Physical Stability Research Articles

Regulating effects of beet pectin on the stability and 3D printing performance of high internal phase pickering emulsions stabilized by lactoferrin-EGCG

This study aimed to develop lactoferrin-polyphenol-polysaccharide (LF-EGCG-BP) ternary covalent complexes to improve the stability and 3D printing performance of fish oil high internal phase emulsions (HIPEs) stabilized by lactoferrin-polyphenol (LF-EGCG) binary covalent complex. The effects of beet pectin (BP) on the physicochemical properties, structure, interfacial behavior, rheological properties and stability of LF-EGCG HIPEs were investigated. Results showed that the fluorescence quenching mechanism of BP on LF-EGCG was static quenching. BP (especially at 20:1 (w/w)) efficiently improved the stability of LF-EGCG HIPEs by enhancing the mechanical property of interfacial films and network structure. After the addition of BP, the droplet size of HIPEs was reduced, lipid oxidation stability, physical stability, and multiple light scattering stability were increased. Raman spectra showed that the interaction between oil phase and aqueous phase of HIPEs was enhanced after the introduce of BP. The free fatty acids (FFA) release in HIPEs stabilized by LF-EGCG-BP was decreased. Meanwhile, BP increased the viscoelasticity, recovery and gel strength of HIPEs, giving the HIPE inks better 3D printing integrity and clarity.

Doubly self-assembled dermatan sulfate/chitosan nanoparticles for targeted siRNA delivery in cancer therapy

RNA interference, a naturally occurring regulatory mechanism in which small interfering RNA (siRNA) molecules are responsible for the sequence-specific suppression of gene expression, emerged as one of the most promising gene therapies in cancer. In this work, we investigate a microfluidics double self-assembly method based on micellization and polyelectrolyte complex formation for the encapsulation of siRNA targeting the BIRC5 gene, a member of the inhibitor of apoptosis gene family, that codes for survivin a protein of theinhibitorof apoptosis protein family that is involved in triple-negative breast cancer (TNBC) proliferation and metastasis within nanoparticles of an amphiphilic chitosan-graft-poly(methyl methacrylate) copolymer and low-molecular weight dermatan sulfate, a polysaccharide targeting the CD44 receptor overexpressed in this tumor. Nanoparticles are spherical and display a hydrodynamic diameter of ∼ 200 nm, as measured by dynamic light scattering and scanning electron microscopy. In addition, these colloidal systems exhibit a strongly negative zeta-potential that confers them excellent physical stability for at least four months owing to electrostatic repulsion and evidences the exposure of the polyanionic dermatan sulfate on the surface. The key role of dermatan sulfate in the active targeting and intracellular delivery of the cargo in the murine breast cancer cell line 4T1, a model of TNBC, is confirmed by confocal laser scanning microscopy and imaging flow cytometry. Finally, the silencing efficiency is demonstrated in 4T1 cell viability, migration, proliferation and spheroid formation assays in vitro. Overall results highlight the promise of this simple, reproducible and scalable method for the nanoencapsulation of siRNA and other therapeutic nucleic acids.

Valsartan/2-Aminopyridine Co-Amorphous System: Preparation, Characterization, and Supramolecular Structure Simulation by Density Functional Theory Calculation.

The objective of this work was to improve the solubility and discover a stable co-amorphous form of valsartan (VAL), a BCS class-II drug, by utilizing small molecule 2-Aminopyridine (2-AP) in varying molar ratios (2:1, 1:1, and 1:2), employing a solvent evaporation technique. Additionally, by way of a density functional theory (DFT)-based computational method with commercially available software, a new approach for determining the intermolecular connectivity of multi-molecular hydrogen bonding systems was proposed. The binary systems' features were characterized by PXRD, DSC, FTIR, and Raman spectroscopy, while the equilibrium solubility and dissolution was determined in 0.1 N HCL and water conditions to investigate the dissolution advantage of the prepared co-amorphous systems. The results demonstrated that the co-amorphous system was successfully prepared in VAL/2-AP with a 1:2 molar ratio following solvent evaporation, whereby the hydrogen bonding sites of VAL were fully occupied. Physical stability studies were carried out under dry conditions at room temperature for 6 months. Furthermore, four possible ternary systems were constructed, and their vibrational modes were simulated by DFT calculations. The calculated infrared spectra of the four configurations varied widely, with trimer 1 showing the most resemblance to the experimental spectrum of the co-amorphous 1:2 system. Additionally, co-amorphous VAL/2-AP displayed significant improvement in the solubility and dissolution study. Notably, in the 1:2 ratio, there was almost a 4.5-fold and 15.6-fold increase in VAL's solubility in 0.1 N HCL and water environments, respectively. In conclusion, our findings highlight the potential of co-amorphous systems as a feasible approach to improving the properties and bioavailabilities of insoluble drugs. The proposed simulation method provides valuable insights into determining the supramolecular structure of multi-molecular hydrogen bonding systems, offering a novel perspective for investigating such systems.

"The More, the Better?": The Impact of Sugar-to-Protein Molar Ratio in Freeze-Dried Monoclonal Antibody Formulations on Protein Stability.

Lyophilization is widely used to ensure the stability of protein drugs by minimizing chemical and physical degradation in the dry solid state. To this end, proteins are typically formulated with sugars that form an amorphous immobilizing matrix and stabilize hydrogen bonds replacing water molecules. The optimal amount of sugar required and protein stability at low excipient-to-protein molar ratios are not well understood. We investigated this by focusing on the physical stability of formulations, reflecting highly concentrated monoclonal antibody (mAb) lyophilizates at low sucrose to mAb ratios between 25:1 and 360:1. Additionally, the impact of different excipient types, buffer concentrations, and polysorbates was studied. The mAb stability was evaluated over up to three months at 25 and 40 °C. We investigated the "the more, the better" approach regarding excipient usage in protein formulation and the existence of a potential stabilizing threshold. Our findings show efficient monomeric content preservation even at low molar ratios, which could be explained based on the water replacement theory. We identified an exponential correlation between the sucrose to protein molar ratio and aggregate formation and found that there is no molar ratio threshold to achieve minimum stabilization. Sucrose demonstrated the best stabilization effect. Both mannitol, used as a cryoprotectant at low concentrations, and arginine reduced aggregation compared to the pure mAb formulation. The higher ionic strength of 5 mM histidine buffer enhanced protein stability compared to that of 0.1 mM histidine buffer, which was more pronounced at lower molar ratios. The addition of polysorbate 20 contributed an additional interfacial stabilizing effect, complementing the cryoprotective and lyoprotective properties of sucrose. Overall, a model could be developed to optimize the quantity of sugar required for protein stabilization and facilitate a more rational design of protein lyophilizates. The molar ratio of sugar to protein for high-concentration mAb products is limited by the acceptable tonicity, but we showed that sufficient stabilization can be achieved even at low molar ratios.

High-Energy Fluidic Microfluidizer Produced Whole Germinant Oat Milk: Effects on Physical Properties and Nutritional Quality.

Whole oat milk (WOM) was prepared from germinated oat by an innovatively designed high-energy fluidic microfluidizer (HEFM). The results indicated that germination treatment significantly raised the content of total protein, γ-aminobutyric acid, total phenolics, and reducing sugar, while it decreased the content of total starch and β-glucan. Oat with a germination time of 48 h had the best nutritional quality for producing WOM. The physical stability of the WOM prepared from germinated oat was effectively improved by HEFM treatment. The apparent viscosity increased, the instability index reduced from 0.67 to 0.37, and the precipitate weight ratio decreased from 13.54% to 9.51%. As the pressure of the HEFM increased from 0 to 120 MPa, the particle size decreased from 169.5 to 77.0 µm, which was helpful to improve the physical stability of the WOM. Meanwhile, the color of the WOM became whiter after the HEFM treatment. The content of β-glucan and soluble protein in the WOM significantly increased, which was due to the disruption of cells by the HEFM processing. The optimal HEFM pressure for WOM production is 120 MPa. This study provided a new way to produce whole oat milk with a high nutritional quality and good physical properties.

The Role of Phase Separation and Local Mobility in the Stabilization of a Lyophilized IgG2 Formulation.

The utility of employing solid-state NMR (SSNMR) to assess parameters governing the stability of a lyophilized IgG2 protein was the focus of the present work. Specifically, the interaction between the sugar stabilizer (sucrose) and protein component was measured using SSNMR and compared to physical and chemical stability data obtained from thermally stressed samples. 1H T1 and 1H T1⍴ relaxation times were measured by SSMNR for 5 different formulation conditions, and the resultant values were used to examine local mobility and phase separation, respectively. From the SSNMR measurements, it was found local mobility decreased as the sucrose to protein weight ratio increased. The decrease in local mobility corresponded to an increase in storage stability (both chemical and physical) of the lyophilized solids up to a critical weight ratio of sucrose to protein. Additionally, 1H T1⍴ measurements obtained on formulations having higher protein to sucrose weight ratios indicated phase separation of the protein and sucrose phases was occurring, at least on a small scale. Along with an increase in local mobility, phase separation in these specific formulations is thought to have played a role in their decreased storage stability in the solid state.

Rapid prediction of key residues for foldability by machine learning model enables the design of highly functional libraries with hyperstable constrained peptide scaffolds.

Peptides are an emerging modality for developing therapeutics that can either agonize or antagonize cellular pathways associated with disease, yet peptides often suffer from poor chemical and physical stability, which limits their potential. However, naturally occurring disulfide-constrained peptides (DCPs) and de novo designed Hyperstable Constrained Peptides (HCPs) exhibiting highly stable and drug-like scaffolds, making them attractive therapeutic modalities. Previously, we established a robust platform for discovering peptide therapeutics by utilizing multiple DCPs as scaffolds. However, we realized that those libraries could be further improved by considering the foldability of peptide scaffolds for library design. We hypothesized that specific sequence patterns within the peptide scaffolds played a crucial role in spontaneous folding into a stable topology, and thus, these sequences should not be subject to randomization in the original library design. Therefore, we developed a method for designing highly diverse DCP libraries while preserving the inherent foldability of each scaffold. To achieve this, we first generated a large-scale dataset from yeast surface display (YSD) combined with shotgun alanine scan experiments to train a machine-learning (ML) model based on techniques used for natural language understanding. Then we validated the ML model with experiments, showing that it is able to not only predict the foldability of peptides with high accuracy across a broad range of sequences but also pinpoint residues critical for foldability. Using the insights gained from the alanine scanning experiment as well as prediction model, we designed a new peptide library based on a de novo-designed HCP, which was optimized for enhanced folding efficiency. Subsequent panning trials using this library yielded promising hits having good folding properties. In summary, this work advances peptide or small protein domain library design practices. These findings could pave the way for the efficient development of peptide-based therapeutics in the future.

Chitozan-zeolite Composite Fertilizer Formulations for Enhancing Nutrient Use Efficiency

The experiment was carried out in the Department of Soil Science and Agricultural Chemistry at the College of Agriculture, Vellayani, Kerala, from January to May 2024. Slow release fertilizer formulations (SRF) containing all the major (N, P,K), secondary (Ca, Mg, S) and micronutrients (Zn, B) were prepared using compatible fertilizer materials(urea, diammonium phosphate, muriate of potash, phosphogypsum, magnesium sulphate, zinc sulphate and borax), carrier materials (zeolite and chitosan) which are mixed in five ratios (1:1,1:2,1:3,2:1,3:1) and prepared by two methods namely solid impregnation and solute impregnation. Ten formulations were prepared with different combinations of fertilizer mix, carrier materials and impregnation methods. These formulations were prepared to meet the specific nutrient needs of solanaceous crops (75:40:25 N:P:K kgha-1) and the soil nutrient status. The formulations were characterized for their physical (hygroscopicity, moisture content and stability) and electro-chemical properties (pH, EC) and observed that they are non hygroscopic, non caking and are highly stable. The moisture content of formulations ranged from 2.57 % to 3.92 %, pH 6.30 to 6.81 and EC 10.06 to 16.29 dS m-1. The nutrient content in these formulations were 10.21 to 12.02 % nitrogen, 3.82 to 4.63 % phosphorus, 2.65 to 5.28 % potassium, 5.58 to 6.58 % calcium, 2.46 to 3.08% magnesium, 2.58 to 3.46% sulphur, 1.06 to 1.23% zinc and 0.15 to 0.24% boron. The highest nutrient content was obtained in formulation containing fertilizer mix + C-Z (1:1) prepared by solid impregnation method.

Formulasi dan Uji Aktivitas Anti-aging Sediaan Hand Cream yang Mengandung Ekstrak Etanol Kulit Buah Nanas (Ananas comosus (L.) Merr.)

Hand skin that is often exposed to the sun easily loses moisture and is more rough. Hand cream is a care product that is applied to the palms and backs of the hands that can help restore hydration and skin function due to dry and rough skin. Pineapple peel contains flavonoids, vitamin C, and bromelain enzymes that has potential to be formulated into anti-aging preparations. This research aims to formulate ethanol extract of pineapple peel (Ananas comosus (L.) Merr.) into hand cream and to test the effectiveness as anti-aging agent. This research included making extracts by percolation method using 70% ethanol solvent, testing the antioxidant activity of pineapple peel extract using DPPH method, and hand cream formulations with the addition of pineapple peel extract with respective concentration of 0% (F0), 5% (F1), 7.5% (F2), and 10% (F3). Evaluation of hand cream preparations included organoleptic test, homogeneity, emulsion type, pH, viscosity, and physical stability at room temperature storage for 12 weeks and cycling test. Anti-aging effectiveness testing was carried out during the 4 weeks treatment period, by measuring parameters such as moisture, pores, blemishes and wrinkles on the skin of the backs of volunteers' hands which were measured once a week using a skin analyzer. The results of the antioxidant activity test of the ethanol extract of pineapple peel were included in the strong category with an IC50 value of 88.21 µg/mL. The hand cream preparation produced was homogeneous, O/W emulsion type, pH value 5.09-6.56, viscosity value 4086.76-6104.96 cPs, stable during 12 weeks of storage at room temperature and stable in the cycling test for 4 weeks. Hand cream preparations with a concentration of 10% have better effectiveness than 0%, 5% and 7.5% which results in an average percent moisture recovery of 77.60%, pores 62.92%, blemishes 55.65%, and wrinkles 45.92%.

Addition of polyphenolic extracts of Myrtus communis and Arbutus unedo fruits to whey: valorization of a common dairy waste product as a functional food.

Whey, a nutrient-rich byproduct of the dairy sector, possesses high potential for creating novel nutraceutical products. The present study investigates a potential new functional food by incorporating polyphenolic extracts from Myrtus communis and Arbutus unedo fruits into whey in both liquid (LA) and powder (PA) addition forms. Chemical, microbiological, physical stability and antioxidant activity were monitored for 60 days (from T0 to T60). Both LA and PA of fruit extracts remained chemically stable for the whole period, except for A. unedo PA, which showed a decline in polyphenols after T45. Enriched whey samples showed higher antioxidant activity than pure whey. Microbiological analysis revealed the presence of lactic acid bacteria, indicating potential prebiotic effects. However, the high tannin concentration of A. unedo extracts partially modified the casein micelle structure. Whey enriched with Mediterranean fruit extracts shows great potential as a functional food, combining the benefits of plant antioxidants, probiotic bacteria and good stability. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Formulation, Development and Evaluation of Pulsatile Tablets of Etoricoxib

Aim: This research aimed to develop a pulsatile drug delivery system (PDDS) for etoricoxib, selective COX-2 inhibitor analgesic, to address the limitations of conventional formulations by releasing the drug at specific intervals aligned with the circadian rhythm of pain. Method: Core tablets containing Etoricoxib were prepared by direct compression with varied concentrations of croscarmellose sodium as a superdisintegrant. The optimized core tablets were coated using hydrophilic (HPMC K4M) and hydrophobic (ethyl cellulose) polymers in different ratios to create press-coated pulsatile tablets with varying lag times. Physical properties hardness, thickness, friability, and disintegration, drug content uniformity, and in vitro release were evaluated. Results: The core tablets exhibited rapid drug release, with batch C3 showing 98.61% release within 60 minutes. Press-coated formulations with different polymer ratios exhibited varying lag times, with batch F3 achieving the optimal balance—providing a 4-hour lag time and 96.6% drug release over 8 hours. Stability studies confirmed the physical and chemical stability of the optimized formulation (F3) over 6 months under accelerated conditions. Conclusion: The developed press-coated pulsatile tablets of etoricoxib successfully achieved a controlled lag time and sustained drug release profile, making them suitable for chronopharmacological management of pain. Keywords: Etoricoxib, Pulsatile Drug Delivery System, Chronopharmacology, Press-Coated Tablets. etc

Radiation-induced nanogel engineering based on pectin for pH-responsive rutin delivery for cancer treatment.

This research investigates the formulation of a nanogel complex using pectin and poly(acrylic acid) (PAAc) to encapsulate rutin. The nanogel's pH-responsive behavior and its potential as a targeted drug delivery platform are investigated. The gamma irradiation-induced crosslinking mechanism is elucidated, highlighting its role in creating a stable three-dimensional network structure within the polymer matrix. Fourier transform infrared spectroscopy analysis sheds light on the molecular interactions within rutin and the nanogel-rutin complex. The pH-responsive behavior of the nanogel is explored, showcasing its ability to release rutin selectively in response to pH variations and displaying high physical and chemical stability. Transmission electron microscopy imaging provides visual insights into nanogel morphology and interactions. The cumulative drug content from the nanogel was 86.14 ± 2.61%. The pH-dependent release profile of the nanogel was examined, demonstrating selective rutin release in response to varying pH levels. Cytotoxicity studies were conducted against four human cancer cell lines-HepG2, A549, MCF-7, and HCT-116 showing significant reductions in IC50 values, indicating enhanced therapeutic efficacy. Additionally, molecular docking studies revealed strong binding interactions of rutin with VEGFR-2 and EGFRT790M. Our nanogel compound 5 significantly reduced the IC50 values for HepG2, A549, MCF-7, and HCT-116 cells by 58.19%, 81.29%, 71.81%, and 67.16%, respectively. Furthermore, it lowered the IC50 values for VEGFR-2 and EGFRT790M by 29.66% and 68.18%, respectively.

PhysFiT: Physical-aware 3D Shape Understanding for Finishing Incomplete Assembly

Understanding the part composition and structure of 3D shapes is crucial for a wide range of 3D applications, including 3D part assembly and 3D assembly completion. Compared to 3D part assembly, 3D assembly completion is more complicated, which involves repairing broken or incomplete furniture that miss several parts with a toolkit. Given an incomplete assembly, 3D assembly completion seeks to identify its missing parts from multiple candidates, determine their poses, and produce complete assembly that is well-connected, structurally stable, and aesthetically pleasing. This task necessitates not only specialized knowledge of part composition but, more importantly, an awareness of physical constraints, i.e., connectivity, stability, and symmetry. Neglecting these constraints often results in assemblies that, although visually plausible, are impractical. To address this challenge, we propose PhysFiT, a physical-aware 3D shape understanding framework. This framework is built upon attention-based part relation modeling and incorporates connection modeling, simulation-free stability optimization and symmetric transformation consistency. We evaluate its efficacy on 3D part assembly and 3D assembly completion, a novel assembly task presented in this work. Extensive experiments demonstrate the effectiveness of PhysFiT in constructing geometrically sound and physically compliant assemblies.

Engaging Two Anions with Single Cation in Energetic Salts: Approach for Optimization of Oxygen Balance in Energetic Materials.

The field of high energy density materials faces a long-standing challenge to achieve an optimum balance between energy and stability. While energetic salt formation via a combination of oxygen- and nitrogen-rich anions (providing energy) with nitrogen-containing cations (providing stability) has been a proven approach for improving physical stability, constraints such as lowering density and energetic performance remain unresolved. This can be addressed by utilizing oxygen-containing cations for salt formation. However, this approach is rarely explored because its synthesis is challenging. In this work, we have designed an oxygen-rich cationic precursor 2 by incorporating 4-amino-3,5-dinitropyrazole with 3,4-diaminotriazole via an N-methylene-C bridge. Further combination with energetic acids resulted in the formation of high-performing, physically stable energetic salts 3-10. The salts were found to be generally more energetic than the salts of respective energetic acids with previously reported cations and showed prominent improvement in physical stability with respect to their anionic precursors. All the compounds were thoroughly characterized through IR, NMR spectroscopy, HRMS, and elemental analysis. Salt 9 was confirmed through 15N NMR analysis, and salts 2 and 8 were confirmed through single-crystal X-ray diffraction. Additional analyses such as Hirshfeld surface analysis, noncovalent interaction (NCI) analysis, and electrostatic potential studies were also carried out to correlate the structure-property relationship.

Enhanced delivery of rivastigmine for Alzheimer's disease: Convolvulus pluricaulis lipid hybrid nanoparticles

The study investigates the formulation and characterization of polymeric lipid hybrid nanoparticles (PLHNs) for targeted delivery of Rivastigmine and Convolvulus pluricaulis (C. pluricaulis, Shankhpushpi) extract to the brain. Employing a modified film hydration technique, PLHNs were optimized by adjusting lipid-to-polymer ratios, achieving nanoparticles with optimal size, zeta potential, and entrapment efficiency. The resulting nanoparticles, with sizes between approximately 150–225 nm, exhibited excellent physical stability and encapsulation efficiencies. Characterization through transmission electron microscopy (TEM) and scanning electron microscopy (SEM) confirmed their spherical and smooth morphology. Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) analyses showed no significant interactions between the drug, polymer, and plant extract, ensuring formulation stability. In vitro release studies demonstrated a controlled and sustained drug release, with the optimal formulation showing substantial release over 24 hours. The novel object recognition (NOR) test indicated enhanced cognitive function in animals treated with the optimal formulation, suggesting effective brain targeting and neuroprotective activity. Biochemical analyses supported these findings, revealing significant improvements in antioxidant enzyme levels and reductions in oxidative stress markers in treated animals. This study underscores the potential of PLHNs to enhance the delivery of neuroprotective agents, offering a promising strategy for treating neurodegenerative diseases.

Impact of storage temperature on physical stability and protein-lipid Co-oxidation in whey protein functional emulsions

The aim of this study was to investigate the effect of different storage temperatures (4 °C, 25 °C and 45 °C, denoted as T-4, T-25 and T-45, respectively) on the physical stability and protein-lipid co-oxidation of whey protein functional emulsions during the storage period at storage times of 1, 2, 3 and 6 months. At the 6th month of storage, samples stored at 45 °C were less physically stable than samples stored at 4 °C, as evidenced by an increase in particle size (5.50%), a decrease in zeta potential (7.93%), and a decrease in adsorbed protein concentration (36.8%). The most severe protein-lipid co-oxidation was induced in whey protein functional emulsions under 45 °C temperature conditions with increasing storage time. Protein oxidation products (carbonyls, N′-formyl-L-kynurenine, and sulfhydryl groups) and lipid oxidation products (lipid hydroperoxides, thiobarbituric acid reactive substances) were at their highest levels, and significant molecular changes were observed in the molecules of adsorbed protein or unadsorbed proteins. As the storage temperature rises it exposes the active sites such as internal sulfhydryl and hydrophobic groups in the protein, promoting cross-linking and aggregation. Cluster and correlation analyses showed that protein-lipid co-oxidation of emulsions inevitably occurs during storage, but low-temperature storage can delay this process. This study is of guiding significance for the quality maintenance of functional nutritional emulsions and the selection of storage conditions. In addition, this study may provide clearer solutions to the problems of whey protein denaturation and formation of lipid oxides caused by protein-lipid co-oxidation in the food industry, as well as to the problem of increasing the shelf life of products by choosing the appropriate storage, packaging, and transportation temperatures.

Surface-functionalized UIO-66-NH2 for dual-drug delivery of vancomycin and amikacin against vancomycin-resistant Staphylococcus aureus

BackgroundConventional antibacterial compounds can inhibit the growth of microorganisms, but their adverse effects and the development of drug limit their widespread use. The current study aimed to synthesize PEG-coated UIO-66-NH2 nanoparticles loaded with vancomycin and amikacin (VAN/AMK-UIO-66-NH2@PEG) and evaluate their antibacterial and anti-biofilm activities against vancomycin-resistant Staphylococcus aureus (VRSA) clinical isolates.MethodsThe VAN/AMK-UIO-66-NH2@PEG were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) to determine their size, polydispersity index (PDI), encapsulation efficiency (EE%), zeta-potential, drug release profile, and physical stability. Antibacterial activity was evaluated using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill assays. Biofilm formation by VRSA was assessed using the crystal violet (CV) and minimum biofilm eradication concentration (MBEC) assays. The effect of sub-MIC concentrations of the formulations on the expression of biofilm-related genes (icaA, icaD) and resistance-related genes (mecA, vanA) was investigated using quantitative real-time polymerase chain reaction (RT-qPCR).ResultsAs demonstrated by MIC, MBC and time-kill assay, the VAN/AMK-UIO-66-NH2@PEG nanoparticles exhibited enhanced antibacterial activity against VRSA isolates compared to free drugs and prepared formulations. Furthermore, CV and MBEC tests indicated that the VAN/AMK-UIO-66@NH2/PEG can reduce biofilm formation dramatically compared to VAN/AMK and VAN/AMK-UIO-66@NH2, due to its great drug release properties. This study also found that the expression level of the mecA, vanA, icaA, and icaD genes in VAN/AMK-UIO-66@NH2/PEG treated VRSA isolates was substantially decreased compared to other groups.ConclusionsThese findings highlighted the efficiency of VAN/AMK-UIO-66@NH2/PEG in combating antimicrobial resistance and biofilm formation in VRSA isolates. Future studies, particularly in vivo models, are necessary to evaluate the safety, efficacy, and clinical applicability of these nanoparticles for the treatment of bacterial infections.

FORMULATION AND IN VITRO TESTS OF KETOPROFEN NANOSUSPENSION USING THE MILLING METHOD WITH POLYMER VARIATIONS

Objective: The aim of this research was to formulate ketoprofen nanosuspension with a variety of polymers and to compare the dissolution rate of the nanosuspensions with ketoprofen suspension. Methods: Ketoprofen nanosuspension was formulated by milling method using a different polymer such as Polyvinyl Pyrrolidone (PVP) K-30 (F1), Polyvinyl Alcohol (PVA) (F2) and Hydroxy Propyl Methyl Cellulose (HPMC) (F3). Nanosuspensions were prepared and characterized, including organoleptic, pH, particle size, zeta potential, Polydispersity Index (PI), specific gravity, crystalline state determination, physical stability at room temperature for 3 mo, and in vitro dissolution test compared with ketoprofen suspension. Results: The ketoprofen nanosuspensions with PVP K-30 and PVA showed stable preparations, while those with HPMC showed less stability, as indicated by sedimentation during storage. The particle size values of PVP K-30 and PVA were 10.004±0.03 nm; and 9.560±0.01 nm; zeta potential and polydispersity index values met the test requirements. The dissolution rate of the ketoprofen nanosuspensions was higher with a cumulative of F1, F2, and F3 were 83.35%; 85.00%, and 81.09% after 60 min, while the ketoprofen suspension was only 7.62%. Conclusion: The milling method of ketoprofen nanosuspensions with PVP and PVA has more stable physical characteristics than nanosuspension with HPMC. The ketoprofen nanosuspensions have a higher dissolution rate than the ketoprofen suspension.

Self-assembled latanoprost loaded soluplus nanomicelles as an ophthalmic drug delivery system for the management of glaucoma

Glaucoma, a leading cause of blindness due to elevated intraocular pressure (IOP), is managed with medications like latanoprost (LAT), a prostaglandin analogue, to enhance aqueous outflow. Despite the challenge posed by eye anatomy and tear dynamics, effective ocular bioavailability via topical administration remains elusive. This study aims to optimize self-assembled nanomicelles incorporating LAT, an anti-glaucoma drug, belonging to BCS Class II (low solubility and high permeability) via a two-level, two-factor full factorial design, the nanomicelles were formulated via direct dissolution method and validated using design of expert. The optimized nanomicelles exhibited a spherical morphology, with a size of 69 nm and encapsulation efficiency of 77.5%, demonstrating a sustained LAT release over 12 h. In normotensive rabbits, the nanomicelles elicited a substantial reduction in intraocular pressure (IOP) by up to 40% for a duration of three days, that was significantly longer than the IOP-lowering efficacy of XALATAN eye drops (24 h). These findings indicated that self-assembled nanomicelles hold promise for enhancing the ocular bioavailability and extending the therapeutic duration of LAT, while providing the physical stability.

Bioactive Hybrids Containing Artificial Cell Membranes and Phyto-Gold-Silver Chloride Bio-Nanoparticles.

This research targets the need for eco-friendly strategies in the synthesis of bioactive materials, addressing the importance of valorization of vegetal waste. This study focuses on developing biohybrids containing biomimetic lipid vesicles and phytosynthesized gold-silver chloride nanoparticles (AuAgCl NPs) derived from Achillea millefolium L. extract. By leveraging the natural antioxidant and antimicrobial properties of the plant, the research proposes a sustainable approach to creating materials with potential biomedical applications. The biomimetic membranes were loaded with chlorophyll a, a natural spectral marker. Three types of bioactive materials (biohybrids) were developed by varying the lipid vesicle/AuAgCl NP ratio. Optical (UV-Vis, fluorescence emission, FTIR), structural (XRD), elemental (EDX, XPS), and morphological (TEM) studies were performed to characterize the bio-developed materials. The hydrophobic/hydrophilic characteristics of the samples were investigated by measuring the water contact angle, and their size was estimated by DLS and TEM. Zeta potential measurements were used to evaluate the physical stability of phyto-developed particles. Antioxidant properties of phyto-particles were investigated through the chemiluminescence technique. The obtained biomaterials exhibited high antioxidant activity and antiproliferative activity against HT-29 and B-16 cancer cells. Therapeutic index values were calculated for each biohybrid. Additionally, the bio-prepared hybrids revealed biocidal action against Staphylococcus aureus and Enterococcus faecalis. The phyto-developed biomaterials are promising in biomedical applications, particularly as adjuvants in cancer therapy.