Colloidal Formulations Research Articles

Advancements in Cancer Therapeutics: Current Paradigms in Applying Biodegradable Polymer Nanoparticles for Enhanced Management

Abstract: The development of novel colloidal formulations that can regulate the pharmacological and biological properties of medications has been made possible by the developments of nanotechnology. Biodegradable nanoparticles were exploited as drug delivery methods because of their high bioavailability, improved encapsulation, controlled release, and less toxic characteristics. Over the past few decades, a variety of synthetic polymers have been investigated for application in nanomedicine, particularly in drug delivery systems. Drug delivery polymers need to be environmentally friendly, biodegradable, and biocompatible. As they have the ability to provide targeted delivery to a specified site, polymeric nanoparticles have the potential to increase the effectiveness of cancer therapies significantly. It is possible to modify the physical and chemical characteristics of polymers to provide delivery across the many biological barriers needed to reach different cell subsets. The use of biodegradable polymers as nanocarriers is particularly appealing since these materials can be developed to show triggered functionality at certain locations or activated by an external source in addition to degrading under physiological circumstances. Biodegradable polymers can be developed as easy drug-delivery systems that specifically target the tumour microenvironment. This is because these nanomedicines can directly target cancer cells, as well as blood vessels that supply the nutrition and oxygen required for tumour growth and immune cells that support anti-cancer immunotherapy. With the advancements in nanotechnology-based drug delivery systems for pharmaceutical applications, it is exciting to examine and highlight the significance of polymeric nanocarrier systems for drug delivery in chemotherapy.

Silversol® (a Colloidal Nanosilver Formulation) Inhibits Growth of Antibiotic-Resistant Staphylococcus aureus by Disrupting Its Physiology in Multiple Ways.

Antibiotic-resistant strains of Staphylococcus aureus are being viewed as a serious threat by various public health agencies. Identifying novel targets in this important pathogen is crucial to the development of new effective antibacterial formulations. We investigated the antibacterial effect of a colloidal nanosilver formulation, Silversol®, against an antibiotic-resistant strain of S. aureus using appropriate in vitro assays. Moreover, we deciphered the molecular mechanisms underlying this formulation's anti-S. aureus activity using whole transcriptome analysis. Lower concentrations of the test formulation exerted a bacteriostatic effect against this pathogen, and higher concentrations exerted a bactericidal effect. Silversol® at sub-lethal concentration was found to disturb multiple physiological traits of S. aureus such as growth, antibiotic susceptibility, membrane permeability, efflux, protein synthesis and export, biofilm and exopolysaccharide production, etc. Transcriptome data revealed that the genes coding for transcriptional regulators, efflux machinery, transferases, β-lactam resistance, oxidoreductases, metal homeostasis, virulence factors, and arginine biosynthesis are expressed differently under the influence of the test formulation. Genes (argG and argH) involved in arginine biosynthesis emerged among the major targets of Silversol®'s antibacterial activity against S. aureus.

Effects of Anionic Liposome Delivery of All-Trans-Retinoic Acid on Neuroblastoma Cell Differentiation.

All-trans-retinoic acid (ATRA) has long been known to affect cell growth and differentiation. To improve ATRA's therapeutic efficacy and pharmacodynamics, several delivery systems have been used. In this study, free ATRA and anionic-liposome-encapsulated ATRA were compared for their effects on SK-N-SH human neuroblastoma cell growth and differentiation. Anionic liposomes made of L-α-phosphatidylcholine (PC) and L-α-phosphatidic acid (PA), empty (PC-PA) and loaded with ATRA (PC-PA-ATRA), were characterized by dynamic light scattering (DLS) and electrophoretic mobility measurements, and drug entrapment efficiency (EE%) was measured to evaluate the applicability of the new colloidal formulation. The results of brightfield microscopy and cell growth curves indicated that ATRA, whether free or encapsulated, reduced growth and induced differentiation, resulting in SK-N-SH cells changing from epithelioid to neuronal-like morphologies, and producing a significant increase in neurite growth. To further characterize the neuro-differentiation of SK-N-SH cells, the expression of βIII-Tubulin and synaptophysin and mitochondria localization were analyzed via immunofluorescence. Increased expression of neuronal markers and a peculiar localization of mitochondria in the neuritic extensions were apparent both in ATRA- and PC-PA-ATRA-differentiated cells. As a whole, our results strongly indicate that ATRA treatment, by any means, can induce the differentiation of parent SK-N-SH, and they highlight that its encapsulation in anionic liposomes increases its differentiation ability in terms of the percentage of neurite-bearing cells. Interestingly, our data also suggest an unexpected differentiation capability of anionic liposomes per se. This work highlights the importance of developing and carefully testing novel delivery nanocarriers, which are a necessary first "step" in the development of new therapeutic settings.

Bioinspired zwitterionic triblock copolymers designed for colloidal drug delivery: 2 - Biological evaluation

In this work, poly(lactide) nanoparticles were equipped with a bioinspired coating layer based on poly[2-(methacryloyloxy)ethyl phosphorylcholine] and then evaluated when administered to the lungs and after intravenous injection. Compared to the plain counterparts, the chosen zwitterionic polymer shell prevented the coated colloidal formulation from aggregation and conditioned it for lower cytotoxicity, protein adsorption, complement activation and phagocytic cell uptake. Consequently, no interference with the biophysical function of the lung surfactant system could be detected accompanied by negligible protein and cell influx into the bronchoalveolar space after intratracheal administration. When injected into the central compartment, the coated formulation showed a prolonged circulation half-life and a delayed biodistribution to the liver. Taken together, colloidal drug delivery vehicles would clearly benefit from the investigated poly[2-(methacryloyloxy)ethyl phosphorylcholine]-based polymer coatings.

Formulation and In-vivo Characterization of 177Lu-tin-colloid as a Radiosynovectomy Agent.

Arthritis is an inflammatory disorder that affects one or more joints of the body for various reasons, including autoimmune disorders, trauma, or infection. In many cases, traditional long-term treatment with various drug combinations (NSAIDs, diseasemodifying antirheumatic drugs, systemic corticosteroids, etc.) can provide relief, but many joints require additional local treatment. Radiosynovectomy (RSV) is an alternative method to current treatment options. Both the global supply shortage of 90Y in recent years and the increasing use of 177Lu-labeled radiopharmaceuticals in the field of nuclear medicine have made it possible to develop 177Lu-labeled microparticles and test them in small groups as RSV agents. This study aimed to develop the 177Lu labeled tin colloid formulation and demonstrate its invivo characterization. Particle size, shape, and labelling efficiency of the four formulations developed were determined. The formula with the highest labelling efficiency was selected for further studies. The quality of the formulation was evaluated based on radionuclidic, radiochemical, and microbial purity. In-vitro stability was evaluated by determining the labelling efficiency. In-vitro stability was tested in PBS and synovial fluid. The biological characterization was assessed using SPECT/CT after injecting the formulation into the normal knee joints of the rabbits. Aggregated colloidal particles were spherical with a particle size of <5 μm. Labelling efficiency and radiochemical purity were >95 and 97.65% (Rf=0.2), respectively. The formulation was stable in vitro for up to 72 hours, both in PBS and synovial fluid. The formulation was homogeneously distributed in the joint at 0 and 1 hour after injection, and radioactivity- related involvement and inguinal lymph node involvement due to possible leakage were not detected in the late period. No pyrogenic/allergic side effects were observed during this period. 177Lu-tin-colloid was successfully prepared under optimized reaction conditions with high binding efficiency and radiochemical purity. The radiolabeled colloid was found to be stable in-vitro both in PBS and synovial fluid at room temperature. Serial PCET/CT images revealed that the activity was completely retained within the synovial cavity, with no activity leakage out of the joint until 48 hours after the injection. With the support of the results from further clinical studies, it may be possible for the formulation to enter clinical use.

Cutaneous Delivery and Biodistribution of Cannabidiol in Human Skin after Topical Application of Colloidal Formulations.

The objective of this study was to investigate the cutaneous delivery of cannabidiol (CBD) from aqueous formulations developed for the targeted local treatment of dermatological conditions. CBD was formulated using a proprietary colloidal drug delivery system (VESIsorb®) into an aqueous colloidal solution at 2% (ACS 2%) and two colloidal gels (CG 1% and CG 2%, which contained 1% and 2% CBD, respectively). Two basic formulations containing CBD (5% in propylene glycol (PG 5%) and a 6.6% oil solution (OS 6.6%)) and two marketed CBD products (RP1 and RP2, containing 1% CBD) were used as comparators. Cutaneous delivery and cutaneous biodistribution experiments were performed using human abdominal skin (500-700 µm) under infinite- and finite-dose conditions with 0.5% Tween 80 in the PBS receiver phase. The quantification of CBD in the skin samples was performed using a validated UHPLC-MS/MS method and an internal standard (CBD-d3). The cutaneous deposition of CBD under finite-dose conditions demonstrated the superiority of CG 1%, CG 2%, and ACS 2% over the marketed products; CG 1% had the highest delivery efficiency (5.25%). Cutaneous biodistribution studies showed the superiority of the colloidal systems in delivering CBD to the viable epidermis, and the upper and lower papillary dermis, which are the target sites for the treatment of several dermatological conditions.

(Invited) In Situ Characterization during Electrode Processing: The Role of Hidden Parameters

Micron and nano-sized functional materials play a key role for future technologies that are currently developed in the field of energy conversion (electrolysers, fuel cells) and electrocatalysis (N2 fixation, CO2 reduction reaction). While new materials with outstanding properties are continuously developed, they rarely find their way into – urgently needed – large scale production and industrial applications.1 One reason for this are hidden parameters that occur during ink formulation, coating (and decal transfer), cell assembly, and operation. We propose the development of coherent workflows that help us to identify reliable correlations. These should be developed for each electrocatalyst, bridging synthesis, electrode and gas diffusion electrode (GDE) / membrane electrode assembly (MEA) fabrication, and testing. All information, including “negative” results like crack formation, delamination, structural ageing and dissolution, must be reported until the relevant hidden parameters are deciphered, and the design chain is understood. Then, materials and electrodes derived from complementary processes and exhibiting subtle variations in composition and structure, can be evaluated against each other.However, this implies to fill the “blackbox” between technical catalysts and electrochemical testing in flow cells, GDEs or MEAs, with quantitative data on powders, ink formulations and coating properties. In the past years, we developed a toolbox of methods that starts from key control characteristics for technical catalysts, i.e., Pt/C for polymer electrolyte membrane fuel cells, that thereon enable the in situ analysis of ink formulations and pastes during the dispersion process and at application concentration.2,3 This is followed by the assessment of the resulting coatings from large-area crack analysis down to the level of surface roughness and pore size characteristics.4 Finally, this input is connected with performance and stability testing results to enable the comparison of different materials, the assessment of structure property relations, and ultimately to establish inline process control during electrode manufacturing. In this contribution, the developed methods will be summarized and related to their current limitations and prospects, in particular for unraveling hidden parameters during electrode fabrication and MEA assembly as well as in line process control. Literature [1] Siegmund, Daniel; Metz, Sebastian; Peinecke, Volker; Warner, Terence E.; Cremers, Carsten; Grevé, Anna; Smolinka, Tom; Segets, Doris; Apfel, Ulf-Peter; Crossing the Valley of Death : From Fundamental to Applied Research in Electrolysis, JACS Au 1 (2021), 527 – 535.[2] Bapat, Shalmali; Segets, Doris; Sedimentation Dynamics of Colloidal Formulations through Direct Visualization : Implications for Fuel Cell Catalyst Inks, ACS Applied Nano Materials 3 (2020), 7384 – 739.[3] Bapat, Shalmali; Giehl, Christopher; Kohsakowski, Sebastian; Peinecke, Volker; Schäffler, Michael; Segets, Doris; On the state and stability of fuel cell catalyst inks, Advanced Powder Technology 32 (2021), 3845 – 3859.[4] Jaster, Theresa; Albers, Simon; Leonhard, Armin; Kräenbring, Mena-Alexander; Lohmann, Heiko; Zeidler-Fandrich, Barbara; Özcan, Fatih; Segets, Doris; Apfel, Ulf-Peter; Enhancement of CO₂RR product formation on Cu-ZnO-based electrodes by varying ink formulation and post-treatment methods, JPhys Energy 5 (2023), 024001.

Sub-lethal concentration of a colloidal nanosilver formulation (Silversol®) triggers dysregulation of iron homeostasis and nitrogen metabolism in multidrug resistant Pseudomonas aeruginosa

BackgroundPseudomonas aeruginosa is a notorious pathogen. Its multidrug resistant strains are listed among priority pathogens against whom discovery of novel antibacterial agents and, elucidation of new anti-pathogenicity mechanisms are urgently warranted. This study describes multiple antibacterial effects of a colloidal nano-silver formulation- Silversol® against a multi-drug resistant strain of P. aeruginosa.ResultsMinimum inhibitory concentration (MIC) of Silversol® against P. aeruginosa was found to be 1.5 ppm; and at sub-MIC of 1 ppm, it was able to alter quorum-sensing regulated pigmentation (pyocanin 82%↓; pyoverdine 48%↑), exopolysaccharide synthesis (76%↑) and biofilm formation, susceptibility to antibiotics (streptomycin and augmentin), protein synthesis and export (65%↑), nitrogen metabolism (37%↑ nitrite accumulation), and siderophore production in this pathogen. Network analysis of the differentially expressed genes in the transcriptome of the silversol-treated bacterium identified ten genes as the potential molecular targets: norB, norD, nirS, nirF, nirM, nirQ, nosZ, nosY, narK1, and norE (all associated with nitrogen metabolism or denitrification). Three of them (norB, narK1, and norE) were also validated through RT-PCR.ConclusionsGeneration of nitrosative stress and disturbance of iron homeostasis were found to be the major mechanisms associated with anti-Pseudomonas activity of Silversol®.

An Analytical Method for Determination of Total Iron in Pharmaceuticalgrade Intravenous Iron Colloidal Complexes by Redox-Potentiometry.

Iron carbohydrate complexes are colloidal dispersions made up of polynuclear Fe(III)-oxyhydroxide cores surrounded by a carbohydrate shell that stabilizes the complex in iron colloidal formulations. The current study provides an improved method that is precise, accurate, and linear for quantifying total iron in most Iron Carbohydrate Colloid Drug Products. Redox iodometry with a potentiometric determination is used to evaluate total iron in intravenous formulations. The visual indicator approach is more prone to fluctuations at endpoint calculations. Hence, the voltage potential approach is widely accepted as it is more accurate and sensitive. It tracks the actual change in activity that coincides with the equivalence point that is finally considered an endpoint. The principle is based on the idea that ferric iron in formulation reduces to ferrous iron in the presence of the iodide, which oxidizes to iodine. The released iodine is titrated using sodium thiosulfate. The proposed method was precise, with %RSD (relative standard deviation) not more than 1. The method was linear between 80% and 120%, with a linear regression of 0.999. The percent recovery ranged from 98.20 to 99.98 for the concentration ranges of 80-120. The method's robustness was checked by various analysts using different reagent grades. The proposed potentiometric determination method was precise, accurate, linear, and sensitive. The method was successfully validated, and the total iron content determined for commercial batches agrees with the iron claim on the label. Therefore, this method can be adapted widely for total iron content determination in any Intravenous formulation currently available on the market. The proposed method is more accessible at the Quality Control facilities on an industrial scale.

Phase diagrams and property of colloidal systems prepared with an alkyl polyglucoside surfactant and the essential oil of Melaleuca alternifolia (tea tree)

BackgroundThe purpose of this study was to develop the colloidal formulation, based on microemulsions and hydrogels, of Melaleuca alternifolia oil (aka tea tree oil, TTO) using a sustainable and biocompatible alkyl polyglucoside (APG) surfactant, Glucopon 600 CSUP (G600), commonly formulated for personal-care and home-care products. MethodsThe pseudo-ternary phase diagram of TTO-mixed surfactant-water was established with the water titration method at 25 °C. The mixed surfactants were composed of G600 and propylene glycol (PPG) as a co-surfactant at G600/PPG = 1/1, 2/1 and 3/1 (m/m). Colloid samples of one phase were further characterized with rheological measurements and dynamic light scattering (DLS) at 25 °C. Significant findingsThe samples containing TTO/mixed surfactant = 1/9 (m/m) and water show single phase only. With increasing water contents, the aforesaid system changed from Newtonian to pseudo-plastic, reflecting the transition from micellar solution / microemulsion to hydrogel. Especially, the gel-like behavior was confirmed with the dynamic oscillatory measurements, in which storage moduli were always larger than loss moduli at any time and any frequency under a constant strain of 0.5 %. Microemulsions made of 1 wt% tea tree oil and 9 wt% mixed surfactants were stable for > 1 month as monitored by aggregate size by DLS.

Potent anthelmintic activity of a colloidal nano-silver formulation (Silversol®) against the model worm Caenorhabditis elegans

ObjectiveIn the background of a very small number of effective anthelmintics available today with a narrow activity spectrum, and a rise in resistance against them among parasitic helminths, there is an urgent need for discovery of novel broad-spectrum anthelmintics displaying no or minimal toxicity towards the host. Silver being used since centuries for therapeutic purposes and considered safe for human consumption, we investigated anthelmintic activity of a colloidal nanosilver formulation Silversol®. Anthelmintic efficacy of the test formulation was assayed employing the nematode Caenorhabditis elegans as a model worm through a live-dead count.ResultsSilversol® exerted anthelmintic action superior to one of the positive controls (Benzimidazole), and almost at par to another positive control (Ivermectin). At concentrations ≥ 2 ppm, it could kill all the worms present in the experimental well. Lower concentrations of silver were found to have a cuticle-damaging action on worms. Further investigation is warranted to assess whether Silversol® can exert similar potent activity against different species of parasitic helminths, and elucidate the underlying molecular mechanisms of action.

RGD-decorated PLGA nanoparticles improved effectiveness and safety of cisplatin for lung cancer therapy

Upon extensive pharmaceutical and biomedical research to treat lung cancer indicates that lung cancer remains one of the deadliest diseases and the leading cause of death in men and women worldwide. Lung cancer remains untreated and has a high mortality rate due to the limited potential for effective treatment with existing therapies. This highlights the urgent need to develop an effective, precise and sustainable solutions to treat lung cancer. In this study, we developed RGD receptor-targeted PLGA nanoparticles for the controlled and targeted co-delivery of cisplatin (CDDP) and upconversion nanoparticles (UCNP) in lung cancer therapy. Pluronic F127-RGD conjugate was synthesized by carbodiimide chemistry method and the conjugation was confirmed by FTIR and 1HNMR spectroscopy techniques. PLGA nanoparticles were developed by the double emulsification method, then the surface of the prepared nanoparticles was decorated with Pluronic F127-RGD conjugate. The prepared formulations were characterized for their particle size, polydispersity index, zeta potential, surface morphology, drug encapsulation efficiency, and in vitro drug release and haemolysis studies. Pharmacokinetic studies and safety parameters in BAL fluid were assessed in rats. Histopathology of rat lung tissue was performed. The obtained results of particle sizes of the nanoparticle formulations were found 100–200 nm, indicating the homogeneity of dispersed colloidal nanoparticles formulations. Transmission Electron Microscopy (TEM) revealed the spherical shape of the prepared nanoparticles. The drug encapsulation efficiency of PLGA nanoparticles was found to range from 60% to 80% with different nanoparticles counterparts. RGD receptor-targeted PLGA nanoparticles showed controlled drug release for up to 72 h. Further, RGD receptor-targeted PLGA nanoparticles achieved higher cytotoxicity in compared to CFT, CFT, and Ciszest-50 (marketed CDDP injection). The pharmacokinetic study revealed that RGD receptor-targeted PLGA nanoparticles were 4.6-fold more effective than Ciszest-50. Furthermore, RGD receptor-targeted PLGA nanoparticles exhibited negligible damage to lung tissue, low systemic toxicity, and high biocompatible and safety in lung tissue. The results of RGD receptor-targeted PLGA nanoparticles indicated that it is a promising anticancer system that could further exploited as a potent therapeutic approach for lung cancer.

In Situ Self-Assembly of Nanoscale Particles into Macroscale Ordered Monolayers with Enhanced Memory Performance.

In situ fabrication of macroscale ordered monolayers of nanoparticles (NPs) on targeted substrates is highly desirable for precision electronic and optical devices, while it remains a great challenge. In this study, a solution is provided to address this challenge by developing a colloidal ink formulation and employing the direct-ink-writing (DIW) technique, where on-demand delivery of ink at a targeted location and directional evaporation with controllable rate are leveraged to precisely guide the deposition of polystyrene-grafted gold NPs (Au@PS NPs) into a macroscale monolayer with an ordered Au NP array embedded in a PS thin film. A 2D steady-state diffusion-controlled evaporation model, which explains the parameter dependence of the experimental results and gives semiquantitative agreement with the experimental evaporation kinetics is proposed. The ordered monolayer is used as both nanocrystal floating gates and the tunneling layer for nonvolatile memory devices. It shows significantly enhanced performance compared with a disordered NP film prepared by spin coating. This approach allows for fine control of NP self-assembly to print macroscaleordered monolayers directly onto substrates, which has great promise for application in broad fields, including microelectronic and photoelectronic devices, sensors, and functional coatings.

Organic green route synthesis of multifunctional colloidal sulfur formulation for pesticidal application

Crop protection through multifunctional low dimensional sulfur particles has numerous benefits over conventional chemical pesticides and formulations based on colloidal sulfur are emerging recently. A simple wet chemical route with acetic acid-thiosulphate-SDS system was reported to produce an aqueous colloidal sulfur formulation (CSF) of size ∼190 ​nm. This formulation was also stabilized with plant protective additives (neem oil, chitosan, tannic acid) and Taguchi methodology was applied to optimize the process and improve the stability of the formulation. Microscopic studies revealed that sulfur particles in the formulation are free from agglomerates and the developed formulation was investigated for antimicrobial and insecticidal activities. CSF was found to be effective on the tested phytopathogens (Aspergillus terreus, Fusarium solani and Venturia inequalis) with the supportive zone of inhibition and radial growth assays. Furthermore, CSF spraying onto the Pseudococcus mealybugs resulted in >80% mortality in 24 ​h and electron microscopy analysis displayed ultrastructural variations in the bodies of the insects with distorted morphology. CSF (with 18 ​mM sulfur) being non-toxic to earthworms and with its multifunctional properties could protect a wide range of crops. Its application as a foliar spray has the potential to replace commercial toxic pesticides.

Dietary-Polysaccharide-Modified Fish-Oil-Based Double Emulsion as a Functional Colloidal Formulation for Oral Drug Delivery.

Oral delivery is the most convenient drug administration route. However, oral delivery of peptides is extremely challenging due to the physical and chemical barriers within the gastrointestinal tract. Polysaccharides are often utilized as polymeric biomaterials in drug delivery. Among these, dietary polysaccharides extracted from okra, yam, and spirulina have been reported to stimulate innate immunity with well-known nutritional benefits. In this study, we developed a dietary-polysaccharide-modified fish-oil-based emulsion for oral co-delivery of a hydrophilic PD-L1 blocking peptide and the hydrophobic small molecule simvastatin. The optimal emulsion was nano-sized and exhibited a negative surface charge, high drug encapsulation efficiency of over 97%, low viscosity, and sustained drug release manner. The formulation could significantly increase the uptake of peptides by intestinal Caco-2 cells, which demonstrated the great potential of the formulation for promoting the oral absorption of peptides. Additionally, these dietary polysaccharides could promote dendritic cell maturation and cytokine expression in macrophages, demonstrating that these nutraceutical polysaccharides had dual roles of functioning as promising colloidal delivery systems and as potential immune modulators or adjuvants. Thus, this food-based colloidal delivery system shows promise for the oral delivery of peptide drugs and lays a great platform for future applications in immunotherapy.

Biomass-Derived Plant Extracts in Macromolecular Chitosan Matrices as a Green Coating for PLA Films.

Due to the growing problem of food and packaging waste, environmental awareness, and customer requirements for food safety, there is a great need for the development of innovative and functional packaging. Among these developments, the concept of active packaging is at the forefront. The shortcoming in this area is that there is still a lack of multifunctional concepts, as well as green approaches. Therefore, this work focuses on the development of active chemical substances of natural origin applied as a coating on polylactic acid (PLA) films. Biopolymer chitosan and plant extracts rich in phenolic compounds (blackberry leaves-Rubus fruticosus, needles of prickly juniper-Juniperus oxycedrus) obtained from plant biomass from Southeastern Europe were selected in this work. In order to increase the effectiveness of individual substances and to introduce multifunctionality, they were combined in the form of different colloidal structural formulations. The plant extracts were embedded in chitosan biopolymer particles and dispersed in a macromolecular chitosan solution. In addition, a two-layer coating, the first of a macromolecular chitosan solution, and the second of a dispersion of the embedded extracts in chitosan particles, was applied to the PLA films as a novel approach. The success of the coatings was monitored by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and the wettability was evaluated by contact angle measurements. Scanning electron microscopy SEM tracked the morphology and homogeneity of the coating. Antioxidation was studied by DPPH and ABTS spectrophotometric tests, and microbiological analysis of the films was performed according to the ISO 22196 Standard. Desorption of the coating from the PLA was monitored by reducing the elemental composition of the films themselves. The successful functionalization of PLA was demonstrated, while the XPS and ATR-FTIR analyses clearly showed the peaks of elemental composition of the extracts and chitosan on the PLA surface. Moreover, in all cases, the contact angle of the bilayer coatings decreased by more than 35-60% and contributed to the anti-fogging properties. The desorption experiments, due to decrease in the concentration of the specific typical element (nitrogen), indicated some migration of substances from the PLA's surface. The newly developed films also exhibited antioxidant properties, with antioxidant ABTS efficiencies ranging from 83.5 to 100% and a quite high inhibition of Gram-positive Staphylococcus aureus bacteria, averaging over 95%. The current functionalization of PLA simultaneously confers antifogging, antioxidant, and antimicrobial properties and drives the development of a biodegradable and environmentally friendly composite material using green chemistry principles.

Assessing the colloidal stability of copper doped ZIF-8 in water and serum

Colloidal formulations to treat cardiovascular conditions are urgently needed since diseases like atherosclerosis are a major societal burden and agonizing for affected individuals. Copper ions and zinc ions as well as correctly dosed nitric oxide (NO) have long been known to alleviate these pathologies. Herein, we present strategies for size-controlled crystallization of copper-doped Zeolitic Imidazolate Framework 8 (ZIF-8). The colloidal stability and structural integrity of copper-doped ZIF-8 was assessed in water and blood serum. Key findings of the present study include that structural integrity of colloidal copper doped ZIF-8 in blood serum is maintained over several days, while disintegration occurs more quickly in water. Further, we confirmed the known ability of copper-doped ZIF-8 micro-particles to convert blood borne s-nitrosothiols into nitric oxide for the presented colloidal formulations. Nitric Oxide conversion was more moderate and sustained in colloidal copper-doped ZIF-8 formulations compared to free copper ions in solution, which is crucial for many biomedical applications. Another key finding of the present study is that the onset of rapid structural disintegration of copper-doped ZIF-8 occurs at pH 5.5, which is a common physiological pH regime of atherosclerotic plaques. Colloidal particles are known to accumulate in atherosclerotic plaques and the presented system may be a valuable addition to the emerging field of nanomedicines for atherosclerosis treatment. The present study has evaluated the colloidal stability and structural integrity, establishing required material characteristics needed for biological evaluation of the material in future dedicated studies.

Advanced formulations and nanotechnology-based approaches for pulmonary delivery of sildenafil: A scoping review.

Oral sildenafil (SDF) is used to treat pulmonary arterial hypertension (PAH), and its bioavailability is approximately 40%. Several formulations of nano and microparticles (for pulmonary delivery) are being developed because it is possible to improve characteristics such as release time, bioavailability, dose, frequency, and even directly target the drug to the lungs. This review summarizes the latest SDF drug delivery systems for PAH and explains challenges related to the development, the preclinical, and the clinical studies. A scoping review was conducted by searching electronic databases including PubMed, Scopus, and Web of Science to identify studies published between 2001 and 2021. From 300 articles found, 31 met the inclusion criteria. This review identified colloidal formulations such as polymeric, lipid, and metal-organic framework nanoparticles. Strategies were determined to reach the deep airways such as polymeric microparticles, large porous microparticles, nanocomposites, and nano in microparticles. Finally, aspects related to toxicological, pharmacokinetics, and gaps in information for potential use in humans were discussed. SDF formulations are significant candidates for the treatment of PAH by inhalation. In summation, future preclinical studies are still required in large animals, as there is no particular formulation yet submitted to clinical studies.

Basal Surface Hybridization of Group V Layered Transition Metal Dichalcogenides

Efficient, scalable, and tailorable surface hybridization of layered transition metal dichalcogenides (LTMDs) is crucial to optimize performance and enable reproducible, bulk manufacturing technologies (spray coating, inkjet printing, slot-dye coating, etc.) for optoelectronic, energy storage, and sensing applications. Group V LTMDs (NbX2, TaX2, VX2, where X = S, Se, Te) provide unique opportunities due to their superconductive and paramagnetic properties; however, their hydrolytic instability challenges colloidal formulation into composites and devices. Herein, we demonstrate basal surface hybridization of Group V LTMDs via anhydrous Lewis acid/base pair chemistry (amines, phosphines). The developed chemistries allow for robust, stable colloidal dispersions in aprotic solvents. Stoichiometric hybridization provides tunable optoelectronic properties and resistance to hydrolysis. First-principles calculations indicate electron donation from the ligand, implying the possibility of saturation of the frontier d-orbitals where the metallic band structure would collapse into a semiconducting manifold. This class of hybridization chemistries provides insights into derivatization of LTMDs based on their electronic valency.

Microfluidics investigation of the effect of bulk nanobubbles on surfactant-stabilised foams

In aqueous foams, the bubble size usually spans from tens of microns to centimetres. However, it is possible to create much smaller and stable bubbles in solutions: nanobubbles have diameters well below a micron. Many issues are still pending on nanobubbles, especially regarding their stability. Here, we address if and how the addition of nanobubbles may change the interfacial and foaming properties of surfactant solutions. Using a first microfluidic device, nanobubbles are formed within the aqueous surfactant solutions (SDS and Triton X-100 at different concentrations). A second microfluidic device then generates foams from these solutions. Additionally, we report systematic results on the interfacial and bulk properties of such solutions. Finally, we show that nanobubbles have some effects on almost all the measured quantities; however, the most striking one is enhancing the foaming of the solutions with an initial poor foamability. These measurements provide us with a comprehensive set of new results allowing us to draw a first multi-scale picture of how far nanobubbles could potentially act as foam boosters and stabilizers or be implemented in colloidal formulations. Yet, more investigations are required to unravel the mechanisms leading to our results.