POLYSORBATE 20

New treatment options are needed for patients with metastatic anti-programmed cell death 1 (PD-1)-resistant melanoma. The final analysis of a phase 1b study evaluating the Toll-like receptor 9 agonist vidutolimod is reported here. This two-part, open-label, multicenter, phase 1b study in adults with metastatic/unresectable anti-PD-1-resistant melanoma evaluated the safety and clinical activity of intratumoral vidutolimod plus systemic pembrolizumab (part 1) or vidutolimod alone (part 2). Two vidutolimod formulations were evaluated with different concentrations of polysorbate (PS20-A, 0.005%-0.01% polysorbate 20; PS20-B, 0.00167% polysorbate 20). Key end points were safety and investigator-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors, version 1.1). A total of 159 patients were treated in part 1 (PS20-A, n = 98; PS20-B, n = 61), and 40 patients were treated in part 2. Any-grade treatment-emergent adverse events (TEAEs) occurred in 100.0% of patients. Grade ≥3 TEAEs occurred in 55.3% (part 1) and 37.5% (part 2) of patients. No treatment-related deaths occurred. Best ORR was 23.5% (95% CI, 15.5%-33.1%; complete response [CR], 7.1%) for vidutolimod PS20-A plus pembrolizumab, 11.5% (95% CI, 4.7%-22.2%; CR, 1.6%) for vidutolimod PS20-B plus pembrolizumab, and 20.0% (95% CI, 9.1%-35.6%) for vidutolimod monotherapy. Median duration of response was 25.2 months with vidutolimod PS20-A plus pembrolizumab, 11.4 months with vidutolimod PS20-B plus pembrolizumab, and 5.6 months with vidutolimod monotherapy. Vidutolimod PS20-A alone or in combination with pembrolizumab had an acceptable safety profile and promising clinical activity in patients with PD-1 blockade-resistant melanoma.

Androgenetic alopecia (AGA) is caused by the impact of dihydrotestosterone (DHT) on hair follicles, leading to progressive hair loss in men and women. In this study, we developed caffeine-loaded hollow mesoporous silica nanoparticles coated with ultradeformable liposomes (ULp-Caf@HMSNs) to enhance caffeine delivery to hair follicles. Caffeine, known to inhibit DHT formation, faces challenges in skin penetration due to its hydrophilic nature. We investigated caffeine encapsulated in liposomes, hollow mesoporous silica nanoparticles (HMSNs), and ultradeformable liposome-coated HMSNs to optimize drug delivery and release. For ultradeformable liposomes (ULs), the amount of polysorbate 20 and polysorbate 80 was varied. TEM images confirmed the mesoporous shell and hollow core structure of HMSNs, with a shell thickness of 25-35 nm and a hollow space of 80-100 nm. SEM and TEM analysis showed particle sizes ranging from 140-160 nm. Thermal stability tests showed that HMSNs coated with ULs exhibited a Td 10 value of 325 °C and 70% residue ash, indicating good thermal stability. Caffeine release experiments indicated that the highest release occurred in caffeine-loaded HMSNs without a liposome coating. In contrast, systems incorporating ULp-Caf@HMSNs exhibited slower release rates, attributable to the dual encapsulation mechanism. Confocal laser scanning microscopy revealed that ULs-coated particles penetrated deeper into the skin than non-liposome particles. MTT assays confirmed the non-cytotoxicity of all HMSN concentrations to human follicle dermal papilla cells (HFDPCs). ULp-Caf@HMSNs promoted better cell viability than pure caffeine or caffeine-loaded HMSNs, highlighting enhanced biocompatibility without increased toxicity. Additionally, ULp-Caf@HMSNs effectively reduced ROS levels in DHT-damaged HFDPCs, suggesting they are promising alternatives to minoxidil for promoting hair follicle growth and reducing hair loss without increasing oxidative stress. This system shows promise for treating AGA.

The objective of this study was to develop novel invaethosomes (I-ETS) and invaflexosomes (I-FXS) to enhance the dermal delivery of clotrimazole (CZ). Twenty model CZ-loaded I-ETS and I-FXS formulations were created according to a face-centered central composite experimental design. CZ-loaded vesicle formulations containing a constant concentration of 0.025% w/v CZ and various amounts of ethanol, d-limonene, and polysorbate 20 as penetration enhancers were prepared using the thin film hydration method. The physicochemical characteristics, skin permeability, and antifungal activity were characterized. The skin permeability of the experimental CZ-loaded I-ETS/I-FXS was significantly higher than that of conventional ethosomes, flexosomes, and the commercial product (1% w/w CZ cream). The mechanism of action was confirmed to be skin penetration of low ethanol base vesicles through the disruption of the skin microstructure. The optimal I-ETS in vitro antifungal activity against C. albicans differed significantly from that of ETS and the commercial cream (control). The response surface methodology predicted by Design Expert ® was helpful in understanding the complicated relationship between the causal factors and the response variables of the 0.025% w/v CZ-loaded I-ETS/I-FXS formulation. Based on the available information, double vesicles seem to be promising versatile carriers for dermal drug delivery of CZ.

Omalizumab can cause hypersensitivity reactions. We herein report the first case of an 18-year-old woman with refractory cough-predominant asthma that correlated with allergic reactions caused by omalizumab and the coronavirus disease 2019 (COVID-19) vaccine. The patient developed angioedema after taking omalizumab. She had previously experienced intense coughing immediately after receiving a COVID-19 vaccine. A skin prick test was positive for polysorbate 20, which was probably the cause of the allergic reactions to omalizumab and the COVID-19 vaccine. Clinicians should check for an allergic reaction, irrespective of its intensity, triggered by polysorbate and be careful when prescribing biologics to patients in order to avoid allergic reactions.

Recent botulinum neurotoxin type A (BoNT/A) formulations have shifted towards the use of polysorbate 20 (PS20) and polysorbate 80 (PS80) as a non-human-derived excipient to enhance product stability. Polysorbates are a distinct class of synthetic non-ionic surfactants with high heterogeneity in chemical structure and properties. Accumulating mechanistic and clinical evidence suggests that they may trigger immunological reactions, including hypersensitivity and immunogenicity. Such risks are largely associated with their susceptibility to degradation via hydrolysis and oxidation, forming reactive byproducts that can interact with proteins and immune pathways. Despite these mechanistic insights, data on the association between polysorbate excipients and observed immune outcomes in practice is relatively sparse and excipient-related immunogenicity and hypersensitivity is often underrecognized in practice. This review provides a summary of polysorbate excipients in BoNT/A formulations, focusing on their chemical properties and degradation pathways, characterizing downstream immune effects and appraising available clinical data of polysorbate-containing BoNT/A formulations. Finally, we discuss potential risk mitigation strategies including process modifications that could prevent degradation, and consideration of alternative excipients, such as human serum albumin, that has been shown to be immunologically inert and has an established safety profile. By integrating chemical, mechanistic, and clinical perspectives, this review seeks to clarify the implications of polysorbate use in BoNT/A formulations and inform both clinical practice and future formulation strategies.

Polysorbate 20 (PS20) is one of the most commonly used non-ionic surfactants in cosmetics, pharmaceuticals and food products. Considered as biocompatible and non-irritating, it is further valued for its solubilising and protein stabilising properties. PS20 is manufactured through a multi-stage reaction of sorbitol with various fatty acids and ethylene oxide, resulting in a complex mixture of components with different molecular weights and polarity. Since variations in the distribution of these components can influence its performance, such as the emulsifying or solubilising efficiency, a detailed understanding of the PS20 composition is of importance. Herein we introduce a combined approach of reversed-phase chromatography with mass detection and automated stochastic modelling that enables the quantitative characterisation of PS20 at the component level. With two straightforward sample preparations and two methods for an ultra-high performance liquid chromatography (UPLC) system coupled to a single quadrupole mass (QDa) detector, this technique ensures efficient data acquisition. Seven PS20 products of different manufacturers, age and qualities were studied using the presented approach. Molar contents and weight percentages were calculated for each of the more than 27'700 components of the PS20, which were fully characterised by i) the substance class (i.e. sorbitan, isosorbide or polyoxyethylene (POE)), ii) the number of esters, iii) the fatty acid combination and iv) the number of OE units. The obtained results allowed not only an accurate prediction of bulk parameters, such as hydroxyl and saponification values, but also a detailed product comparison.

The aim of this work was to investigate the solubility and co-solubilization of fragrance raw materials (FRMs) in sodium dodecyl sulfate (SDS) and polysorbate 20 (P20) surfactant micellar systems, which can advance our knowledge of multi-solute micellar solubilization and fragrance olfactory performance from product matrices containing the surfactants. The transfer of individual FRMs and binary FRM mixtures into micellar phases was quantified by UV-VIS differential spectroscopy and evaluated in terms of the standard Gibbs free energy change and micelle-water partition coefficient. Co-solubilization effects were further evaluated by the deviation ratio. Anionic SDS was found overall to be a more efficient solubilizer than nonionic P20. On an individual basis, micellar solubilization generally increased with solute lipophilicity but was additionally impacted by solute rigidity and steric effects. Micellar solubilization was favoured for more rigid structures and less favoured for FRMs that exhibited larger molecular rotation and steric hindrance. For multi-solute systems, three co-solubilization effects were observed: (i) inhibitive effect in which micellar partitioning of both solutes decreased, (ii) an inverse effect where partitioning of one solute increased while the other decreased and (iii) synergistic effect in which partitioning of both solutes increased. During co-solubilization in P20 micelles, many FRMs competed for solubilization between the polyoxyethylene chains in the outer layer of the micelle, thereby resulting in an inhibitory effect for both solutes. Co-solubilization of FRM binary mixtures in SDS micelles often resulted in a synergistic increase in micellar solubility, possibly due to micellar swelling, thereby facilitating partitioning of additional solutes into the micelle. An inverse effect in which the micellar solubility of one solute increased, while the other decreased was observed in both surfactant systems with varying degrees of partitioning depending on the composition of the FRM mixture. The results of this study provide valuable insights into the impact of FRM composition on multi-solute partitioning behaviour and the impact of surfactant type on co-solubilization in micellar solutions. L'objectif de ce travail est. d'étudier la solubilité micellaire et la co‐solubilisation des matières premières de parfums dans des systèmes de surfactants de dodécylsulfate de sodium (SDS) et de polysorbate 20 (P20), ce qui peut faire progresser nos connaissances sur la solubilisation micellaire multi‐solutés et les performances olfactives des parfums à partir de matrices de produits contenant des surfactants. MÉTHODES: le transfert de matières premières de parfums individuelles et de mélanges binaires de matières premières de parfums dans des phases micellaires a été quantifié par spectroscopie différentielle UV–VIS et évalué en termes de changement d'énergie libre de Gibbs standard et de coefficient de partage micellaire/eau. Les effets de la co‐solubilisation ont été évalués de manière plus approfondie par le rapport de déviation. RÉSULTATS: le SDS anionique s'est. avéré être globalement un solubilisant plus efficace que le P20 non ionique. Sur une base individuelle, la solubilisation micellaire augmentait généralement avec la lipophilie des solutés, mais était également influencée par la rigidité des solutés et les effets stériques. La solubilisation micellaire était favorisée pour les structures plus rigides et moins favorisée pour les matières premières de parfums qui présentaient une rotation moléculaire et un encombrement stérique plus importants. Pour les systèmes multi‐solutés, trois effets de co‐solubilisation ont &

The capacity of micro-organisms to form biofilms is a pervasive trait in the microbial realm. For pathogens, biofilm formation serves as a virulence factor facilitating successful host colonization. Simultaneously, infections stemming from biofilm-forming micro-organisms pose significant treatment challenges due to their heightened resistance to antimicrobial agents. Hence, the quest for active compounds capable of impeding microbial biofilm development stands as a pivotal pursuit in biomedical research. This study presents findings concerning the impact of three surfactants, namely, polysorbate 20 (T20), polysorbate 80 (T80), and sodium dodecyl sulfate (SDS), on the initial stage of biofilm development in both Staphylococcus aureus and Candida dubliniensis. In contrast to previous investigations, we conducted a comparative assessment of the biofilm development capacity of these two taxonomically distant groups, predicated on their shared ability to reduce TTC. The common metabolic trait shared by S. aureus and C. dubliniensis in reducing TTC to formazan facilitated a simultaneous evaluation of biofilm development under the influence of surfactants across both groups. Our results revealed that surfactants could impede the development of biofilms in both species by disrupting the initial cell attachment step. The observed effect was contingent upon the concentration and type of compound, with a higher inhibition observed in culture media supplemented with SDS. At maximum concentrations (5%), T20 and T80 significantly curtailed the formation and viability of S. aureus and C. dubliniensis biofilms. Specifically, T20 inhibited biofilm development by 75.36% in S. aureus and 71.18% in C. dubliniensis , while T80 exhibited a slightly lower inhibitory effect, with values ranging between 66.68% ( C. dubliniensis ) and 65.54% ( S. aureus ) compared to the controls. Incorporating these two non-toxic surfactants into pharmaceutical formulations could potentially enhance the inhibitory efficacy of selected antimicrobial agents, particularly in external topical applications.

Schistosomiasis is a tropical disease transmitted in an aqueous environment by cercariae from the Schistosoma genus. This disease affects 200 million people living in risk areas around the world. The control of schistosomiasis is realized by chemotherapy, wastewater sanitation, health education, and mollusk control using molluscicidal agents. This work evaluates the effects of a nanoemulsion containing essential oil from Myrciaria floribunda leaves as a molluscicidal and cercaricidal agent against Biomphalaria glabrata mollusks and Schistosoma mansoni cercariae. The Myrciaria floribunda essential oil from leaves showed nerolidol, β-selinene, 1,8 cineol, and zonarene as major constituents. The formulation study suggested the F3 formulation as the most promising nanoemulsion with polysorbate 20 and sorbitan monooleate 80 (4:1) with 5% ( w / w ) essential oil as it showed a smaller droplet size of approximately 100 nm with a PDI lower than 0.3 and prominent bluish reflection. Furthermore, this nanoemulsion showed stability after 200 days under refrigeration. The Myrciaria floribunda nanoemulsion showed LC 50 values of 48.11 µg/mL, 29.66 µg/mL, and 47.02 µg/mL in Biomphalaria glabrata embryos, juveniles, and adult mollusks, respectively, after 48 h and 83.88 µg/mL for Schistosoma mansoni cercariae after 2 h. In addition, a survival of 80% was observed in Danio rerio, and the in silico toxicity assay showed lower overall human toxicity potential to the major compounds in the essential oil compared to the reference molluscicide niclosamide. These results suggest that the nanoemulsion of Myrciaria floribunda leaves may be a promising alternative for schistosomiasis control.

Quercetin acts as an antioxidant, anti-inflammatory, wound healing, and anti-aging so quercetin can be used as a topical preparation. However, it has low solubility in water at 0.01 mg/ml at 25 o C. Increasing the solubility of quercetin in water was done by the addition of surfactants. This study compared the solubility of quercetin in Polysorbate 20 (P20) and Polysorbate 80 (P80) in a citrate buffer medium pH 4.5±0.2. The surfactants Polysorbate 80 and Polysorbate 20 differ in their alkyl chain length. Polysorbate 80 has an alkyl chain length of 18, while Polysorbate 20 has an alkyl chain length of 12. The concentrations of surfactant are above, below, and at the critical micelle concentration (CMC) values. The concentrations of quercetin were determined at the maximum wavelength by spectrophotometric method. The results of the quercetin solubility test without surfactant were 3.89±0.59 mg/L. The results of the quercetin solubility test by adding Polysorbate 20 at a concentration of 42.0 ppm; 57.5 ppm; and 73.0 ppm were 3.62±0.72, 4.04±0.23 and 8.35±1.97 mg/L, respectively. While the solubility of quercetin by adding Polysorbate 80 at a concentration of 4.0 ppm, 11.5 ppm, and 19.0 ppm was 11.15±0.72, 11.37±1.23 and 14.17±1.96 mg/L, respectively. The solubility of quercetin is greater after the addition of surfactant Polysorbate 20 only at the concentration above the CMC value and the solubility of quercetin is greater with the addition of surfactant Polysorbate 80 at all concentrations. Surfactant Polysorbate 20 increases the solubility of quercetin in citrate buffer pH 4.5±0.2 only at concentrations above the CMC value of 2.14 times. Polysorbate 80 can increase the solubility of quercetin in citrate buffer pH 4.5±0.2 at concentrations below, at, and above CMC by 2.87, 2.92, and 3.63 times, respectively. Polysorbate 80 can increase the solubility of quercetin in citrate buffer pH 4.5±0.2 higher than Polysorbate 20.

Nonionic lactose fatty acid esters are a class of synthetic biosurfactants with various uses in the food, pharmaceutical, personal care, and cosmetic industries. The objective of this research was the preparation and full characterization of a series of novel metallic encapsulated magnetic core/dendrimer shell composites as catalysts (Co II /Mn II G 2.0 L 1/2 @SCMBNP) and their use in the chemo- and regioselective synthesis of a biosurfactant for the first time. Surface-active properties (such as contact angle (CA), surface tension (SFT), interfacial tension (IFT), critical micelle concentration (CMC), hydrophilic-lipophilic balance (HLB), foamability (FA) & foam stability (FS), emulsion ability (EmA) & emulsion stability (EmS), surface excess ( Γ ) and free energy of adsorption (Δ G ) were also determined for all synthesized biosurfactants. In comparison to other works, these results suggested that the synthesized lactose fatty acid esters have potential application as synthetic emulsifiers featuring surface properties and are comparable with Ryoto sugar ester L-1695 (sucrose laurate) & Tween-20 (polysorbate 20) as industrial emulsifiers. The optimized conditions for biosurfactant syntheses are 8 days at 2 : 1 molar ratio of lactose sugar to lauric acid at 50 °C. Lactose ester as a biosurfactant exhibited a decrease of SFT & IFT and was able to stabilize a 20% soybean O/W emulsion. Furthermore, high conversion & yield, excellent chemo- and regioselectivity, and high operational stability over 5 runs were achieved for Co II /Mn II -G 2.0 L 1/2 @SCMBNP, indicating the suitable efficiency of the catalytic process.

Human serum albumin (HSA) has been widely used as a pharmaceutical excipient in Botulinum toxin serotype A (BoNT/A) products that are indicated for use in therapeutics and cosmetics. However, HSA as a human-derived material has some concerns, such as the potential risk of transmission of infectious agents, an insufficient supply, and difficulty in maintaining a certain quality. For those reasons, newly developed BoNT/A products (CORETOX®, Medytox, Inc., Republic of Korea) contained polysorbate 20, a non-human-derived excipient, to replace the HSA. However, most safety studies of polysorbate 20 have been conducted with non-invasive routes of administration, and thus there are a few studies on the safety of polysorbate 20 when administered intramuscularly. To secure the in vivo safety profile of polysorbate 20, a four-week repeated intramuscular dose toxicity study (0.02, 0.1, and 0.4 mg/kg, one injection every two weeks for a total of three injections) was conducted in 66 Sprague-Dawley (SD) rats. An intradermal irritation study was further conducted with 18 New Zealand White (NZW) rabbits. The toxicological evaluation of HSA (0.06 and 0.12 mg/kg) was also carried out as a comparative substance. Systemic and local toxicities were not observed in any of the SD rats or NZW rabbits based on clinical signs, body weight, hematology, clinical biochemistry, macroscopic findings on necropsy, histopathology of the injection site, and allergic reactions. The current study suggested that intramuscular administration of polysorbate 20 was considered to be safe at a level similar to that of HSA, which has an in vivo safety profile accumulated over the years. This provided the basis for the in vivo safety profile of polysorbate 20 administered intramuscularly and the scientific reliability of the use of polysorbate 20 as an alternative to HSA, which is used as an excipient for various pharmaceuticals in terms of its safety.