Narrow Polydispersity Index Research Articles

Capsicum annuum Oleoresin Nanoemulgel - Design Characterization and In vitro Investigation of Anticancer and Antimicrobial Activities.

The use of naturally occurring bioactive materials is getting great attention owing to their safety and environmental properties. Oily compounds, known as oleoresins, are expected to provide an important source for the natural products industry aiming to develop novel treatments for skin conditions. In this work, Capsicum annuum oleoresin nanoemulgel formulations have been prepared and investigated for their antibacterial and anticancer properties. Several C. annuum oleoresin nanoemulgel formulations were prepared by incorporating a Carbopol 940 gel in a self-nanoemulsifying nanoemulsion consisting of C. annuum, tween 80, and span 80. The systems were characterized for particle size, polydispersity index (PDI), zeta potential, and rheology. The in vitro antimicrobial and cytotoxic activities of the optimum formulation were evaluated. The selected formulation is composed of 40% tween, 10% span 80, and 40% C. annuum oleoresin. This formulation produced a stable nanoemulsion with a narrow PDI value of 0.179 ± 0.08 and a droplet size of 104.0 ± 2.6 nm. Results of the in vitro antimicrobial studies indicated high potency of the systems against methicillin-resistant Staphylococcus aureus (MRSA) (zone of inhibition of 29 ± 1.9 mm), E. coli (33 ± 0.9 mm), K. pneumonia (30 ± 1.4 mm), and C. albicans (21 ± 1.5 mm), as compared to the reference antibiotic, ampicillin (18 ± 1.4 mm against K. pneumonia), and antifungal agent, fluconazole (12 ± 0.1 mm against C. albicans). Furthermore, cytotoxicity results, expressed as IC50 values, revealed that the oleoresin and its nanoemulgel had the best effects against the HepG2 cell line (IC50 value of 79.43 μg/mL for the nanoemulgel) and MCF7 (IC50 value of 57.54 μg/mL), and the most potent effect was found against 3T3 (IC50 value of 45.7 μg/m- L). On the other side, the system did not substantially exhibit activity against By-61 and Hela. C. annuum oleoresin and its nanoemulgel can be considered valuable sources for the discovery of new antibacterial, antifungal, and anticancer compounds in the pharmaceutical industry, especially due to their potent activity against various cancer cell lines as well as bacterial and fungal strains.

Establishment and inactivation of mono-species biofilm in a semipilot-scale water distribution system using nanocomposite of silver nanoparticles/montmorillonite loaded cationic chitosan

This study presents a novel approach in the synthesis and characterization of nanocomposites comprising cationic chitosan (CCS) blended with varying concentrations of silver nanoparticles/montmorillonite (AgNPs/MMT). AgNPs/MMT was synthesized using soluble starch as a reducing and stabilizing agent. Subsequently, nanocomposites, namely CCS/AgMMT-0, CCS/AgMMT-0.5, CCS/AgMMT-1.5, and CCS/AgMMT-2.5, were developed by blending 2.5 g of CCS with 0, 0.5, 1.5, and 2.5 g of AgNPs/MMT, respectively, and the corresponding nanocomposites were prepared using ball milling technique. Transmission electron microscopy (TEM) analysis revealed the formation of nanocomposites that exhibiting nearly spherical morphologies. Dynamic light scattering (DLS) measurements displayed average particle sizes of 1183 nm, 131 nm, 140 nm, and 188 nm for CCS/AgMMT-0, CCS/AgMMT-0.5, CCS/AgMMT-1.5, and CCS/AgMMT-2.5, respectively. The narrow polydispersity index (~0.5) indicated uniform particle size distributions across the nanocomposites, affirming monodispersity. Moreover, the zeta potential values exceeding 30 mV across all nanocomposites that confirmed their stability against agglomeration. Notably, CCS/AgMMT-2.5 nanocomposite exhibited potent antibacterial and antibiofilm properties against diverse pipeline materials. Findings showed that after 15 days of incubation, the highest populations of biofilm cells, Pseudomonas aeruginosa biofilm, developed over UPVC, MDPE, DCI, and SS, with corresponding HPCs of 4.79, 6.38, 8.81, and 7.24 CFU/cm2. The highest cell densities of Enterococcus faecalis biofilm in the identical situation were 4.19, 5.89, 8.12, and 6.9 CFU/cm2. The nanocomposite CCS/AgMMT-2.5 exhibited the largest measured zone of inhibition (ZOI) against both P. aeruginosa and E. faecalis, with measured ZOI values of 19 ± 0.65 and 17 ± 0.21 mm, respectively. Remarkably, the research indicates that the youngest biofilm exhibited the most notable rate of inactivation when exposed to a dose of 150 mg/L, in comparison to the mature biofilm. These such informative findings could offer valuable insights into the development of effective antibiofilm agents and materials applicable in diverse sectors such as water treatment facilities, medical devices, and industrial pipelines.

Highly efficient CO2 and propylene oxide co-polymerization using Zn glutarate/Zn-Cr double metal cyanide composite catalyst

A highly active zinc glutarate-double metal cyanide (DMC) composite catalyst (ZnGA/Zn-CrDMC) was designed for the carbon dioxide (CO2) and propylene oxide (PO) copolymerization reaction. The composite catalyst was synthesized in a rheological phase reaction and characterized using Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The synthesized composite catalysed the solvent free reactions of PO and CO2 to afford biodegradable polypropylene carbonate (PPC) copolymer. 1H NMR,13C NMR, FT-IR and ESI-TOF mass spectrometry measurements were employed to confirm the characteristics of the PPC produced. Under optimal reaction conditions (50 bar CO2, 70 °C, 24 h), the ZnGA-Zn3[Cr(CN)6]2 composite displayed higher catalytic activities in the copolymerization reactions than the individual catalysts. The ZnGA:Zn3[Cr(CN)6]2 ratio of 15:1 gave PPC yield of 47.9 g polymer/g cat compared to ZnGA that produced 42.6 g polymer/ g cat in 24 h. In addition, the PPC produced from the composite catalyst displayed higher carbonate linkage content (Fc = 85.4 %) compared to the value of Fc = 33.9 %. obtained using the Zn3[Cr(CN)6]2 catalyst. Similaly, the composite catalsyt produced PPC with molecular weight of 4200 g/mol and narrow polydispersity index of 2.2. The resultant PPC copolymer displayed good thermal stability, exhibiting a high degradation temperatures (TGA-10%) of 229 °C and complete decomposition at 350 °C.

TPGS-PLA nanomicelles for targeting lung cancer; synthesis, characterization, and in vitro antitumor efficacy

Combination therapy is a significant approach to enhance antitumor efficacy. Several mechanisms like tumor progression and neo angiogenesis can be targeted together via combination therapy to achieve successful anticancer effect. The proposed study involves preparation and optimization of antitumor drugs Palbociclib (PAL) and Regorafenib (REG) encapsulated in d-α-Tocopheryl Polyethylene Glycol Succinate (TPGS) Poly lactic acid (PLA) nanomicelles to treat lung cancer. TPGS-PLA nanomicelles were fabricated with thin film hydration method. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and 1H nuclear magnetic resonance (1HNMR) was performed to confirm polymerization of TPGS-PLA. PAL and REG loaded TPGS-PLA nanomicelles (PAL-REG-TPGS-PLAM) components were optimized using Box Behnken design. Particle size (PS), polydispersity index (PDI) and zeta potential (ZP) were evaluated using zetasizer followed by investigating the morphology of nanomicelles via scanning electron microscopy (SEM). Moreover, in vitro release of PAL-REG-TPGS-PLAM was investigated and compared with PAL dispersion, REG dispersion, PAL-REG dispersion and monotherapies, i.e. PAL-TPGS-PLAM and REG-TPGS-PLAM. Our results demonstrated the PS of all the tested formulations in the range of 120–190 nm, with narrow PDI of 0.2–0.3 and ZP of −18 to −30 mV. SEM analysis exhibited spherical shaped nanomicelles with uniform distribution. Polymerization of the TPGS-PLA was confirmed by the FTIR, 1HNMR and DSC. In-vitro drug release profiles of PAL-REG-TPGS-PLAM and the monotherapies of PAL-TPGS-PLAM and REG-TPGS-PLAM showed significantly sustained pattern of the drug release when compared with pure drug dispersions of PAL and REG. In-vitro cell lines studies showed significantly reduced cell viability (p < 0.05) in H69PR cells, when treated with PAL-TPGS-PLAM, REG-TPGS-PLAM and PAL-REG-TPGS-PLAM as compared to blank TPGS-PLAM and respective drug dispersion. However, PAL-REG-TPGS-PLAM demonstrated more significant (p < 0.01) antitumor results then the former groups. It can be concluded that PAL-REG-TPGS-PLAM is capable of improved antitumor effect of PAL and REG, most probably due to their synergistic effects and targeted drug delivery.

Flexible Polyurethane Foams from Bio-Based Polyols: Prepolymer Synthesis and Characterization.

Bio-polyols (BPOs), characterized by a hydroxyl number up to around 90 mg KOH/g, narrow polydispersity index and relatively low molecular mass up to 2000 g/mol, were synthetized from partially and completely epoxidized soybean and linseed oils and caprylic acid or 3-phenyl butyric acid. These BPOs were used in the presence of toluene diisocyanate to produce polyurethane (PU) foams by using a quasi-prepolymer method involving a two-step reaction. A detailed structural investigation of the prepolymers from toluene diisocyanate and both BPOs and polypropylene glycol was conducted by SEC and solution NMR. The apparent density of the foams was in the range of 40-90 kg/m3, with higher values for foams from the aromatic acid. All the foams showed an open-cell structure with uniform and regular shape and uniform size. The specific Young's moduli and compression deflection values suggest superior mechanical properties than the reference foams. The novel synthesized polyurethanes are excellent candidates to partially replace petroleum-based materials.

Organic carbonates as green and sustainable complexing agents for double metal cyanide catalysts for the synthesis of polyether and poly(ether-carbonate) polyols

We investigated various linear carbonates, including dimethyl carbonate and diethyl carbonate, and cyclic carbonates such as ethylene carbonate, propylene carbonate (PC), butylene carbonate, and glycerol carbonate, as complexing agents (CAs) for the preparation of double metal cyanide (DMC) catalysts. The DMC catalysts bearing carbonate complexing agents exhibited good to excellent activities for the ring-opening polymerization of epoxides (turnover frequencies of up to 467 min−1) and the copolymerization of epoxides and CO2, producing polyether polyols with moderate molecular weights (1700–9700 g mol−1), narrow polydispersity indexes (1.1–1.2), very low unsaturation values (0.002–0.009), and low viscosities (438 −997 cP). The DMC catalyst bearing PC also afforded linear and branched polycarbonate polyols in high yields (up to 83%) and carbonate contents (up to 36 mol%). Density functional theory calculations were also performed to understand the effect of the CAs on the structural properties and activities of the corresponding DMC catalysts.

Dendrimers as Nanocarriers for the Delivery of Drugs Obtained from Natural Products.

Natural products have proven their value as drugs that can be therapeutically beneficial in the treatment of various diseases. However, most natural products have low solubility and poor bioavailability, which pose significant challenges. To solve these issues, several drug nanocarriers have been developed. Among these methods, dendrimers have emerged as vectors for natural products due to their superior advantages, such as a controlled molecular structure, narrow polydispersity index, and the availability of multiple functional groups. This review summarizes current knowledge on the structures of dendrimer-based nanocarriers for natural compounds, with a particular focus on applications in alkaloids and polyphenols. Additionally, it highlights the challenges and perspectives for future development in clinical therapy.

Mono- and Bimetallic Aluminum Complexes Supported by Thioether-Amide Ligands: Synthesis, Characterization, and Application in the Ring Opening Polymerization of l-Lactide

Mono- and bimetallic aluminum complexes bearing bidentate NS or tetradentate NSSN ligands have been synthesized via reaction of AlMe3 with the corresponding proligand and spectroscopically characterized. In these complexes the aluminum centers are surrounded by anionic nitrogen and neutral sulfur atoms that, together with the carbon atoms of the alkyl groups, produce tetrahedral coordination geometries. In the bimetallic complexes the two metal centers are linked by a thioether-bridge of different lengths. The solid state structure of the complexes featuring the thioethyl or thiopropyl bridge were determined by X-ray diffraction studies. Both mono- and bimetallic aluminum complexes display fluxional behaviors in solution. After proper activation, all complexes were able to promote the ring opening polymerization of l-lactide in toluene solution. The polymerizations were well controlled as testified by the linear increase of the molecular weights with the conversions and the narrow polydispersity indexes. The highest activity was observed for the bimetallic complex bearing the NSSN ligand with the shortest bridge (ethyl bridge) with a turnover frequency of 11.6 molLA·molAl–1·h–1 (toluene, 80 °C). The activity decreased as the distance between the two metal centers increased. Moreover, the activity of the bimetallic complex with the ethyl bridge was higher than those of the monometallic ones. These findings suggest that a cooperative interaction between two aluminum centers is operative in the bimetallic complex with the shortest bridge.

Simulation and in vitro evaluations of microfluidically-fabricated clarithromycin-poly (ε-caprolactone) nanoparticles

Clarithromycin (CLR)-loaded poly (ε-caprolactone) (PCL) nanoparticles (NPs) were synthesized using microfluidics (MF) with square-shaped (MF1), and three-channel (MF2), geometries as well as conventional bulk mixing (BM). Based on Comsol simulation results of MF chips, the flow rate ratio, non-solvent phase flow rate, and polymer solution concentration were optimized 0.05, 50 mL h−1, and 0.2 (%w/v), respectively; thereby, representing MF1 geometry with highest homogenous mixing. Characterization studies indicated that MF1-based NPs possessed smaller average diameter (∼91 nm), narrower polydispersity index (∼0.13) and higher zeta potential (-44 mV) compared to those NPs synthesized by MF2 and BM methods. Moreover, MF1-aided synthesis of NPs exhibited the encapsulation efficiency of approximately 81% and loading capacity of around 13%. Investigating CLR release behavior at different pHs also demonstrated that the MF1-based NPs experienced the most controlled release, followed the Fickian diffusion mechanism. The controlled release of MF1-based NPs was confirmed by evaluating their inhibitory effect against specific cytokines on BEAS-2B as bronchitis cell line via a series of in vitro experiments including real time-polymerase chain reaction and flow cytometry. Eventually, the antibacterial properties of the samples were studied on two prevalent bacterial strains and the obtained observations revealed that MF1-based NPs encompassed the best performance in controlled release of CLR with respect to the other samples.

Polyether-Thiourea-Siloxane Copolymer Based on H-Bonding Interaction for Marine Antifouling.

By introducing thiourea and ether groups into MQ silicone resin polymer via free radical polymerization, a polyether-thiourea-siloxane (PTS) copolymer was synthesized. The characterization of the synthesized copolymer indicated the occurrence of H-bonding interactions and a narrow molecular weight polydispersity index. Antifouling coatings were produced by incorporating the synthesized copolymer and phenylmethylsilicone oil (PSO). The addition of a minute amount of copolymer enhanced the hydrophobicity of the coating by increasing its surface roughness. However, excessive addition of copolymer resulted in a significant deterioration of the coating surface smoothness. The copolymer improved the mechanical properties of the coating, but excessive addition decreased the crosslinking density and weakened the mechanical performance. With increasing copolymer addition, the leaching of PSO was significantly improved due to the change in the storage form of PSO in the coating caused by the copolymer. Based on the H-bonding interaction of the copolymer, the adhesion strength between the coating and the substrate was significantly improved. However, excessive addition of copolymer did not infinitely enhance the adhesion strength. The antifouling performance demonstrated that an appropriate amount of copolymer could obtain adequate PSO leaching efficiency, thereby effectively enhancing the antifouling performance of the coating. In this study, the prepared coating P12 (12 g of PTS in 100 g of PDMS) showed the most effective antifouling performance.

Abstract 835: Translational nanotechnology-based cancer vaccine to re-educate host immune response against metastatic cancers

Abstract Sixty percent of melanoma patients present brain metastases, having low response rates to current systemic therapies, which do not prolong survival. New therapeutic options to address this clinical need are urgent. Here, we report the development of a polymeric nanoparticle as a cancer nanovaccine capable of selectively co-targeting toll-like receptor function and PD-L1 expression to improve antigen presentation and subsequent effector immune cell function within brain microenvironment. Mannose-poly(lactic-co-glycolic acid)/poly(lactic acid) (man-PLGA/PLA) nanoparticles (NP) were prepared by a modified double emulsion solvent evaporation method, to deliver combinations of melanoma neoantigens, toll-like receptor ligands and regulators of the PD-1/PD-L1 axis. NP physicochemical properties were fully characterized, including size, surface charge and morphology. The amount of melanoma neoantigens and immune regulators entrapped within NP was determined by HPLC. Immature dendritic cells (DC) were used to evaluate the impact of NP on cell viability, and to assess NP uptake kinetics by flow cytometry. NP ability to target and trigger the activation of DC and T cells, was assessed in the lymph nodes and spleen of immunized mice. The NP anti-tumor immune-mediated effect was evaluated in vivo in two primary melanoma-bearing immunocompetent mouse models (B16F10 and B16MO5), and in a melanoma brain metastasis (MBM) mouse model (B16F10), which also included the immune profiling within tumor site by flow cytometry, before and after treatment.NP presented an average diameter of 180 nm, narrow polydispersity index, surface charge close to neutrality, spherical morphology, and high loadings of the neoantigens and immunoregulators. NP did not affect DC viability and were extensively internalized by immature DC. NP were preferentially taken-up in vivo by DC, increasing the expression of activation/maturation markers at DC surface, such as CD80 and CD86. NP elicited antigen-specific T-cell responses, by the significant increase in the expression of TNF-alpha and IFN-gamma (TH1-guided response). In vivo combination of NP with anti-PD-L1 induced a potent immune-mediated anti-tumor response in both primary and preclinical models of MBM, overcoming tumor development with an increased overall survival. This combination re-shaped immune and stroma cell populations in primary tumor and MBM microenvironment, which presented a marked infiltration of cytotoxic T cells that correlated with a decreased expression of PD-1 and PD-L1 within the TME. The synergy between our nanovaccine and anti-PD-L1 provide essential insights to devise alternative combinations regiments to improve the efficacy of immune checkpoint inhibitors in metastatic melanoma, thus opening new line for this unmet medical need. Citation Format: Barbara Carreira, Rita A. Acúrcio, Sabina Pozzi, Ron Kleiner, Liane I. Moura, Ana I. Matos, Daniela vaskovich, Carina Peres, Adelaide Fernandes, Sara Xapelli, Ronit Satchi-Fainaro, Helena F. Florindo. Translational nanotechnology-based cancer vaccine to re-educate host immune response against metastatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 835.

Organonitriles as complexing agents for the double metal cyanide-catalyzed synthesis of polyether, polyester, and polycarbonate polyols

A series of double metal cyanide (DMC) catalysts prepared using nitrile compounds as complexing agents (CAs) was employed for the synthesis of polyether, polyester, and polycarbonate polyols. The DMC catalysts bearing nitrile CAs exhibited remarkably higher activities toward the ring-opening polymerization (ROP) of propylene oxide (PO) and ε-caprolactone (CL), as well as toward the copolymerization of PO with CO2, than conventional DMC catalysts prepared using tert-butyl alcohol as a CA. Accordingly, DMC catalysts bearing 2-methylbutyronitrile or isobutyronitrile showed the highest activities for the ROP of PO (TOF=533 min−1) and CL (TOF=83 h−1), respectively, whereas the DMC using acetonitrile CA exhibited the highest efficiency for the copolymerization of PO and CO2 (TOF=475 h−1). The resultant polypropylene oxide polyols were characterized by a narrow polydispersity index (1.1 −1.2) and a low unsaturation level (0.004−0.014). In addition, the DMC catalyst bearing isobutyronitrile afforded α,ω-hydroxyl-terminated polycaprolactones with controlled molecular weights (1000−9800 g mol−1) and a narrow polydispersity index of 1.1−1.5. Polycarbonate polyols with relatively high yields (56–67 %) and carbonate contents (30–38 %) were also obtained.

Impact of Operating Parameters on the Production of Nanoemulsions Using a High-Pressure Homogenizer with Flow Pattern and Back Pressure Control

The main objective of this study was to establish the relative importance of the main operating parameters impacting the formation of food-grade oil-in-water nanoemulsions by high-pressure homogenization. The goal of this unit operation was to create uniform and stable emulsified products with small mean particle diameters and narrow polydispersity indices. In this study, we examined the performance of a new commercial high-pressure valve homogenizer, which has several features that provide good control over the particle size distribution of nanoemulsions, including variable homogenization pressures (up to 45,000 psi), nozzle dimensions (0.13/0.22 mm), flow patterns (parallel/reverse), and back pressures. The impact of homogenization pressure, number of passes, flow pattern, nozzle dimensions, back pressure, oil concentration, emulsifier concentration, and emulsifier type on the particle size distribution of corn oil-in-water emulsions was systematically examined. The droplet size decreased with increasing homogenization pressure, number of passes, back pressure, and emulsifier-to-oil ratio. Moreover, it was slightly smaller when a reverse rather than parallel flow profile was used. The emulsifying performance of plant, animal, and synthetic emulsifiers was compared because there is increasing interest in replacing animal and synthetic emulsifiers with plant-based ones in the food industry. Under fixed homogenization conditions, the mean particle diameter decreased in the following order: gum arabic (0.66 µm) &gt; soy protein (0.18 µm) &gt; whey protein (0.14 µm) ≈ Tween 20 (0.14 µm). The information reported in this study is useful for the optimization of the production of food-grade nanoemulsions using high-pressure homogenization.

Preparation of Polystyrene/Polyacrylamide Core-Shell Microspheres via Microfluidizer-Assistant Emulsification Template Methods for Oil Recovery Enhancement

Polyacrylamide and its derivatives are commonly used functional polymers to enhance oil recovery in a water-flooding oilfield. By using its hydrophilic amide group to swell and gel in stratum water, it can plug the fractures and pore throats of underground. In order to improve the strength of polyacrylamide material, the polystyrene/polyacrylamide (PS/PAM) core-shell microspheres were successfully prepared by the microfluidizer-assistant emulsification template method. The influences of different preparation conditions, such as the different types and concentrations of surfactants, organic phase and oil/water ratios, on the morphology, diameter, and distribution of corresponding PS core have been systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and laser light scattering analysis (LLS). Moreover, by the integration of porous meshes onto both inlet and outlet of the interaction chamber, the resultant polymer microspheres could be tuned larger due to the dual homogenization. Our procedure can provide a simple and general method to modulate the diameter of the polymer microspheres in the range of 30 nm to 3 μm with a narrow polydispersity index (PDI) of <0.2. The PS/PAM core-shell microspheres exhibited good water plugging performance.

Biosynthesis of pectic oligosaccharide-based amphiphiles as novel stabilizers of nanoemulsions by coupling enzymatic depolymerization with alkyl/alkenyl succinylation

Pectic oligosaccharides (POS) are gaining increasing recognition as a novel kind of prebiotics. Here, a new multipurpose amphiphilic POS was synthesized by coupling pectinase-mediated depolymerization of citrus pectin with lipase-catalyzed alkyl succinylation. Structural characterization by thin-layer chromatography, size exclusion chromatography, mass spectrometry, Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance, and transmission electron microscopy showed that POS obtained by enzymatic hydrolysis consisted mainly of octamers and hexamers and was subsequently hydrophobically functionalized by reaction with alkylsuccinic anhydrides of various alkyl chain lengths to develop amphiphilic properties. Emulsions stabilized by pectin and alkylsuccinylated POS were assessed by analysis of droplet size distribution, zeta potential, and confocal fluorescence microscopy. The results showed that POS-derived amphiphiles POS-SA12 and POS-SA22 (alkyl C12 and C22) formed stable nanoemulsions with mean particle size of <200 nm and a narrow polydispersity index of <0.20, compared to pectin-based microemulsions (>1100 nm in size and >0.8 polydispersity index). Differences were largely ascribed to the well-balanced hydrophobicity of the introduced alkyl group and the hydrophilicity of the carboxyl groups in the molecular structure of POS-SA12. Our study introduces a green synthetic approach for the production of a novel POS-derived amphiphile with prebiotic and emulsifying properties showing excellent performance in stabilizing oil/water emulsions and other extensive applications.

Degradation of Alkaline Lignin in the Lactic Acid-Choline Chloride System under Mild Conditions

Lignin is a natural polymer, second only to cellulose in natural reserves. Degradation is one of the ways to achieve the high-value transformation of lignin. Deep eutectic solvent (DES) thermal degradation of lignin can be used as an excellent green degradation method. This paper introduces the degradation mechanism and effect of the lactic acid-choline chloride DES system in dissolving and degrading alkaline lignin, and the final solvent recovery. It can also be found from the scanning electron microscope (SEM) images that the surface of the degraded solid product is transformed from smooth to disordered. Fourier transform infrared (FTIR) spectroscopy and 1 H-NMR spectroscopy were used to characterize the changes in lignin functional groups during DES treatment. The results showed that the content of phenolic hydroxyl groups increased after degradation, indicating that the β-O-4 ether bond was broken. The molecular weight of the degraded lignin was observed by gel permeation chromatography (GPC), and the lignin residue with low molecular weight and narrow polydispersity index was obtained. The lowest average molecular weight (Mw) reached 2512 g/mol. The ratio of oxygen to carbon atoms in lignin increased substantially during degradation as measured by X-ray photoelectron spectroscopy (XPS), probably because DES treatment was accompanied by many oxidation reactions, which led to significant structural changes in lignin and a large number of ether bond breakage reactions during the reaction. The main final degradation products are aromatic monomers, vanillin, butyrovanillone, etc.

A simple but novel glycymicelle ophthalmic solution based on two approved drugs empagliflozin and glycyrrhizin: in vitro/in vivo experimental evaluation for the treatment of corneal alkali burns.

A simple but novel ophthalmic solution based on two approved drugs was developed to reposition existing drugs to treat new diseases. This nanoformulation was developed using the phytochemical drug glycyrrhizin as an amphiphilic nanocarrier to micellarly solubilize empagliflozin (EMP), an oral drug that is widely used to control high blood glucose but has poor water solubility. This novel nanoformulation, which we designated the EMP@glycymicelle ophthalmic solution, was obtained using a simple preparation process. The resulting solution was a clear solution with an EMP encapsulation efficiency of 97.91 ± 0.50%, a small glycymicelle size of 6.659 ± 0.196 nm, and a narrow polydispersity index of 0.226 ± 0.059. The optimized formulation demonstrated that EMP was soluble in water up to 18 mg ml-1 because of its encapsulation within glycymicelles. The EMP@glycymicelle ophthalmic solution exhibited excellent characteristics, including good storage stability, fast in vitro release profiles, improved in vitro antioxidant activity, and no ocular irritation. Ocular permeation evaluation showed that the EMP@glycymicelle ophthalmic solution had strong ocular permeation of EMP, and it reached the posterior segment of mouse eyes after ocular topical administration. The treatment efficacy evaluation showed that the EMP@glycymicelle ophthalmic solution had a significant effect against corneal alkali burns in mice, prompting corneal wound healing, recovering corneal sensitivity, reducing corneal haze, and relieving corneal NV invasion. The mechanism of inhibiting HMGB1 signaling was involved in this strong treatment effect. These results indicated that the EMP@glycymicelle ophthalmic solution provided a new concept of drug repurposing and a promising ocular system for the nano-delivery of EMP with significantly improved in vivo profiles.

Emulgel-loaded mannosylated thiolated chitosan-coated silver nanoparticles for the treatment of cutaneous leishmaniasis

Topical treatment of cutaneous leishmaniasis holds great promise for decreasing drug associated side effects and improving efficacy. This study was aimed to develop mannosylated thiolated chitosan-coated silver nanoparticles (MTCAg) loaded emulgel for the treatment of cutaneous leishmaniasis. MTC-Ag were synthesized via a chemical reduction method and were loaded into the emulgel. The nanoparticles had a zeta potential of +19.8 mV, an average particle size of 115 nm and a narrow polydispersity index of 0.26. In-vitro release profiles showed controlled release of silver ions from both the MTC-Ag and the emulgel-loaded MTC-Ag nanoparticles after 24 h. An ex-vivo retention study indicated 5 times higher retention of silver by the emulgel-loaded MTC-Ag than by the MTC-Ag nanoparticles. The in-vitro anti-leishmanial assay revealed that MTC-Ag had an excellent inhibitory effect on intracellular amastigotes, leading to ~90 % inhibition at the highest concentration tested. A 4-fold reduction in the IC50 value was found for MTC-Ag compared to blank Ag nanoparticles. Cytotoxicity assay showed 83 % viability of macrophages for MTC-Ag and 30 % for Ag nanoparticles at a concentration of 80 μg/mL, demonstrating the improved biocompatibility of the polymeric nanoparticles. Drug release and retention studies corroborate the great potential of MTC-Ag-loaded emulgel for the treatment of cutaneous leishmaniasis.

Piper aduncum Essential Oil Rich in Dillapiole: Development of Hydrogel-Thickened Nanoemulsion and Nanostructured Lipid Carrier Intended for Skin Delivery.

The essential oil extracted from the leaves of Piper aduncum, an aromatic plant from the Amazon region, is rich in dillapiole and presents anti-inflammatory activity. In this study, nanoemulsions (NE) and nanostructured lipid carriers (NLC), which are biocompatible nanostructured systems of a lipid nature, were prepared by high-pressure homogenization for the yet unexplored skin delivery of dillapiole. The addition of hydroxyethylcellulose produced hydrogel-thickened NE or NLC in view to improving the viscosity and skin adherence of the nanoformulations. Formulations were characterized with respect to dillapiole content, droplet size, polydispersity index, zeta potential, morphology, rheological behavior, bioadhesion, skin permeation profile, and in vitro irritancy (HET-CAM). The formulations developed presented spherical, homogeneous nanometric particle size (around 130 nm), narrow polydispersity index (&lt;0.3), and negative zeta potential (around -40 mV). Dillapiole content was slightly lower in NLC compared to NE since the production process involves heating. The hydrogels containing nanocarriers showed pseudoplastic behavior with bioadhesive characteristics. The developed formulations exhibited a controlled release profile, dillapiole delivery up to the dermis, the layer of interest for anti-inflammatory potential, and low irritant potential in the chorioallantoic membrane (HET-CAM). Both hydrogels-thickened NE and NLC seemed to be promising formulations for skin delivery of Piper aduncum essential oil.

Easy access to ultra-high molecular weight polylactones using a bismuth catalyst

A facile method for the preparation of ultra-high molecular weight of polylactides and poly(ε-caprolactone) with relatively narrow polydispersity index using BiPh2Br catalyst is presented. Ultra-high molecular weight PLLA (Mw = 1.75 × 106 g/mol, Đ = 2.0, yield = 84 %) and PDLA (Mw = 1.58 × 106 g/mol, Đ = 2.0, yield = 84 %) having unprecedented molecular weights were synthesized by ring-opening polymerization (ROP) of the L- and D- lactides without any monomer purification and any co-initiators. Ultra-high molecular weight PCL having an unprecedented molar mass of 1.58 × 106 g/mol has also been achieved by ROP of ε-caprolactone without any monomer purification and co-initiators. Effects of initiator concentration, catalyst concentration, polymerization temperature and time on the molecular weight of poly-L-lactide are also investigated. The catalyst activation reaction mechanism in the absence of a co-initiator has been further studied by MALDI-TOF-MS, low and high-temperature 1H NMR and Fourier-Transform Ion-Cyclotron-Resonance Mass Spectrometry, elucidating the activation mechanism of the BiPh2Br catalyst precursor by the water from the monomer and revealing the formation of two active species: BiPh2OR and BiPh(OR)Br. DFT calculations reveal a high energy demand (25 kcal/mol) for the chain transfer to water compared with the ROP of the complex used, supporting the evidence for the synthesis of UHMW polymers. The resulting polymers have been characterized by DSC, GPC and MALDI-TOF-MS; MALDI-TOF-MS proves the presence of linear as well as macrocyclic structures for the molecular weight range detected.