Complete Solubilization Research Articles

Design and Biocompatibility of Biodegradable Poly(octamethylene suberate) Nanoparticles to Treat Skin Diseases.

Biodegradable aliphatic polyester formulations as carriers for topical drug delivery show the potential to encapsulate structurally different therapeutic compounds. Poly(octamethylene suberate) (POS) nanoparticles (POS-NPs) were used as a matrix to encapsulate four therapeutic molecules used to treat skin disorders: caffeine (CF), quercetin (QR), hydrocortisone (HC), and adapalene (AD). Hydrophobicity and chemical structure of bioactive compounds (BCs) influenced the physicochemical stability of drug-loaded nanoparticles. The particle size of drug-loaded nanoparticles was between 254.9 nm for the CF-POS-NP and 1291.3 for QR-POS-NP. Particles had a negative charge from -27.6 mV (QR) to -49.2 mV (HC). Drug loading content for all BC-POS-NPs varies between 36.11 ± 1.48% (CF-POS-NP) and 66.66 ± 4.87% (AD-POS-NP), and their entrapment efficiency is relatively high (28.30 ± 1.81% and 99.95 ± 0.04%, respectively). Calorimetric analysis showed the appearance of polymorphism for AD- and HC-loaded systems and the drug's complete solubilisation into all nanoparticle formulations. FTIR and NMR spectra showed apparent drug incorporation into the polymer matrix of NPs. The encapsulation of BCs enhanced the antioxidative effect. The prepared POS nanoparticles' cytotoxicity was studied using two dermal cell lines, keratinocyte (HaCaT) cells and fibroblasts (HDFn). The nanoparticle cytotoxic effect was more substantial on HaCaT cell lines. A reconstructed human epidermis (RHE) was successfully used to investigate the penetration of polymeric NPs. Based on permeation and histology studies, HC-POS-NPs and CF-POS-NPs were shown not to be suitable for dermal applications with the explored drug concentrations. AD presents a high permeation rate and no toxic impact on RHE.

Effect of hydroxylammonium chloride as a reductant for hydrochloric acid leaching of valuable metals from discarded lithium-ion batteries

The use of hydroxylammonium chloride as a reducing agent is proposed to enhance the acid leaching of cathode material from spent lithium-ion batteries. The current study was conducted using real waste from scooter batteries. The main metals found in this cathode material are Mn (43.6%), Li (4.2%), Ni (8.3%) and Co (2.6%), expressed as % w/w. The effect of the initial concentrations of the extracting agent (HCl) and the reducing agent (NH3OHCl) on the extraction yields of the target metals is investigated. The presence of NH3OHCl in HCl solutions exerts a highly effective influence during the initial 15 min of the leaching process, with a complete solubilization of Mn within that timeframe, in contrast to the 20% achieved in its absence. During that period, over 70% of Li is solubilized, while Ni and Co reach maximum solubilities of 7% and 5%, respectively. Extending the contact time to 24 h between the extracting solution and LIB waste enables nearly complete extraction of Ni and exceeds 60% for Co. An analysis of variance was used to identify significant factors to be included in multivariable regressions to predict extraction yields. These regressions are used to carry out a preliminary economic analysis of the leaching process based on gross profit. The optimum outcome is achieved when the extraction is conducted through two consecutive leaching processes. In the first process, 100% Mn and 75% of Li are recovered, while the second process recovers the remaining Li, 96% of Ni, and 60% of cobalt. Additionally, the stoichiometry of the reduction of manganese(IV) by NH3OHCl is studied through the correlation between the gas volume released during the leaching processes and the Mn solubilization reached. This reduction proceeds through two parallel reactions, resulting in the production of N2O and N2. The first of these reactions predominates, exhibiting an estimated selectivity of 87%.

A Thiourea Derivative of 2-[(1R)-1-Aminoethyl]phenol as a Chiral Sensor for the Determination of the Absolute Configuration of N-3,5-Dinitrobenzoyl Derivatives of Amino Acids.

In the exploration of chiral solvating agents (CSAs) for nuclear magnetic resonance (NMR) spectroscopy designed for the chiral analysis of amino acid derivatives, notable advancements have been made with thiourea-CSAs. 1-TU, derived from 2-[(1R)-1-aminoethyl]phenol and benzoyl isothiocyanate, is effective in the enantiodifferentiation of N-3,5-dinitrobenzoyl (N-DNB) amino acids. In order to broaden the application of 1-TU for configurational assignment, enantiomerically enriched N-DNB amino acids were analyzed via NMR. A robust correlation was established between the relative position of specific 1H and 13C NMR resonances of the enantiomers in the presence of 1-TU. 1,4-Diazabicyclo[2.2.2]octane (DABCO) was selected for the complete solubilization of amino acid substrates. Notably, the para and ortho protons of the N-DNB moiety displayed higher frequency shifts for the (R)-enantiomers as opposed to the (S)-enantiomers. This trend was consistently observed in the 13C NMR spectra for quaternary carbons bonded to NO2 groups. Conversely, an inverse correlation was noted for quaternary carbon resonances of the carboxyl moiety, amide carbonyl, and methine carbon at the chiral center. This observed trend aligns with the interaction mechanism previously reported for the same chiral auxiliary. The configurational correlation can be effectively exploited under conditions of high dilution or, significantly, under sub-stoichiometric conditions.

Direct elemental analysis of plant oils by inductively coupled plasma mass spectrometry: Simple sample dilution combined with oxygen introduction into the plasma

Assessment of trace metal concentrations in plant oils has been considered a crucial quality control marker for potential health risks, oil flavour, and oxidative stability. A straightforward inductively coupled plasma mass spectrometry (ICP-MS) methodology was developed and validated through introduction of argon:oxygen gas mixture into plasma, allowing for a direct elemental analysis of organic matrices. This approach offers the advantage of a simple one-step preparation of plant oil samples with negligible contamination risks. The complete solubilization of the oil matrix enables the determination of total metal content from a single test tube with low dilution factor of 5. The modified plasma conditions resulted in the development of a robust and accurate ICP-MS method providing limits of detection at sub ng·g−1 levels. The ICP-MS method allowed the determination of trace levels of Ba, Cd, Cu, Fe, Mn, Pb, Sn, V, and Zn in olive, sunflower and rapeseed oils.

Enhanced nutrient recovery from anaerobically digested poultry wastewater through struvite precipitation by organic acid pre-treatment and seeding in a bubble column electrolytic reactor

Limited mineralization of organic phosphorus to phosphate during the anaerobic digestion process poses a significant challenge in the development of cost-effective nutrient recovery strategies from anaerobically digested poultry wastewater (ADPW). This study investigated the influence of organic acids on phosphorus solubilization from ADPW, followed by its recycling in the form of struvite using a bubble column electrolytic reactor (BCER) without adding chemicals. The impact of seeding on the efficiency of PO43− and NH3-N recovery as well as the size distribution of recovered precipitates from the acid pre-treated ADPW was also evaluated. Pre-treatment of the ADPW with oxalic acid achieved complete solubilization of phosphorus, reaching ∼100% extraction efficiency at pH 2.5. The maximum removal efficiency of phosphate and ammonia-nitrogen from the ADPW were 88.9% and 90.1%, respectively, while the addition of 5 and 10 g/L struvite seed to the BCER increased PO43− removal efficiency by 9.6% and 11.5%, respectively. The value of the kinetic rate constant, k, increased from 0.0176 min−1 (unseeded) to 0.0198 min−1, 0.0307 min−1, and 0.0375 min−1 with the seed loading rate of 2, 5, and 10 g/L, respectively. Concurrently, the average particle size rose from 75.3 μm (unseeded) to 82.1 μm, 125.7 μm, and 148.9 μm, respectively. Results from XRD, FTIR, EDS, and dissolved chemical analysis revealed that the solid product obtained from the recovery process was a multi-nutrient fertilizer consisting of 94.7% struvite with negligible levels of heavy metals.

Nanoemulsion drug delivery system loaded with imiquimod: a QbD-based strategy for augmenting anti-cancer effects

BackgroundSkin cancer is becoming a public health concern due to increased exposure to environmental pollutants and UV rays, among other factors. In India, skin neoplasms constitute 2–3% of all human cancer cases, whereas in the USA, 2–3 million cases of non-melanoma skin cancer are reported annually. Various drugs are available in the market for treating skin cancer. Imiquimod (IMQ) is one such drug approved by the USFDA for managing basal cell malignancy, external genital warts, and actinic keratosis. The conventional dosage form of IMQ cream has several side effects that can lead to therapy interruption. Therefore, the present work aims to develop an IMQ nanoemulsion with improved solubility, in vitro drug release and stability. Nanoemulsion was formulated using oleic acid/rose oil, with polysorbate 20/propylene glycol selected as the oil phase and Smix, respectively. Optimization carried out using a 32 factorial design with the aid of a quadratic model. Characterization was conducted for parameters, namely viscosity, pH, drug content, globule size, zeta potential and entrapment efficiency. Thermodynamic stability studies were conducted to assess the stability of the formulation. Furthermore, the optimized system was subjected to TEM analysis, in vitro drug release and in vitro cytotoxicity assay (MTT assay).ResultsNanoemulsions were found to be in the size range of 152.80–470.13 nm and exhibited a spherical shape. Zeta potential values ranged from − 28.93 to − 58.48 mV. DSC measurements indicated the complete solubilization of IMQ in the nanoemulsion system. The optimized formulation F1 displayed the following characteristics: a globule size < 200 nm, a zeta potential > − 55 mV, a polydispersity index < 0.2, % drug content of 102.89 ± 1.06, % entrapment efficiency of 97.59 ± 0.24, a pH of 4.77 ± 0.06, and a viscosity of 4.06 ± 0.06 poise. In vitro IMQ release studies of nanoemulsion and commercial cream showed approximately 70% and 34% drug release, respectively, at the end of 8 h. Moreover, the in vitro cytotoxicity assay depicted that F1 exhibited greater cytotoxic potential compared to the commercial formulation against the A431 cell line.ConclusionThe present investigation showed a significant improvement in in vitro drug release of the BCS class IV drug IMQ and enhanced cytotoxic activity against cancerous cells. IMQ-loaded nanoemulsion represents a promising vehicle for delivering treatment to the skin for treating skin cancer.Graphical abstract

Monitoring galactolipid digestion and simultaneous changes in lipid-bile salt micellar organization by real-time NMR spectroscopy

The use of Nuclear Magnetic Resonance spectroscopy for studying lipid digestion in vitro most often consists of quantifying lipolysis products after they have been extracted from the reaction medium using organic solvents. However, the current sensitivity level of NMR spectrometers makes possible to avoid the extraction step and continuously quantify the lipids directly in the reaction medium. We used real-time 1H NMR spectroscopy and guinea pig pancreatic lipase-related protein 2 (GPLRP2) as biocatalyst to monitor in situ the lipolysis of monogalactosyl diacylglycerol (MGDG) in the form of mixed micelles with the bile salt sodium taurodeoxycholate (NaTDC). Residual substrate and lipolysis products (monogalactosyl monoacylglycerol (MGMG); monogalactosylglycerol (MGG) and octanoic acid (OA) were simultaneously quantified throughout the reaction thanks to specific proton resonances. Lipolysis was complete with the release of all MGDG fatty acids. These results were confirmed by thin layer chromatography (TLC) and densitometry after lipid extraction at different reaction times. Using diffusion-ordered NMR spectroscopy (DOSY), we could also estimate the diffusion coefficients of all the reaction compounds and deduce the hydrodynamic radius of the lipid aggregates in which they were present. It was shown that MGDG-NaTDC mixed micelles with an initial hydrodynamic radius rH of 7.3 ± 0.5 nm were changed into smaller micelles of NaTDC-MGDG-MGMG of 2.3 ± 0.5 nm in the course of the lipolysis reaction, and finally into NaTDC-OA mixed micelles (rH of 2.9 ± 0.5 nm) and water soluble MGG. These results provide a better understanding of the digestion of galactolipids by PLRP2, a process that leads to the complete micellar solubilisation of their fatty acids and renders their intestinal absorption possible.

Advanced biomaterial agent from chitosan/poloxamer 407-based thermosensitive hydrogen containing biosynthesized silver nanoparticles using Eucalyptus camaldulensis leaf extract.

The emergence of multidrug-resistant (MDR) pathogens poses a significant challenge for global public health systems, increasing hospital morbidity and mortality and prolonged hospitalization. We evaluated the antimicrobial activity of a thermosensitive hydrogel containing bio-synthesized silver nanoparticles (bio-AgNPs) based on chitosan/poloxamer 407 using a leaf extract of Eucalyptus calmadulensis. The thermosensitive hydrogel was prepared by a cold method after mixing the ingredients and left at 4°C overnight to ensure the complete solubilization of poloxamer 407. The stability of the hydrogel formulation was evaluated at room temperature for 3 months, and the absorption peak (420 nm) of the NPs remained unchanged. The hydrogel formulation demonstrated rapid gelation under physiological conditions, excellent water retention (85%), and broad-spectrum antimicrobial activity against MDR clinical isolates and ATCC strains. In this regard, minimum inhibitory concentration and minimum microbial concentration values of the bio-AgNPs ranged from 2-8 μg/mL to 8-128 μg/mL, respectively. Formulation at concentrations <64 μg/mL showed no cytotoxic effect on human-derived macrophages (THP-1 cells) with no induction of inflammation. The formulated hydrogel could be used in biomedical applications as it possesses a broad antimicrobial spectrum and anti-inflammatory properties without toxic effects on human cells.

Tethered Bilayer Lipid Membrane Platform for Screening Triton X-100 Detergent Replacements by Electrochemical Impedance Spectroscopy.

In light of regulatory considerations, there are ongoing efforts to identify Triton X-100 (TX-100) detergent alternatives for use in the biological manufacturing industry to mitigate membrane-enveloped pathogen contamination. Until now, the efficacy of antimicrobial detergent candidates to replace TX-100 has been tested regarding pathogen inhibition in endpoint biological assays or probing lipid membrane disruption in real-time biophysical testing platforms. The latter approach has proven especially useful to test compound potency and mechanism of action, however, existing analytical approaches have been limited to studying indirect effects of lipid membrane disruption such as membrane morphological changes. A direct readout of lipid membrane disruption by TX-100 detergent alternatives would be more practical to obtain biologically relevant information to guide compound discovery and optimization. Herein, we report the use of electrochemical impedance spectroscopy (EIS) to investigate how TX-100 and selected replacement candidates-Simulsol SL 11W (Simulsol) and cetyltrimethyl ammonium bromide (CTAB)-affect the ionic permeability of tethered bilayer lipid membrane (tBLM) platforms. The EIS results revealed that all three detergents exhibited dose-dependent effects mainly above their respective critical micelle concentration (CMC) values while displaying distinct membrane-disruptive behaviors. TX-100 caused irreversible membrane disruption leading to complete solubilization, whereas Simulsol caused reversible membrane disruption and CTAB induced irreversible, partial membrane defect formation. These findings establish that the EIS technique is useful for screening the membrane-disruptive behaviors of TX-100 detergent alternatives with multiplex formatting possibilities, rapid response, and quantitative readouts relevant to antimicrobial functions.

Structural Insights into Polymer-Bounded Lipid Nanodiscs.

Membrane proteins are an essential part of signaling and transport processes and are targeted by multiple drugs. To isolate and investigate them in their native state, polymer-bounded nanodiscs have become valuable tools. In this study, we investigate the lipid model system dimyristoyl-phosphocholine (DMPC) with the nanodisc-forming copolymers styrene maleic acid (SMA) and diisobutylene maleic acid (DIBMA). Using small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS), we studied the influence of polymer concentration and temperature on the nanodisc structure. In Tris buffer, the size of nanodiscs formed with SMA is smaller compared to DIBMA at the same polymer ratio. In both cases, the size decreases monotonically with increasing polymer concentration, and this effect is more pronounced when using SMA. Measurements at temperatures (T) between 5 and 30 °C in phosphate buffer showed an incomplete solubilization at high T even at polymer/lipid ratios above that required for complete lipid solubilization. For DIBMA, the nanodiscs developed at lower temperatures are stable and the net repulsion increases, while for SMA, the individual nanodiscs possess smaller sizes and are less affected by T. However, using DLS, one can observe SMA agglomerates at low T. Interestingly, for both polymers, no drastic changes of the observable parameters (radius and bilayer thickness) are seen upon cooling, which would indicate a sharp (first-order) phase transition from liquid-crystalline to gel, but only gradual changes. Hence, we conclude that the transition from a gel toward a liquid-crystalline lipid phase proceeds over a broad T-range compared to a continuous lipid bilayer. These results can pave the way toward the development of better protocols for studying membrane proteins stabilized in this type of membrane mimics.

Development and characterization of different dosage forms of nifedipine/indomethacin fixed-dose combinations

Studies have shown that 40 individuals out of 100,000 are diagnosed with rheumatoid arthritis (RA) yearly, with a total of 1.3 million in the United States. Furthermore, the impact of RA in some cases can extend to cardiovascular diseases (CVD), as the studies showed that 84% of RA patients are at risk of developing hypertension. This study aims to design and develop different dosage forms (capsule-in-capsule and three-dimensional (3D) printed tablet) of nifedipine/indomethacin fixed-dose combination (FDC). The hot-melt extrusion (HME) was utilized alone and with fused deposition modeling (FDM) techniques The developed dosage forms were intended to provide delayed-extended and immediate release profiles for indomethacin and nifedipine, respectively. FDC dosage forms were successfully developed and characterized. Nifedipine formulations showed significant improvement in release profiles, having 94% of the drug release at 30 min compared with pure nifedipine, which had a percent release of 2%. Furthermore, the release of indomethacin was successfully delayed at a pH of 1.2 and extended at a pH of 6.8. Differential scanning calorimetry results showed endothermic crystalline peaks at 165 °C and 176 °C for indomethacin and nifedipine, respectively. Moreover, the thermal analysis of all formulations showed the absence of the endothermic peaks indicating complete solubilization of indomethacin and nifedipine in the polymeric carriers. All formulations had post-processing drug content in the range of 95%–98%. Moreover, results from the stability study showed that all formulations were able to remain chemically and physically stable with no signs of recrystallization or degradation. The designed FDC dosage forms could improve the quality of life by enhancing patient compliance and preventing the need for polypharmacy.

Mix-and-Match Diols: Adjusting Self-Assembly of Micellar Phases in Choline Chloride Eutectics

The common Deep Eutectic Solvent (DES) ‘ethaline’ (1:2 choline chloride:ethylene glycol) was examined here as a basis for the self-assembly of the surfactant dodecyltrimethylammonium bromide (C12TAB). A phase diagram was constructed, showing evidence for a L1 (micellar) phase, confirmed by tensiometry to have a room temperature critical micelle concentration (CMC) of 1.2 wt.%. Small angle neutron scattering (SANS) measurements indicate formation of interacting globular micelles with slightly smaller apparent radii than in water. The apparent mesophase/multiphase region was studied using SWAXS, demonstrating rich mesoscopic lyotropic liquid crystalline phase behaviour, with evidence for lamellar Lα peaks, alongside potential co-crystalline phases. We attempted to tailor the self-assembly by studying binary DES containing longer diols including 1,2-propanediol, 1,3-propanediol, 1,4-butanediol, and 1,5-pentanediol, and ternary DES where the HBD component was a 1:1 ethylene glycol:diol mixture. However, synchrotron SAXS showed that only ternary ‘propethaline’ mixtures displayed signs of self-assembly and micellization, perhaps due to the reduction in calculated Gordon parameter, which decreases linearly with increasing alkyl chain length. Systematic differences were thus observed in the ability of the solvents to modulate assembly, from globular micelles in ChCl:EG, to weaker assembly in long-tail DES, and complete solubilisation in butaline and pentaline.

Detergent-Assisted Protein Digestion-On the Way to Avoid the Key Bottleneck of Shotgun Bottom-Up Proteomics.

Gel-free bottom-up shotgun proteomics is the principal methodological platform for the state-of-the-art proteome research. This methodology assumes quantitative isolation of the total protein fraction from a complex biological sample, its limited proteolysis with site-specific proteases, analysis of the resulted peptides with nanoscaled reversed-phase high-performance liquid chromatography-(tandem) mass spectrometry (nanoRP-HPLC-MS and MS/MS), protein identification by sequence database search and peptide-based quantitative analysis. The most critical steps of this workflow are protein reconstitution and digestion; therefore, detergents and chaotropic agents are strongly mandatory to ensure complete solubilization of complex protein isolates and to achieve accessibility of all protease cleavage sites. However, detergents are incompatible with both RP separation and electrospray ionization (ESI). Therefore, to make LC-MS analysis possible, several strategies were implemented in the shotgun proteomics workflow. These techniques rely either on enzymatic digestion in centrifugal filters with subsequent evacuation of the detergent, or employment of MS-compatible surfactants, which can be degraded upon the digestion. In this review we comprehensively address all currently available strategies for the detergent-assisted proteolysis in respect of their relative efficiency when applied to different biological matrices. We critically discuss the current progress and the further perspectives of these technologies in the context of its advances and gaps.

Thermofluor-Based Optimization Strategy for the Stabilization of Recombinant Human Soluble Catechol-O-Methyltransferase

Catechol-O-methyltransferase (COMT) has been involved in a number of medical conditions including catechol-estrogen-induced cancers and a great range of cardiovascular and neurodegenerative diseases such as Parkinson’s disease. Currently, Parkinson’s disease treatment relies on a triple prophylaxis, involving dopamine replacement by levodopa, the use of aromatic L-amino acid decarboxylase inhibitors, and the use of COMT inhibitors. Typically, COMT is highly thermolabile, and its soluble isoform (SCOMT) loses biological activity within a short time span preventing further structural and functional trials. Herein, we characterized the thermal stability profile of lysate cells from Komagataella pastoris containing human recombinant SCOMT (hSCOMT) and enzyme-purified fractions (by Immobilized Metal Affinity Chromatography—IMAC) upon interaction with several buffers and additives by Thermal Shift Assay (TSA) and a biological activity assessment. Based on the obtained results, potential conditions able to increase the thermal stability of hSCOMT have been found through the analysis of melting temperature (Tm) variations. Moreover, the use of the ionic liquid 1-butyl-3-methylimidazolium chloride [C4mim]Cl (along with cysteine, trehalose, and glycerol) ensures complete protein solubilization as well as an increment in the protein Tm of approximately 10 °C. Thus, the developed formulation enhances hSCOMT stability with an increment in the percentage of activity recovery of 200% and 70% when the protein was stored at 4 °C and −80 °C, respectively, for 12 h. The formation of metanephrine over time confirmed that the enzyme showed twice the productivity in the presence of the additive. These outstanding achievements might pave the way for the development of future hSCOMT structural and biophysical studies, which are fundamental for the design of novel therapeutic molecules.

High pressure phase behavior of ternary system (carbon dioxide + globalide + dichloromethane) at different dichloromethane to globalide mass ratios

Globalide is a 16-membered macrolactone, which contains a double bond, typically used in the fragrance industry, due to its musky odor. However, its application as a monomer for the synthesis of the polyester polyglobalide (PGl) is drawing attention of the scientific community, due to its biocompatible and non-toxic character, being a great candidate for biomedical applications. This kind of polymer are frequently synthesized using green solvents, and pressurized carbon dioxide is being reported as a suitable alternative in polymerization processes. In this work, we evaluate the phase behavior of the ternary system carbon dioxide (1) + globalide (2) + dichloromethane (3), at high pressures. Experimental measurements of the phase equilibrium of the system were carried out at the following dichloromethane/globalide mass ratios: 0.5:1, 1:1 and 2:1, in a range of temperatures varying from 313 to 343 K. Thermodynamic modeling of the experimental data was performed using Peng Robinson equation of state with van der Waals biparametric quadratic mixing rule (PR-vdW2). Phase transitions of vapor–liquid (bubble point), liquid–liquid and vapor–liquid–liquid types were observed. The system showed LCST behavior (Lower Critical Solution Temperature), whose temperature increase results in higher pressures necessary for complete solubilization of the system. Dichloromethane showed to be an effective co-solvent, reducing the pressure required for the solubilization of the system. PR-vdW2 equation satisfactorily represented the system, with acceptable deviations under the studied conditions.

Docetaxel-loaded borage seed oil nanoemulsion with improved antitumor activity for solid tumor treatment: Formulation development, in vitro, in silico and in vivo evaluation

In the present work, docetaxel-nanoemulsion (DTX-NE) was developed with the aim to improve its therapeutic activity while reducing the side-effects by targeted delivery approach. The unique approach about the developed formulation was use of borage seed oil as the oil phase which has abundant gamma-linolenic acid (GLA) in it and has been previously reported for its anticancer activity. DTX was solubilized in Borage oil and the system was emulsified using Phospholipid (Lipoid E−80). The nanoemulsion was developed by high shear homogenization and ultrasonication. Systematic optimization of critical factors was carried out using Box-Behnken design. The optimized nanoemulsion showed particle size (180.2 ± 4.5 nm), zeta potential (−33.7 ± 1.9 mV) and PDI (0.178 ± 0.01) within the desired limits. The drug entrapment efficiency was found to be 96.41 ± 4.7% while drug loading was found to be 12.87 ± 1.3%. Further, FTIR, DSC and XRD analysis revealed compatibility of the drug with the excipients in addition to complete drug solubilization and entrapment. Further, in vitro release study performed in PBS (pH 7.4) indicated a biphasic profile while release kinetic evaluation showed best fitting as per Korsemeyer-Peppas model with drug release through Fickian diffusion mechanism. In silico docking performed of DTX and GLA suggested excellent binding with microtubule subunit with the binding affinity of −6.4 kcal/mol and −5.7 kcal/mol, respectively. In vivo pharmacokinetic studies in Albino Wistar rats indicated significant improvement in AUC (3.9-folds), t1/2 (2.0-folds) and MRT (4.0-folds) from DTX-NE vis-à-vis the plain drug, respectively. Furthermore, antitumor efficacy of DTX-NE showed significant reduction in the tumor growth (3.17-times) than the free drug and marketed formulation (Taxotere®).

Cardinal acuity on the extraction and characterization of soluble collagen from the underutilized abattoir junks for clinical demands

Improper utilization of solid wastes causes environmental flusters by prying the live organisms in the form of abattoir scraps. One of the most common underutilized biowastes in slaughter houses are bovine Achilles Tendons (AT). It has the rich source of type I collagen, since AT is composed of stiff and rigid materials, the collagen yield in the solubilized form is almost non pragmatic with conservative methods. Herein, this work emphasis the state-of-art on the design of seamless technique for the extraction of collagenous proteins with complete solubilization for clinical and healthcare application. High yield of soluble collagen (72%) was obtained through pepsin digestion coupled ultrasonic wave method. The triple helical structure of the native soluble type I collagen was confirmed through electrophoresis, circular dichroism (CD) and vibrational circular dichroism (VCD) analysis. The scanning electron microscopy (SEM) depicts the highly interconnected microfibrillar porous structure of the collagen as scaffold. The in vitro biocompatibility and fluorescent activity on NIH 3T3 fibroblast cells over the microfibrillar collagen scaffold possess excellent cell viability and proliferation at different time. Thus, it can be concluded that the AT-Collagen could be promising value-added bloom to bioeconomic growth for healthcare industries.

Surfactant-Mediated Solubilization of Myelin Figures: A Multistep Morphological Cascade.

Lamellar mesophases of insoluble lipids are readily solubilized by the micellar mesophases of soluble surfactants. This simple process underscores a broad array of biochemical methodologies, including purification, reconstitution, and crystallization of membrane proteins, as well as the isolation of detergent-resistant membrane fractions. Although much is now known about the thermodynamic driving forces of membrane solubilization, the kinetic pathways by which the surfactant alters vesicular mesophases are only beginning to be appreciated. Little is known about how these interactions affect the solubilization of more complex, multilamellar mesophases. Here, we investigate how a common zwitterionic detergent affects the solubilization of a smectic, multilamellar, cylindrical mesophase of lipids, called the myelin figure. Our results reveal that myelin solubilization occurs in a multistep manner, producing a well-defined sequence of morphologically distinct intermediates en route to complete solubilization. The kinetic processes producing these intermediates include (1) coiling, which encompasses the formation, propagation, and tightening of extended helices; (2) thinning, which reflects the unbinding of lamellae in the smectic stacks; and (3) detachment or retraction, which either dissociates the myelinic protrusion from the source lipid mass or returns the myelinic protrusion to the source lipid mass─all in transit toward complete solubilization. These occasionally overlapping steps are most pronounced in single-lipid component myelins, while compositionally graded multicomponent myelins inhibit the coiling step and detach more frequently. Taken together, the appearance of these intermediates during the solubilization of myelins suggests a complex free-energy landscape characterizing myelin solubilization populated by metastable, morphological intermediates correlated with locally minimized changes in energy dependent upon the mesophase's composition. This then predicts the accessibility of structurally distinct, kinetic intermediates─such as loose and tight coiled helices, peeled myelins, retracted tubes, and detached protrusions─before reaching the stable ground state corresponding to a dissolved suspension of mixed surfactant-lipid micelles.

Formulation development of loratadine immediate- release tablets using hot-melt extrusion and 3D printing technology

The main goal of this study was to develop immediate release Fused Deposition Modeling (FDM) 3D printed loratadine tablets using hot-melt extrusion (HME) filaments. Loratadine was used as a model drug with 10% (w/w) drug loading. Ten different formulations were prepared using Crospovidone and croscarmellose as super-disintegrants, mannitol as a pore-forming agent, and polyethylene oxide-N80 and hydroxypropyl cellulose-EF as polymeric carriers. A three-point bend test was performed to determine the filaments' elasticity, strength, and stiffness in order to evaluate the filaments printability. The printable filaments were then printed using an (Prusa i3 MK3S) FDM-3D printer in a grid pattern and with (40–60%) infill to accelerate the drug release. The physical mixtures, filaments, and 3D printed tablets were analyzed using differential scanning calorimetry (DSC). Fourier transform infrared spectroscopy (FTIR) was performed to investigate the interactions between loratadine and polymeric carriers. The in-vitro drug release profile of the printed tablets was tested. Based on the filament's mechanical properties, six filaments were printable. The DSC thermograms indicated complete solubilization of loratadine in the polymeric carrier. All printed tablets exhibited a drug release of (86.1–96.9%) in 30 min. HME showed great potential to develop immediate release filaments which were suitable for FDM-3D printing.

A Sebum-Mimetic Lipid Monolayer and Its Interaction with (Bio)Surfactants

Surfactants present in cleansing formulations interact not only with the unwanted lipids accumulating on the human skin (dirt) but also with its protective lipidic layer (sebum). Development of simple models of human sebum would help to compare different surfactants and biosurfactants under the same conditions. In this contribution we propose a first monolayer model of synthetic sebum composed of lard, stearic acid, lanolin, squalane and cholesterol. The monolayer compression isotherm features a gas-liquid (G-LE1), two liquid-liquid transitions (LE1-LE2 and LE2-LC), and a collapse at πcoll = 45 mN/m. The monolayer spread on pure water and pre-compressed to π0 = 30 mN/m was exposed to four synthetic surfactants (sodium lauryl sulfate (SLS), sodium laureth sulfate (SLES), ammonium lauryl sulfate (ALS) and cocamidopropyl betaine (CAPB)) and four plant extracts (oat (Avena sativa L.), horse chestnut (Aesculus hippocastanum L.), cowherb (Vaccaria hispanica [P. Mill.] Rauschert), soybean (Glycine max L.) and soapwort (Saponaria officinalis L.)) introduced to the subphase at a dry mass content of 1% (w/w). Three modes of the monolayer-(bio)surfactant interactions were observed: (1) complete solubilization (SLS, SLES, ALS, CAPB); (2) penetration accompanied by an increase of surface pressure and elasticity but without solubilization (horse chestnut, cowherb, soapwort); (3) no interaction (oat, soybean).