D spheroids of the U-87 MG glioma cell line, MBZ NS exhibited a 50% reduction in tumor growth and increased cell apoptosis compared to the control. MBZ NS formulations were sterilized by gamma irradiation and tested as per the USP sterility test. Albumin-PS 80 coated NS is rendered to be useful parenteral delivery of mebendazole for the treatment of brain cancer. [ABSTRACT FROM AUTHOR]

Pharmaceutical nanosuspensions, also called nanocrystals, are heterogeneous mainly aqueous dispersions of insoluble drug particles stabilised by surfactants and/or polymers. Nanosuspensions as liquid formulations suffer from instability. Solidification of nanosuspensions to solid dosage forms is a way to combine the advantages of nanocrystals with the advantages of the solid state. In this review, advances regarding stabilisation and production of nanosuspensions are briefly covered. Updates on the methods used to convert nanosuspensions to solid oral dosage forms (e.g., powder, granules, pellets, tablets, and films) are presented in depth. From these methods, spray drying and freeze drying are widely used. Granulation and hot-melt extrusion allow straightforward downstream processing, while printing exhibits the potential for dose personalisation. Focus is given on novel formulations (e.g., nano-cocrystals, nanocrystalline solid dispersions) which could further enhance the dissolution and bioavailability of poorly soluble drugs. [ABSTRACT FROM AUTHOR]

Objectives: Nanosuspensions are increasingly recognized as a valuable technology for enhancing poorly water-soluble drugs' solubility and dissolution rate, thereby improving their bioavailability. In this study, we employed ultrasonic-assisted precipitation to fabricate nanosuspensions of indomethacin (IND), utilizing Soluplus® (Sol) as a stabilizing agent. Our objectives were driven by hypotheses centered on optimizing formulation variables and developing predictive models for optimal IND formulations. Significance: This research highlights the Box-Behnken design (BBD) as a powerful tool that optimizes the properties of IND nanosuspensions, thus significantly enhancing their dissolution rate. Methods: The impacts of the independent variables on the mean particle size (MPS), polydispersity index (PDI), and zeta potential (ZP) were investigated using BBD. The optimized nanosuspension was freeze-dried with 3% trehalose to produce a dry nanosuspension (DNS). The DNS was characterized by SEM, DSC, XRPD, solubility, and dissolution. Results: The IND: Sol ratio and sonication power significantly affected the MPS and ZP of the nanosuspensions. The optimized formulation showed MPS, PDI, and ZP of 144.77 ± 6.68 nm, 0.26 ± 0.08, and −24.6 ± 1.90 mV, respectively. The DNS exhibited spherical particle morphology. The DSC and XRPD confirmed the amorphous state of IND with enhanced solubility and dissolution of IND. DNS showed a 3.7-fold increase in drug release in the first 15 min compared with raw IND. Conclusions: This study demonstrated the critical role of BBD in accurately predicting the values of independent variables essential for formulating optimal nanosuspensions. These formulations possess specific properties that can be effectively integrated into various dosage forms tailored for different routes of administration. [ABSTRACT FROM AUTHOR]

BACKGROUND: The presence of barnyardgrass poses a threat to global food security by reducing rice yields. Currently, herbicides are primarily applied for weed management. However, the effectiveness of herbicide deposition and uptake on barnyardgrass is limited as a consequence of the high wax content on leaves, low water solubility and extreme lipophilicity of herbicides. Therefore, it is imperative to develop novel formulations for efficient delivery of herbicides to improve herbicidal activity and reduce dosage. RESULTS: We successfully prepared nanosuspension(s) (NS) of quinclorac through the wet media milling technique. This NS demonstrates excellent physical stability and maintains nanoscale during dose transfer. The deposition concentration and uptake concentration of NS on barnyardgrass were 3.84–4.47‐ and 2.11–2.58‐fold greater than those traditional formulations, respectively. Moreover, the NS exhibited enhanced herbicidal activity against barnyardgrass at half the dosage required by conventional formulations without compromising rice safety. CONCLUSIONS: These findings suggest that NS can effectively facilitate the delivery of hydrophobic and poorly water‐soluble herbicide active ingredients, thereby enhancing their deposition, uptake and bioactivity. This study expands the potential application of NS in pesticide delivery, which can provide valuable support for optimizing pesticide utilization, improving economic efficiency and mitigating environmental risks. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Absorption is the most widely used carbon dioxide (CO2) removal technology. The CO2 absorption performance of monoethanolamine (MEA), the most commonly used CO2 absorbent, can be improved by suspending nanoparticles. This work examined the performance of graphene nanoplatelets (GNPs) as additives to enhance CO2 absorption in MEA. The GNPs were characterized by HRTEM, FTIR, and XRD. The study examined the influence of GNP concentrations on CO2 absorption at room temperature. The images from HRTEM confirmed that the implemented graphene consists of several layers of graphene sheets. Increasing the loading of particles increased the solubility of CO2 until the optimum concentration was reached. From this work, it is evident that incorporating GNPs into MEA enhances the CO2 absorption performance of MEA. Thus, the addition of nanoparticles to the absorbent can enhance its CO2 absorptivity. [ABSTRACT FROM AUTHOR]

Nanocrystals is an important pharmaceutics approach to improve the drug efficacy of insoluble candidate compounds. However, the current nanocrystal-targeted delivery strategy and delivery efficiency are still difficult to fulfill the standard of clinical treatment. To provide reference for the targeted delivery of nanocrystals, the nanocrystal-targeting methods and efficiency was systematically commented. Furthermore, the effect of particle size on the targeted delivery of nanocrystals and the effect of the combination of nanocrystals with conventional dosage forms on the targeted delivery were also summarized. This review is conducive to promoting the development of nanocrystal-targeted delivery formulation technology, and provides reference for the methods of nanocrystal-targeted delivery. [ABSTRACT FROM AUTHOR]

The aim in this study was to develop and evaluate a nanofluconazole (FLZ) formulation with increased solubility and permeation rate using nanosuspensions. The FLZ nanosuspensions were stabilized using a variety of stabilizing agents and surfactants in various concentrations. The FLZ nanosuspension was characterized in vitro using particle size, zeta potential, X-ray powder diffraction (XRPD), and solubility. In addition, the ex vivo ocular permeation of FLZ through a goat cornea was analyzed. The results showed that the particle size of all nanosuspension formulations was in the nanometer range from 174.5 ± 1.9 to 720.2 ± 4.77 nm; that of the untreated drug was 18.34 μm. The zeta potential values were acceptable, which indicated suitable stability for formulations. The solubility of the nanosuspensions was up to 5.7-fold higher compared with that of the untreated drug. The results of the ex vivo ocular diffusion of the FLZ nanosuspensions showed the percentage of FLZ penetrating via the goat cornea increased after using Kollicoat to stabilize the nanosuspension formulation. Consequently, when using a nanosuspension formulation of Kollicoat, the antifungal activity of the drug strengthens.

This work aimed to develop a nanosuspension (NSps) as an acetogenin (ACGs) carrier, using soy lecithin (SL) and hydroxypropyl-β-cyclodextrin (βCD) named NSps-βCDSL-ACGs. It was characterized by various spectroscopic techniques (DLS, FTIR, UV-vis diffuse reflectance). Moreover, the NSps morphology was observed by transmission electron microscopy (TEM). Also, the antibacterial activity of NSps-βCDSL-ACGs was evaluated against strains of interest in the poultry sector. NSps-βCDSL-ACGs presented nanometric size (207–239 nm), acceptable polydispersity index (PDI) values (0.13–0.17) and a high Z potential value (−47.17–50.36 mV), demonstrating high stability. The presence of ACGs in NSps-βCDSL-ACGs was confirmed by FTIR analysis. The nanoparticles had a spherical shape and exhibited high inhibition potential against Salmonella Enteritidis (88.18%), Streptococcus gallolyticus (88.01%), Salmonella Typhimurium (86.28%) and Salmonella Infantis (77.02%) strains up to 48 h, and a reduction of up to 3 log CFU/mL was achieved for S. Typhimurium. Therefore, NSps-βCDSL-ACGs is an attractive option for implementing ACGs administration in the poultry sector to reduce the use of antibiotics and minimize bacterial resistance.

The excessive use of synthetic pesticides for pest management is harmful to human health and environment. Plants extract are promising active ingredients to produce safe and ecofriendly biopesticides as an alternative, while their physicochemical properties are a thoughtful issue to generate commercial formulates. Thus, nanotechnology plays an important role to solve this problem. In this study, nanobiopesticides of Moringa oleifera leaves (Moringaceae) were formulated using a polyvinylpyrrolidone stabilizer. The minimum particle size of M. oleifera nanosuspension was 174 nm with polydispersity index and zeta potential values of 0.354 and −13.2 mV, respectively. The morphology of M. oleifera nanobiopesticide was analyzed by scanning electron microscopy which showed spherical to the oval shape particles. The comparative pesticidal efficacy of M. oleifera extract and its nanosuspensions against stored product insects was conducted. The M. oleifera M3 nanosuspension showed significantly (P < 0.05) high insecticidal activity with a mortality rate of 83.00 ± 0.56 and 92.48 ± 3.12% after 72 h against Tribolium castaneum (Coleoptera: Tenebrionidae) and Rhyzopertha dominica (Coleoptera: Bostrichidae), respectively. Conversely, M. oleifera extract exhibited significantly low insecticidal efficacy with a mortality rate of 79.30 ± 2.64 and 81.15 ± 2.97% against Tribolium castaneum and Rhyzopertha dominica, respectively. The prepared nanoformulations showed high pesticidal potential may be suggested as ecofriendly, sustainable, and effective biopesticides against stored product insects. The Moringa oleifera nanobiopesticides showed effective and enhanced pesticidal potential against stored grain insects. [ABSTRACT FROM AUTHOR]

The following research aimed to enhance solubility by loading candesartan cilexetil into nanosuspension. Candesartan cilexetil-loaded nanosuspension was prepared with the aid of Design-Expert® software. A technique of solvent evaporation was employed to produce nanosuspensions from hydroxyl propyl methyl cellulose (HPMC E5), polyvinyl pyrrolidone (PVP K-30), and poloxamer (PXM 188). The optimised nanosuspensions' particle size and polydispersity index (PDI) were 64.65 nm and 0.059, respectively. The entrapment efficacy (EE %) and drug loading (DL %) were 86.75 and 10.17%, respectively. The atomic force microscopy (AFM) revealed spherical and smooth nanoparticles. The Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) revealed pure, crystalline and conjugated drugs inside the nanosuspension. The release study confirmed 90% release within 10 min. No significant changes in particle sizes over three months were found, indicating stable nanoparticles. Saturated solubility of the candesartan cilexetil powder and loaded nanosuspension was 63.3 ± 6 and 344.7 ± 16 µg.ml-1, respectively, revealing more than five times increase in solubility. Candesartan cilexetil-loaded nanosuspensions were successfully prepared using different combinations of PVP K-30, HPMC E-5 and PXM 188 in various concentrations. Solubility was enhanced by loading the payload into nanosuspensions [ABSTRACT FROM AUTHOR]

Kaempferol (KAE) is a naturally occurring flavonoid compound with antitumor activity. However, the low aqueous solubility, poor chemical stability, and suboptimal bioavailability greatly restrict its clinical application in cancer therapy. To address the aforementioned limitations and augment the antitumor efficacy of KAE, we developed a kaempferol nanosuspensions (KAE-NSps) utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a stabilizing agent, screened the optimal preparation process, and conducted a comprehensive investigation of their fundamental properties as well as the antitumor effects in the study. The findings indicated that the particle size was 186.6 ± 2.6 nm of the TPGS-KAE-NSps optimized, the shape of which was fusiform under the transmission electron microscope. The 2% (w/v) glucose was used as the cryoprotectant for TPGS-KAE-NSps, whose drug loading content was 70.31 ± 2.11%, and the solubility was prominently improved compared to KAE. The stability and biocompatibility of TPGS-KAE-NSps were favorable and had a certain sustained release effect. Moreover, TPGS-KAE-NSps clearly seen to be taken in the cytoplasm exhibited a stronger cytotoxicity and suppression of cell migration, along with increased intracellular ROS production and higher apoptosis rates compared to KAE in vitro cell experiments. In addition, TPGS-KAE-NSps had a longer duration of action in mice, significantly improved bioavailability, and showed a stronger inhibition of tumor growth (the tumor inhibition rate of high dose intravenous injection group was 68.9 ± 1.46%) than KAE with no obvious toxicity in 4T1 tumor-bearing mice. Overall, TPGS-KAE-NSps prepared notably improved the defect and the antitumor effects of KAE, making it a promising nanodrug delivery system for KAE with potential applications as a clinical antitumor drug. [ABSTRACT FROM AUTHOR]

The current study focused on the formulation, physicochemical characterization, and antibacterial susceptibility testing of inhalable spray dried powders containing ciprofloxacin (CIP) and polymyxin B sulfate (PMB). CIP nanosuspensions with an average particle diameter of 435.9 ± 9.3 nm were initially obtained using the wet-milling protocol and subsequently co-spray dried with PMB solutions to yield inhalable dry powders. The Powder X-Ray Diffraction (P-XRD) results showed that the wet-milled CIP nanoparticles were in a 4.8 hydrate state, which were transformed to 3.7 hydrates and amorphous materials after co-spray drying. The PMB remained in an amorphous state in the dry powders. Differential Scanning Calorimetry (DSC) analyses revealed that the glass transition temperatures (Tgs) of the co–spray dried formulations were higher than the Tg of CIP, but lower than the Tg of PMB. Fourier Transform Infrared Spectrometer (FTIR) studies suggested the existence of π - π interactions between CIP and PMB in the co-spray dried powders. These powders also retained antimicrobial effects against Pseudomonas aeruginosa strain PAO1. In addition, the spray-dried powder formulations exhibited satisfactory solid-state stability and aerodynamic characteristics when stored under 3% relative humidity and 20 ± 5 °C for 4 months. Overall, the newly developed inhalable CIP/PMB dry powders are a promising therapeutic strategy for respiratory tract infections.

Currently, curcumin still faces issues like low loading capacity and poor absorption performance, limiting its applications in antioxidant performance. Emulsions stabilized with high-load curcumin/octenyl succinic anhydride (OSA) starch nanosuspensions, aiming to enhance the antioxidant activity of algal oil and improve curcumin absorption.The physicochemical properties of emulsions stabilized by curcumin nanosuspensions, the oxidative characteristics of algae oil, and the absorption performance of curcumin were investigated. The crystalline content of curcumin was notably decreased by the media grinding process. Furthermore, the emulsions prepared from nanosuspensions with different curcumin contents exhibited good thermal and centrifugal stability. Importantly, as the curcumin concentration in the emulsions increased, the curcumin content in the micelles also increased, leading to a gradual decrease in the oxidation degree of algal oil. These research findings provide a theoretical basis for the development of curcumin high-loaded nanosuspension emulsion systems and their wide application in the food industry.

The viscosity models for concentrated suspensions of unimodal hard spheres published in the twenty-first century are reviewed, compared, and evaluated using a large pool of available experimental data. The Pal viscosity model for unimodal suspensions is the best available model in that the predictions of this model agree very well with the low (zero)-shear experimental relative viscosity data for coarse suspensions, nanosuspensions, and coarse suspensions thickened by starch nanoparticles. The average percentage error in model predictions is less than 6.5%. Finally, the viscous behavior of concentrated multimodal suspensions is simulated using the Pal model for unimodal suspensions. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second leading neurodegenerative disease globally, impacting the quality of life of millions of people. It is estimated that the treatment cost of PD in the USA can rise to 79 billion dollars by 2037. Limited drugs are approved by USFDA, which only provides symptomatic relief. Further, the drug efficacy is challenged due to low drug-brain concentration due to first-pass metabolism and blood-brain barrier (BBB). Intranasal drug administration can offer several advantages over systemic administration, providing efficient brain delivery. Nose-to-brain (N2B) drug delivery can enhance brain bioavailability, reduce enzymatic degradation, and reduce systemic adverse effects. However, due to poor absorption from the nasal mucosa, intranasal administration can be challenging for hydrophilic drugs. The drug mucociliary clearance, retention time, and nasal enzymatic degradation can also affect N2B drug delivery. Nanocarriers can enhance residence time, improve nasal permeation, increase brain uptake, and reduce enzymatic degradation. This review discusses the roles and applications of various N2B nanocarriers to treat PD effectively. Clinical trials of antiparkinson molecules is also covered. Lastly, safety aspects and prospects of potential nanotherapeutics for the effective treatment of PD are discussed. [Display omitted] [ABSTRACT FROM AUTHOR]

Low water solubility and high permeability present formulation challenges for drugs categorized as Biopharmaceutics Classification System (BCS) Class II, resulting in reduced bioavailability. This research focuses on addressing the solubility issues of BCS Class II drugs, including Simvastatin, Ketoprofen, griseofulvin, ibuprofen, ketoconazole, and carbamazepine, which exhibit high permeability but poor solubility. A potential strategy to improve the solubility and bioavailability of these drugs is the utilization of nanosuspensions. This study investigates the application of nanosuspension technology to enhance the solubility of Ketoprofen, a BCS Class II drug. By reducing the drug's particle size within the nanosuspension, solubility is improved, leading to increased bioavailability and optimized therapeutic efficacy. The research includes in vitro and in vivo experiments to evaluate the drug release profiles and bioavailability of Ketoprofen-loaded nanosuspensions. Significant findings from this research include the demonstration of improved bioavailability and enhanced drug release properties achieved with the nanosuspension formulation. In vitro studies show increased drug dissolution rates and improved release profiles compared to conventional formulations. In vivo experiments reveal enhanced pharmacokinetic parameters and therapeutic effectiveness of Ketoprofen when administered through the nanosuspension. These results highlight the potential of nanosuspensions as an efficient drug delivery system for BCS Class II drugs, addressing their solubility limitations and improving their bioavailability. The findings contribute to the development of novel strategies in pharmacology for enhancing drug solubility and therapeutic outcomes. Overall, this research emphasizes the significance of nanosuspension technology in optimizing the delivery of BCS Class II drugs and offers valuable insights for future formulation development and therapeutic applications. [ABSTRACT FROM AUTHOR]

Nanosuspensions (NSs), which are nanosized colloidal particle systems, have recently become one of the most interesting substances in nanopharmaceuticals. NSs have high commercial potential because they provide the enhanced solubility and dissolution of low-water-soluble drugs by means of their small particle sizes and large surface areas. In addition, they can alter the pharmacokinetics of the drug and, thus, improve its efficacy and safety. These advantages can be used to enhance the bioavailability of poorly soluble drugs in oral, dermal, parenteral, pulmonary, ocular, or nasal routes for systemic or local effects. Although NSs often consist mainly of pure drugs in aqueous media, they can also contain stabilizers, organic solvents, surfactants, co-surfactants, cryoprotectants, osmogents, and other components. The selection of stabilizer types, such as surfactants or/and polymers, and their ratio are the most critical factors in NS formulations. NSs can be prepared both with top-down methods (wet milling, dry milling, high-pressure homogenization, and co-grinding) and with bottom-up methods (anti-solvent precipitation, liquid emulsion, and sono-precipitation) by research laboratories and pharmaceutical professionals. Nowadays, techniques combining these two technologies are also frequently encountered. NSs can be presented to patients in liquid dosage forms, or post-production processes (freeze drying, spray drying, or spray freezing) can also be applied to transform the liquid state into the solid state for the preparation of different dosage forms such as powders, pellets, tablets, capsules, films, or gels. Thus, in the development of NS formulations, the components/amounts, preparation methods, process parameters/levels, administration routes, and dosage forms must be defined. Moreover, those factors that are the most effective for the intended use should be determined and optimized. This review discusses the effect of the formulation and process parameters on the properties of NSs and highlights the recent advances, novel strategies, and practical considerations relevant to the application of NSs to various administration routes. [ABSTRACT FROM AUTHOR]

Cinnamomum zeylanicum is a traditional medicinal plant known for its anti-inflammatory, antidiabetic, antimicrobial, anticancer, and antioxidant properties. Its therapeutic efficacy using nanosuspensions is still unclear for treating infectious diseases. This study was designed to evaluate the bioactivities, biochemical characterization, and bioavailability of freshly prepared nanosuspensions of C. zeylanicum. Structural and biochemical characterization of C. zeylanicum and its biological activities, such as antioxidants, antimicrobials, antiglycation, α-amylase inhibition, and cytotoxicity was performed using Fourier-transform infrared (FTIR) spectroscopy and High-Performance Liquid Chromatography (HPLC). C. zeylanicum extract and nanosuspensions showed TPCs values of 341.88 and 39.51 mg GAE/100 g while showing TFCs as 429.19 and 239.26 mg CE/100g, respectively. DPPH inhibition potential of C. zeylanicum extract and nanosuspension was 27.3% and 10.6%, respectively. Biofilm inhibition activity revealed that bark extract and nanosuspension showed excessive growth restraint against Escherichia coli, reaching 67.11% and 66.09%, respectively. The α-amylase inhibition assay of extract and nanosuspension was 39.3% and 6.3%, while the antiglycation activity of nanosuspension and extract was 42.14% and 53.76%, respectively. Extracts and nanosuspensions showed maximum hemolysis at 54.78% and 19.89%, respectively. Results indicated that nanosuspensions possessed antidiabetic, antimicrobial, anticancer, and antioxidant properties. Further study, however, is needed to assess the clinical studies for the therapeutic use of nanosuspensions.

Nanomilling technique has been a growing interest in the field of nanotechnology for effective and efficient production of nanoparticles. It has been found to be advantageous over other chemical and physical methods owing to toxicity, chemical retainability and structural composition. Especially in the case for biomaterials, where many natural bio-products are poorly water-soluble, nanomilling has been proved to be a validated process for reducing the particle-size. This study has focussed on wet-stirred media milling, a top-down approach for the preparation of nanoparticles of two natural bio-based polymers, which are used extensively in the research world—starch and cellulose. Different parameters have been optimized for the production of smallest-sized nanoparticles and a comparative study has been discussed to understand the process of grinding of particles. Particle Size Analyser has been used to check the trend of change in size at different milling-time. The size and morphology of the particles were confirmed by microscopy tests, with chemical and structural changes of materials examined from FTIR and XRD techniques. The nanoparticles for respective biomaterials were prepared successfully from this method and a detailed comparative investigation has been presented in this study. [ABSTRACT FROM AUTHOR]

Aim: To develop quercetin nanocrystals by a simple approach and to evaluate their in vivo antifibrotic efficacy. Materials & methods: Nanosuspensions were fabricated by a thin-film hydration technique and ultrasonication. The influence of process variables on the average diameter of quercetin nanoparticles was investigated. Moreover, in vivo efficacy was investigated in an established murine CCl4-induced fibrosis model. Results: Nanocrystals showed a particle size of <400 nm. The optimized formulations showed an increase in dissolution rate and solubility. Quercetin nanocrystals markedly prevented fibrotic changes in the liver, as evidenced by mitigated histopathological changes and diminished aminotransferase levels and collagen accumulation. Conclusion: The findings reflect the promising potential of quercetin nanocrystals for liver fibrosis prevention. [ABSTRACT FROM AUTHOR]

This study aimed to formulate the green, sustainable, and ecofriendly nanobiopesticides of Azadirachta indica with enhanced pest control efficacy. Nanoprecipitation method was used for the development of nanobiopesticides. Optimisation was done by response surface methodology. Nanoformulations were characterised by zetasizer, scanning electron microscopy, energy dispersive x-ray spectroscopy, atomic force microscopy, and Fourier transform infrared spectroscopy. Pesticidal potential of nanosuspensions was evaluated by insecticide impregnated filter paper method. Optimised nanobiopesticide showed an average particle size of 275.8 ± 0.95 nm, polydispersity index (PDI) 0.351 ± 0.002, and zeta potential of –33 ± 0.90 mV. Nanobiopesticides exhibited significantly higher mortality rates of 86.81 ± 3.04 and 84.97 ± 2.83% against Tribolium castaneum and Ryzopertha dominica, respectively, as compared to their crude extract. Minor change in particle size from 275.8 ± 0.95 to 298.8 ± 1.00 nm and PDI from 0.351 ± 0.002 to 0.445 ± 0.02 were observed after 3 months of storage at 4 °C. Pesticidal efficacy of A. indica was significantly enhanced by the formulation of its nanobiopesticides. [ABSTRACT FROM AUTHOR]

[Display omitted] Fungal nail infection (Onychomycosis) often requires prolonged treatment and is associated with a high risk of resistance to treatment. Here in this contribution, we introduce a novel approach to enhance penetration and antifungal activity of the antifungal drug griseofulvin (GF). Solid dispersions were prepared with hydroxypropyl methylcellulose acetate succinate (HPMCAS) and combined with surfactant (either sodium dodecyl sulphate (SDS), dodecyl trimethylammonium bromide (DTAB), or Pluronic F127) using mechanochemical activation. The prepared powders were then suspended with spray-dried silica-coated silver nanoparticles and applied onto infected bovine hooves to assess permeability and antifungal activity. The results showed that the prepared nanosuspensions significantly suppressed fungal activity causing disruption of fungal biofilms. Raman mapping showed enhanced permeation while dynamic vapor sorption (DVS), and particle size measurements showed varied effects depending on the type of surfactant and milling conditions. The prepared nanosuspensions displayed enhanced solubility of the poorly soluble drug reaching approximately 1.2 mg/mL. The results showed that the dispersions that contained DTAB displayed maximum efficacy while the inclusion of colloidal silver did not seem to significantly improve the antifungal activity compared to other formulations. [ABSTRACT FROM AUTHOR]

[Display omitted] • Developing a size-controlled method for the preparation of andrographolide suspensions. • Demonstrating both in vitro and in vivo behaviors of andrographolide suspensions with different particle sizes. • Providing evidence for the size effect of andrographolide suspensions on their IVIVC performance in oral absorption. The study aimed to explore the size effect on the in vitro-in vivo correlation (IVIVC) in the oral absorption of andrographolide nanosuspensions (Ag-NS). Ag-NS with controllable particle sizes were prepared by ultrasonic dispersion method, and the formulation and process parameters were optimized through single factor experiments using mean particle size, polydispersity index, and stability as evaluation indicators. The morphology of Ag-NS was observed by scanning electron microscopy (SEM), and the crystalline state of the nanosuspensions was characterized by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). The dissolution tests were carried out with the paddle method in two different mediums simulating the pH conditions in intestinal fluid (pH 6.8) and gastric fluid (pH 1.2), respectively. The pharmacokinetic behaviors were investigated in rats after oral administration, and a deconvolution approach was introduced to determine the correlation between in vitro dissolution and in vivo absorption (IVIVC). The formulation with the use of lecithin and PEG-800 as stabilizers showed its potential in the size-controllable preparation of Ag-NS. Via altering the ultrasonication amplitude and time, three Ag-NS suspensions with three particle sizes, i.e., Ag-NS 250 (249.8 ± 1.3 nm), Ag-NS 450 (485.2 ± 3.7 nm), Ag-NS 1000 (1015 ± 36.1 nm) were prepared. Their morphological and crystal characteristics were not changed during the size reduction process, but both of their in vitro dissolution and in vivo absorption were improved. Relatively better IVIVC performance was observed with the in vitro dissolution data at pH 6.8 (r > 0.9). With the reduction of particle size, the in vivo absorption fraction was more closed to the level of the in vitro dissolution. In conclusion, the decrease in particle size would improve the dissolution and absorption of Ag-NS, and also affect their IVIVC performance. The study would facilitate the design and quality control of Ag-NS in terms of particle size and dissolution specifications. [ABSTRACT FROM AUTHOR]

Digital twins capacitate the industry 4.0 paradigm by predicting and optimizing the performance of physical assets of interest, mirroring a realistic in-silico representation of their functional behaviour. Although advanced digital twins set forth disrupting opportunities by delineating the in-service product and the related process dynamic performance, they have yet to be adopted by the pharma sector. The latter, currently struggles more than ever before to improve solubility of BCS II i.e., hard-to-dissolve active pharmaceutical ingredients by micronization and subsequent stabilization. Herein we construct and functionally validate the first artificially intelligent digital twin thread, capable of describing the course of manufacturing of such solidified nanosuspensions given a defined lifecycle starting point and predict and optimize the relevant process outcomes. To this end, we referenced experimental data as the sampling source, which we then augmented via pattern recognition utilizing neural network propagations. The zeta-dynamic potential metrics of the nanosuspensions were correlated to the interfacial Gibbs energy, while the density and heat capacity of the material system was calculated via the Saft-γ-Mie statistical fluid theory. The curated data was then fused to physical and empirical laws to choose the appropriate theory and numeric description, respectively, before being polished by tuning the critical parameters to achieve the best fit with reality. [ABSTRACT FROM AUTHOR]

Nanosuspensions, as a new drug delivery system for insoluble drugs, are only composed of a drug and a small amount of stabilizer, which is dispersed in an aqueous solution with high drug-loading, small particle size, high dispersion, and large specific surface area. It can significantly improve the dissolution, bioavailability, and efficacy of insoluble drugs. In this study, paclitaxel nanosuspensions ((PTX)NS) were prepared by an ultrasonic precipitation method, with the characteristics of simple preparation and easy repetition. With the help of a homologous targeting mechanism, a kind of glioma C6 cancer cell membrane (CCM)-coated (PTX)NS was developed and modified with DWSW peptide to obtain DWSW-CCM-(PTX)NS with the functions of BBB penetration and tumor targeting. The results showed that the cancer cell membrane could effectively camouflage the nanosuspensions so that it was not cleared by the immune system and could cross the blood-brain-barrier (BBB) and selectively target tumor tissues. Cell uptake experiments and in vivo imaging confirmed that the uptake of DWSW-CCM-(PTX)NS by tumor cells and the distribution in intracranial gliomas increased. Cytotoxicity test and in vivo anti-glioma studies showed that DWSW-CCM-(PTX)NS could significantly inhibit the growth of glioma cells and significantly prolong the survival time of glioma-bearing mice. Finally, the cancer cell membrane coating endowed the nanosuspensions with the biological properties of homologous adhesion and immune escape. This study provides an integrated solution for improving the targeting of nanosuspensions and demonstrates the encouraging potential of biomimetic nanosuspensions applicable to tumor therapy.

[Display omitted] Poor aqueous solubility of preexisting and emerging drug molecules is a common issue faced in the field of pharmaceutics. To address this, particle size reduction techniques, including drug micro- and nanonisation have been widely employed. Nanocrystals (NCs), drug particles with particle sizes below 1 µm, offer high drug content, improved dissolution, and long-acting capabilities. Media milling is the most used method to prepare NCs using of-the-shelf machinery, both at the laboratory and industrial scales. However, early NCs development, especially when limited amounts of the active are available, require the use of milligram-scale media milling. This study introduces a novel mini-scale milling device (Mini-mill) that incorporates temperature control through a water-cooled jacket. The device was used to produce NCs of three model hydrophobic drugs, itraconazole, ivermectin and curcumin, with lowest particle sizes of 162.5 ± 0.4 nm, 178 ± 2 nm, and 116.7 ± 0.7 nm, respectively. Precise control of milling temperature was achieved at 15, 45, and 75°C, with drug dependent particle size reduction trends, with no adverse effects on the milling materials or polymorphic changes in the NCs, as confirmed by calorimetric analysis. Finally, a scale-up feasibility study was carried out in a lab-scale NanoDisp®, confirming that the novel Mini-mills are a material-efficient tool for early formulation development, with potential for scale-up to commercial mills. [ABSTRACT FROM AUTHOR]

Ultrasonication (US) is a modern technology that is routinely applied for a variety of laboratory tasks, from cleaning contaminants inside pores and cracks, to dispersion of solids, particle size reduction, emulsification, chemical reactions, and even cell disruption. It is fast, clean, affordable, and safe, requires minimal space and can be operated as a batch or a continuous process. In the last few decades, a number of articles have been published reporting the use of US as a single method or in combination with others for the nanosizing drug formulations aiming at solubility and permeability improvement. In this review, the different application modes and the principles of operation of the relevant apparatuses are presented. The effects of processing parameters on the efficiency of the method are described in association with the characteristics of the sonicated dispersion. In the last sections, the application of US in the pharmaceutical field is demonstrated by many examples which prove its capability to assist with bioavailability and therapeutic problems by presenting the drugs as nanosized formulations for different routes of administration. [ABSTRACT FROM AUTHOR]

The production of nanosuspensions of poorly soluble active pharmaceutical ingredients (API) is a popular technique to counteract challenges regarding bioavailability of such active substances. A subsequent drying of the nanosuspensions is advantageous to improve the long-term stability and the further processing into solid oral dosage forms. However, associated drying operations are critical, especially with regard to nanoparticle growth, loss in redispersibility and associated compromised bioavailability. This work extends a previous study regarding the applicability of an API (itraconazole) nanosuspension as a granulation liquid in a fluidized bed process with focus on the influence of applied formulation parameters on the structure of obtained nanoparticle-loaded granules and their nanoparticle redispersibility. Generally, a higher dissolution rate of the carrier material (glass beads, lactose, mannitol or sucrose) and a higher content of a matrix former/hydrophilic polymer (PVP/VA or HPMC) in the granulation liquid resulted in the formation of coarser and more porous granules with improved nanoparticle redispersibility. HPMC was found to have advantages as a polymer compared with PVP/VA. In general, a better redispersibility of the nanoparticles from the granules could be associated with better dispersion of the API nanoparticles at the surface of the granules as deduced from the thickness of nanoparticle-loaded layers around the granules. The layer thickness on granules was assessed by means of confocal Raman microscopy. Finally, the dispersion of the nanoparticles in the granule layers was exemplarily described by calculation of theoretical mean nanoparticle distances in the granule layers and was correlated with data obtained from redispersibility studies. [ABSTRACT FROM AUTHOR]

It has recently been reported that lanosterol (LAN) plays a preventive role against lens opacification through the reversal of crystalline aggregation. However, the effect of LAN is not sufficient to restore lens transparency. In this study, we designed ophthalmic nanosuspensions (LAN-ONSs and NIL-ONSs) based on LAN and nilvadipine (NIL), which can counteract cataract-related factors (e.g., enhanced Ca2+ and calpain levels), and investigated whether the combination of LAN-ONSs and NIL-ONSs can restore the nuclear lens opacity in sodium-selenite-induced cataractic rats (cataractic rats). The mean particle sizes of the LAN-ONSs and NIL-ONSs were 108.8 nm and 89.0 nm, respectively. The instillation of the LAN-ONSs or NIL-ONSs successfully delivered the drugs (LAN or NIL) into the lenses of the rats, although the instillation of LAN-ONSs or NIL-ONSs alone did not increase lens transparency in the cataractic rats. On the other hand, the cataract-related factors (enhanced Ca2+ and calpain levels) were significantly alleviated by the combination of LAN-ONSs and NIL-ONSs; furthermore, the perinuclear refractile ring in the lens nucleus and enhanced number of swollen fibers were attenuated by the LAN-ONS and NIL-ONS combination. Moreover, the opacity levels in the cataractic rats were reduced after treatment with the combination of LAN-ONSs and NIL-ONSs. It is possible that the combination of LAN and NIL will be useful for the treatment of lens opacification in the future. [ABSTRACT FROM AUTHOR]

Quercetin-loaded nanosuspensions (Que-NSps) added metabolic inhibitors were evaluated as drug delivery system to promote the oral bioavailability of quercetin. Que-NSps were prepared respectively using d-alpha tocopherol acid polyethylene glycol succinate (TPGS) or Soybean Lecithin (SPC) as stabilizer. On the basis, Piperine (Pip) or sodium oleate (SO) was, respectively, encapsulated in Que-NSps as phase II metabolic inhibitors. The resulting Que-NSps all displayed a mean particle size of about 200 nm and drug loading content was in the range of 22.3–27.8%. The release of quercetin from Que-NSps was slow and sustained. After oral administration of 50 mg/kg different Que-NSps, the levels of free quercetin in plasma were significantly promoted, the concentration of quercetin metabolites (isorhamnetin and quercetin 3-O-β-d-Glucuronide) were decreased. The absolute bioavailability was, respectively 15.55%, 6.93%, 12.38%, and 23.58% for TPGS-Que-NSps, TPGS-SO-Que-NSps, SPC-Que-NSps, and SPC-Pip-Que-NSps, and 3.61% for quercetin water suspension. SPC-Pip-Que-NSps turned out to an ideal nanocarrier combined nano drug delivery system together with metabolic inhibitor to promote oral absorption of quercetin.

The poor aqueous solubility of many approved drugs and most new chemical entities poses a challenge to drug delivery scientists working in academic and industrial labs. Despite the high pharmacological activity these drugs may have, their limited water solubility leads to poor absorption and consequently to sub-therapeutic drug concentrations in target tissues. The formulation of drug nanocrystals (NCs) has emerged as one the most promising approaches for increasing the biopharmaceutical performance of hydrophobic drugs. Initially aimed at increasing the absorption of drugs administered orally, NCs have been increasingly utilised to allow drug delivery via multiple routes, namely, parenteral injections, transdermal, ocular, intranasal, and pulmonary. This review aims to describe the recent progress in the field and demonstrate how the NCs technology enabled the delivery of hydrophobic drugs through multiple administration routes. [Display omitted] [ABSTRACT FROM AUTHOR]

Yingchong Chen,1 Yuling Liu,2 Jin Xie,1 Qin Zheng,1 Pengfei Yue,1 Liru Chen,3 Pengyi Hu,1 Ming Yang1 1Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, People’s Republic of China; 2Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of China; 3Beijing Hospital, Beijing 100730, People’s Republic of ChinaCorrespondence: Pengfei Yue; Ming YangKey Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, 1688 Meilingdadao Road, Nanchang 330004, People’s Republic of ChinaTel/ Fax +86 791 8711 8658Email ypfpharm@126.com; yangming_215@163.comPurpose: Nose-to-brain drug delivery is an effective approach for poorly soluble drugs to bypass the blood–brain barrier. A new drug intranasal delivery system, a nanosuspension-based in situ gel, was developed and evaluated to improve the solubility and bioavailability of the drug and to prolong its retention time in the nasal cavity.Materials and Methods: Breviscapine (BRE) was chosen as the model drug. BRE nanosuspensions (BRE-NS) were converted into BRE nanosuspension powders (BRE-NP). A BRE nanosuspension in situ gelling system (BRE-NG) was prepared by mixing BRE-NP and 0.5% gellan gum (m/v). First, the BRE-NP were evaluated in terms of particle size and by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Subsequently, the critical ionic concentration of the gellan gum phase transition, influence of the deacetylated gellan gum (DGG) concentration on the expansion coefficient (S%), water-holding capacity, rheological properties and in vitro release behaviour of the BRE-NG were investigated. The pharmacokinetics and brain distribution of the BRE-NG after intranasal administration were compared with those of the intravenously injected BRE-NP nanosuspensions in rats.Results: The rheology results demonstrated that BRE-NG was a non-Newtonian fluid with good spreadability and bioadhesion performance. Moreover, the absolute bioavailability estimated for BRE-NG after intranasal administration was 57.12%. The drug targeting efficiency (DTE%) of BRE in the cerebrum, cerebellum and olfactory bulb was 4006, 999 and 3290, respectively. The nose-to-brain direct transport percentage (DTP%) of the cerebrum, cerebellum and olfactory bulb was 0.975, 0.950 and 0.970, respectively.Conclusion: It was concluded that the in situ gel significantly increased the drug retention time at the administration site. Therefore, the nanosuspension-based in situ gel could be a convenient and effective intranasal formulation for the administration of BRE.Keywords: nose-to-brain, nanosuspensions, in situ gel, breviscapine, brain distribution