Low Irritation Research Articles

Bioactive glass suspension hydrogel promotes wound healing by modulating fibroblasts

The irritation and adhesion of wound healing biomaterials to wet wounds should be addressed for achieving effective wound healing. In this study, a stable multifunctional hydrogels (BGs/HA suspension gels) were prepared using superfine powder of bioactive glasses (BGs), the biocompatible materials hyaluronic acid (HA) and carbomer940, which had good adhesion and low irritation properties for use in moist complex wounds. The average particle size of BGs/HA suspension gels was 13.11 ± 0.29μm, and the BG content was 15.8 ± 0.2% (m m-1). The results of cell proliferation, cell migration, and immunofluorescence staining experiments showed that in the initial stage of wound healing, the ionic extract of BGs formulations promoted the proliferation and migration of L929 cells and induced the secretion ofα-SMA and collagen I. In the final stage of repair, the ionic extract of the BGs formulation regulated the differentiation of fibroblast, which contributed to the reduction of pathological scar formation.In vivoexperiments showed that the wound healing rate of BGs/HA suspension gels group exceeded higher than that of the conventional BGs superfine powder group. Although BGs/HA suspension gels were comparable to its commercially available counterpart (Dermlin paste) in promoting wound healing, it addressed the problem of localized irritation caused by the high pH and low adhesion of BGs products. This study confirmed the specific regulatory effect of BGs/HA suspension gels on L929 cells, which provided a reference for the clinical application of BGs in wound dressing.

Self-Healing Hydrogel Resulting from the Noncovalent Interaction between Ropivacaine and Low-Molecular-Weight Gelator Sodium Deoxycholate Achieves Stable and Endurable Local Analgesia in Vivo.

Regional analgesia based on the local anesthetic ropivacaine plays a crucial role in postoperative pain management and recovery; however, the short duration of analgesia limits its clinical potential. Various drug delivery systems such as microparticles and lipid carriers have been used to prolong the analgesic effect, yet most of them are prone to abrupt release from the site of administration or have poor analgesic effects of less than 48 h, which fail to meet the needs of postoperative analgesia. In this study, a low-molecular-weight gelator sodium deoxycholate-based hydrogel loaded with ropivacaine (DC-ROP gel) was designed for long-acting analgesia. The noncovalent interaction between ropivacaine and sodium deoxycholate helps to improve the stability and sustained release performance of the gel. This internal drug-binding hydrogel also avoids experiencing the burst release effect commonly seen in polymer hydrogels previously reported for the slow release of local anesthetics. DC-ROP gel exhibited the dual advantages of self-healing after compression and long-term controlled release. In mice with inflammatory pain, DC-ROP gel achieved peripheral nerve block for more than 1 week after a single injection. Histological and blood biochemical analyses confirmed that the DC-ROP gel did not produce systemic toxicity, and cytotoxicity experiments demonstrated that the DC-ROP gel resulted in low irritation. These results suggest that DC-ROP gel provides a promising strategy for local anesthetics in long-term postoperative pain management, broadening the potential of bile salt-based low-molecular-weight hydrogels for drug delivery.

Novel Thermus thermophilus and Bacillus subtilis mixed-culture ferment extract provides potent skin benefits invitro and protects skin from aging.

Skin aging is one of the most abundant aging-related disorders that can be accelerated by excessive exposure to ultraviolet irradiation. Topically applied fermented skincare ingredients have gained mounting attentions due to their high concentration of various skin nourishing nutrients and bioactive components and low skin irritation potency. In the present study, we aim to fully demonstrate the skin-related benefits of a novel extract of Thermus thermophilus and Bacillus subtilis mixed-culture ferment (TBFE). TBFE was prepared through an innovative mixed-culture fermentation process. The contents of nutrients and bioactive ingredients were quantified by different methods accordingly. Both invitro tests and randomized controlled human trial were utilized to further demonstrate multifaceted beneficial effects on human skin, as well as the potential mechanisms. Our results showed that TBFE upregulated the expression of type IV collagen, elastin, aquaporin-3, and dermal-epidermal junction markers, while inhibited production of melanin, in different skin cell models. Moreover, TBFE inhibited the generation of reactive oxygen species and pro-inflammatory mediators induced by ultraviolet irradiation in normal human keratinocytes, while stimulated autophagy in senescent keratinocytes. Results from clinical studies confirmed those invitro findings, demonstrating that TBFE at 5% and 20% concentration provides anti-aging properties in subjects with sensitive skin, in terms of improving wrinkles, moisturization, and skin lightening. In summary, we demonstrate that a novel mixed-culture ferment extract has promising anti-aging effects, which may be attributed to anti-oxidation, anti-inflammation, and promotion of autophagy in skin cells.

Wrinkle Reduction Using Tetrapeptide-68 Contained in an O/W Formulation: A Randomized Double-Blind Placebo-Controlled Study.

Peptides, composed of 2-50 amino acids, have gained attention in anti-aging treatments due to their high safety, low irritation, and cost-effective production. This study aimed to evaluate the anti-wrinkle efficacy of Tetrapeptide-68, derived from the skin structural protein Loricrin, on periorbital wrinkles in women aged 30-65 years. A 12-week, double-blind, randomized controlled trial was conducted with 25 participants who applied the Tetrapeptide-68 (100 ppm) O/W formulation around the eyes. Skin physiological parameters were assessed at baseline, 4, 8, and 12 weeks. Participants also completed efficacy and usability questionnaires. Significant improvements in wrinkle reduction were observed with Tetrapeptide-68 cream treatment, as measured by various skin roughness parameters and 3D imaging analysis. Participants reported positive changes in skin texture and moisture levels, with no adverse reactions noted. Tetrapeptide-68 cream demonstrates promising anti-wrinkle effects, highlighting its potential as an effective ingredient in anti-aging skincare formulations. Further studies are recommended to explore its long-term benefits and underlying mechanisms.

Enhancement of Exfoliating Effects through the Novel Cosmetic Ingredient Mandelic acid_Carnitine Ion-Pairing Complex.

This study aimed to develop a novel exfoliating material with high efficacy and low irritation by synthesizing the Mandelic acid_Carnitine ion pairing complex (M_C complex) and evaluating its exfoliating properties. Additionally, the study assessed the skin improvement effects of the M_C complex through clinical evaluations. The M_C complex was synthesized in a 1:1 molar ratio of Mandelic acid and Carnitine. Structural characterization was performed using dynamic light scattering and Fourier-transform infrared spectroscopy. Exfoliating efficacy was evaluated on porcine skin, and clinical assessments were conducted on human subjects to measure various skin improvement parameters. The formation of the M_C complex was confirmed through particle size analysis, zeta-potential measurements, and FT-IR spectroscopy. The M_C complex demonstrated superior exfoliating efficacy compared to Mandelic acid alone, especially at pH 4.5. Clinical evaluations showed significant improvements in blackheads, whiteheads, pore volume, depth, density, count, and affected area, as well as skin texture. No adverse reactions were observed. The M_C complex exhibits high exfoliating efficacy and minimal irritation, making it a promising cosmetic ingredient for improving skin health. These findings support its potential as a low-irritation exfoliating material under mildly acidic conditions, contributing to overall skin health enhancement.

Sustainable production of multifunctional melanin-like amino acid surfactant by conjugating o-quinone building block from natural polyphenols

Surfactants occupy a prominent place in the domestic and industrial fields. Amino acid surfactants have attracted attention as alternatives to petrochemical-based surfactants owing to their good biocompatibility and biodegradability. Conventional amino acid surfactants with structures having only acyl linkages lack multifunctionality. Therefore, novel amino acid surfactants must be developed to achieve this feature. Inspired by melanogenesis, the biomimetic synthesis of melanin-like amino acid surfactants with structures similar to that of melanin was conceived. Natural polyphenols with catechol moieties serve as building blocks for hydrophobic moieties. As a proof-of-concept, caffeic acid phenethyl ester was oxidized to o-quinone using periodate resin. Melanin-like amino acid surfactants were synthesized by conjugating amino acids to o-quinones via Michael addition and Schiff base reactions. The structure was confirmed by mass spectrometry. Melanin-like amino acid surfactants have outstanding surface activity with a low critical micelle concentration and excellent capacity for foaming, emulsifying, dispersing, wetting, and solubilizing. Melanin-like amino acid surfactants exhibit low skin irritation, as well as high tolerance to ions and pH. The utilization of polyphenols introduces multifunctionality, affording antioxidant, antibacterial and whitening activities. This study proposes a modular strategy for fabricating new and multifunctional amino acid surfactants that mimic melanin by simply replacing the o-quinone building block. This biomimetic synthesis route is a sustainable process for the green production of amino acid surfactants. This new generation of amino acid surfactants will contribute to meeting the increasing demand for multifunctional surfactants in both academia and industry.

Potential of Bioactive Protein and Protein Hydrolysate from Apis mellifera Larvae as Cosmeceutical Active Ingredients for Anti-Skin Aging.

This study aimed to extract bioactive proteins and protein hydrolysates from Apis mellifera larvae and assess their potential application in cosmetics as well as their irritation properties. The larvae were defatted and extracted using various mediums, including DI water, along with 0.5 M aqueous solutions of sodium hydroxide, ascorbic acid, citric acid, and hydrochloric acid. Subsequently, the crude proteins were hydrolyzed using the Alcalase® enzyme. All extracts underwent testing for antioxidant activities via the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and Griess assays. Anti-aging properties were evaluated in terms of anti-collagenase and anti-hyaluronidase effects. Irritation potential was assessed using the hen's egg chorioallantoic membrane (HET-CAM) test. The results revealed that the sodium hydroxide extraction showed promising outcomes in terms of yield, protein content, and effectiveness in inhibiting hyaluronidase, with the highest inhibition at 78.1 ± 1.5%, comparable to that of oleanolic acid. Conversely, crude protein extracted with ascorbic acid and its hydrolysate showed notable antioxidant and collagenase-inhibitory activities. Remarkably, their anti-collagenase effects were comparable to those of ascorbic acid and lysine. Additionally, it demonstrated safety upon testing with the CAM. In conclusion, the findings provided valuable insights into the utilization of A. mellifera larval proteins as active ingredients with a wide range of cosmeceutical applications, particularly due to their antioxidant, anti-aging, and low irritation properties, which hold significant promise for anti-skin wrinkles.

Protium spruceanum Extract Enhances Mupirocin Activity When Combined with Nanoemulsion-Based Hydrogel: A Multi-Target Strategy for Treating Skin and Soft Tissue Infections.

The treatment of skin and soft tissue infections (SSTIs) can be challenging due to bacterial resistance, particularly from strains like MRSA and biofilm formation. However, combining conventional antibiotics with natural products shows promise in treating SSTIs. The objective of this study is to develop a nanoemulsion-based hydrogel containing Protium spruceanum extract and mupirocin and evaluate its potential for the treatment of SSTIs. The nanoemulsion was obtained by phase inversion and subsequently characterized. The antibacterial activity was evaluated in vitro against S. aureus MRSA, including the synergism of the combination, changes in membrane permeability using flow cytometry, and the anti-biofilm effect. In addition, the irritative potential was evaluated by the HET-CAM assay. The combination exhibited synergistic antibacterial activity against S. aureus and MRSA due to the extract enhancing membrane permeability. The hydrogel demonstrated suitable physicochemical properties, inhibited biofilm formation, and exhibited low irritation. The formulation was nanometric (176.0 ± 1.656 nm) and monodisperse (polydispersity index 0.286 ± 0.011). It exhibited a controlled release profile at 48 h and high encapsulation efficacy (94.29 ± 4.54% for quercitrin and 94.20 ± 5.44% for mupirocin). Therefore, these findings suggest that the hydrogel developed could be a safe and effective option for treating SSTIs.

Antiadhesive, antibacterial, and anti-inflammatory sandwich-structured ZIF8-containing gauze for enhanced wound healing

Medical gauze is commonly used in clinical practice due to its low irritation, flexibility, and permeability. However, conventional gauze frequently lacks adequate antibacterial and anti-adhesion properties, and gauze that is only superhydrophobic or antibacterial seldom meets the full requirements of infected wound treatment. In this work, we report optimal air permeability, water and blood absorption, and biocompatibility, and effective antibacterial properties of a sandwich-structured gauze composed of a superhydrophobic outer layer, a zeolite imidazolate framework-8 (ZIF8) interlayer, and a superhydrophobic inner layer containing blood-drainage channels (denoted SZS gauze). Three ZIF8 interlayers, ZIF8-1, ZIF8-2, and ZIF8-3, were prepared by soaking medical gauze samples in a mixed solution of 50 mL methanol, 50 mL ethanol, and 0.25, 0.50, or 1.00 g zinc acetate before flat drying, and had Zn content of 0.28, 0.34, and 0.46at.%, respectively, and their corresponding SZS gauze samples are denoted SZS-1, SZS-2, and SZS-3, respectively. Among all gauze samples, the SZS-2 showed the highest cytocompatibility toward L929 cells and effective in vitro antibacterial ability against E.coli and S.aureus. In a rat subcutaneous inflammation model, the SZS-2 showed complete biosafety and the best antibacterial and anti-inflammatory effects against E.coli and S.aureus mixed bacteria among all gauze samples including standard medical gauze and a sandwich-structured gauze with a blank interlayer between two superhydrophobic layers. These findings indicate that the SZS-2 gauze is a promising candidate for advanced wound care, particularly in the management of infected wounds.

Controlled release of vitamin A palmitate from crosslinked cyclodextrin organic framework for dry eye disease therapy

Controlled release drug delivery systems of eye drops are a promising ophthalmic therapy with advantages of good patient compliance and low irritation. However, the lack of a suitable drug carrier for ophthalmic use limits the development of the aforementioned system. Herein, the crosslinked cyclodextrin organic framework (COF) with a cubic porous structure and a uniform particle size was synthesized and applied to solidify vitamin A palmitate (VAP) by using the solvent-free method. The VAP@COF suspension eye drops were formulated by screening co-solvents, suspending agents, and stabilizing agents to achieve a homogeneous state and improve stability. According to the in vitro release study, the VAP@COF suspension exhibited a controlled release of VAP within 12 h. Both the ex vivo corneal contact angle and in vivo fluorescence tracking indicated that the VAP@COF suspension prolonged the VAP residence time on the ocular surface. This suspension accelerated the recovery of the dry eye disease (DED) model in New Zealand rabbits. Furthermore, the suspension was non-cytotoxic to human corneal epithelial cells and non-irritation to rabbit eyes. In summary, the particulate COF is an eye-acceptable novel carrier that sustains release and prolongs the VAP residence time on the ocular surface for DED treatment.

Valorisation of Raspberry Seeds in Cosmetic Industry-Green Solutions.

The fruit processing industry generates large quantities of by-products well known to be rich in bioactive compounds with numerous nutritional properties and beneficial effects for human health. We developed a strategy to valorise raspberry seeds and obtain valuable ingredients with potential application in cosmetic skincare formulas. Cold press extraction technology was applied to extract oil, and the remaining defatted raspberry seed cake was treated with three proline based deep eutectic solvents (DES) to extract polyphenols. The most potent was proline/citric acid extract, with free and total ellagic acid content (52.4 mg/L and 86.4 mg/L), total phenolic content (TPC, 550.1 mg GAE/L) and radical scavenging activity (RSA, 4742.7 mmol TE/L). After the direct mixing of the extract and after encapsulation with starch as a carrier, the skincare emulsion and microemulsion were characterised by irritation potential (Zein test), transepidermal water loss (TEWL), red blood cell (RBC), and DPPH antioxidant test. The resulting preparations were of improved quality in comparison to the control hand cream, with a low skin irritation effect, lower TEWL, and higher antioxidant potential. This work complies with circular economy principles and green technology standards, and represents the efficient model on how to reuse natural resources through waste minimization.

Frequency-encoded eye tracking smart contact lens for human–machine interaction

Eye tracking techniques enable high-efficient, natural, and effortless human-machine interaction by detecting users’ eye movements and decoding their attention and intentions. Here, a miniature, imperceptible, and biocompatible smart contact lens is proposed for in situ eye tracking and wireless eye-machine interaction. Employing the frequency encoding strategy, the chip-free and battery-free lens successes in detecting eye movement and closure. Using a time-sequential eye tracking algorithm, the lens has a great angular accuracy of <0.5°, which is even less than the vision range of central fovea. Multiple eye-machine interaction applications, such as eye-drawing, Gluttonous Snake game, web interaction, pan-tilt-zoom camera control, and robot vehicle control, are demonstrated on the eye movement model and in vivo rabbit. Furthermore, comprehensive biocompatibility tests are implemented, demonstrating low cytotoxicity and low eye irritation. Thus, the contact lens is expected to enrich approaches of eye tracking techniques and promote the development of human-machine interaction technology.

Formulation and Evaluation of Lipid-based Nanoformulation of Itraconazole

The powdered form of itraconazole is white, flavorless, and stable, but it dissolves slowly in water. In comparison to palmitic acid, stearic acid has a stronger affinity (2.57), as shown by the partition coefficient test. UV-visible spectra analysis reveals critical compound insights. Fourier-transform infrared (FTIR) identifies significant peaks in itraconazole and related compounds. tween 80 is selected for solid lipid nanoparticles (SLN) based on their appearance. Optimization using 0.5% w/v tween 80 yielded better particle capture. Thermal analyses display distinctive characteristics of itraconazole, palmitic acid, and polyvinyl alcohol. Viscosity studies mirror tear film behavior. Transmission electron microscope (TEM) images demonstrate SLN’s potential ocular application without irritation. Antifungal studies exhibit effective inhibition of Candida albicans and Aspergillus flavus growth. SN-7 reveals strong encapsulation efficiency, mean vesicle size, and sustained drug release over 12 hours. Pharmacokinetic studies shed light on SLNs’ influence on drug absorption and distribution, indicative of potential in drug delivery systems. These findings offer promising prospects in formulating enhanced drug delivery mechanisms and understanding their impact on drug pharmacokinetics. High-performance liquid chromatography (HPLC) analysis confirmed SN-7’s singular peak at 6.59 minutes. Both formulations showcased skin penetration and stability over three months under varied conditions. Skin irritation tests on rats indicated minimal reactions, affirming low irritancy, which is crucial for patient comfort and acceptance in topical drug delivery. These assessments ensure safety and effectiveness in treating fungal infections.

Synthesis and interface behaviors of amino acid surfactants with naturally derived branched hydrophobic chains

Amino acid surfactants play a crucial role in many personal care products and pharmaceuticals. Their significance arises from their unique characteristics, including diverse molecular structures, low skin irritation, and excellent biodegradability. The structure of amino acid surfactants, particularly the structure of their hydrophobic chains, plays a pivotal role in determining their interfacial properties. It is proposed that the steric hindrance effect stemming from the presence of branched hydrophobic chains can exhibit a profound influence on both the interfacial adsorption behavior and the overall performance of amino acid surfactants. We synthesized a range of novel amino acid surfactants featuring varying lengths of branched chains, derived from natural terpenoid alcohols. Several characterization techniques, including surface tension measurements, dynamic light scattering, foam volume assessments, demulsification time evaluations, and contact angle measurements were used to reveal the substantial influence of branched chains and the chain length on the surfactant performance. The investigation shows how the presence of branched chains influences their interfacial properties, their propensity to form larger aggregates above the critical micelle concentration and the impact of pH on the surfactants performance. Within the examined pH range, surfactants featuring natural branched farnesol chains exhibit critical micelle concentration ranging from approximately 0.8 to 3.8 mM. Those values are significantly lower when compared to surfactants possessing similar length of linear chains. Simultaneously, the conversion of linear hydrophobic chains into branched chains enhances the foam stability promoted by the surfactants by approximately 10 %. These findings emphasize the collective impact of hydrophobic interactions and steric hindrance of the hydrophobic chains on surfactant surface packing. The distinctive interfacial behavior exhibited by branched surfactants shows great potential in establishing a theoretical foundation for formulation research in the development of highly efficient detergents and premium cosmetics.

Safety-in-use test of facial cosmetic products on normal and self-assessed sensitive skin subjects.

Safety-in-use (SIU) studies are commonly used by the cosmetic Industry to confirm the skin and ocular compatibility of cosmetic products under realistic in-use conditions. There are only limited case studies published about the design, outcome and interpretation of product SIU studies. A series of SIU case studies is presented to demonstrate the considerations in study design and how the methodology can help in supporting skin and ocular safety profile of facial cosmetic products within a population of different ethnicities with normal and self-perceived sensitive skin. In a series of four single-blinded SIU studies, more than 250 female study subjects of different ethnicities and with normal and self-assessed sensitive skin were asked to use different facial cosmetic products including lotions, essences and cleansers according to the instructed usage conditions of these products. Each study was specifically designed according to product usage scenarios and target consumer groups. The primary measures of safety were based on dermal evaluations by a dermatologist for erythema and dryness/scaling and by an ophthalmologist for any visible signs of an ocular condition on eyelids, conjunctivae and cornea. The study subjects were also asked for any self-perceived skin or eye reactions. Dermal and ocular irritation potential of the products under realistic product usage conditions was evaluated according to the measures. Across all studies, objectively and self-assessed mean scores for skin and eye effects did not indicate any cumulative response of the investigated products over the study period. As a suitable tool for assessing and establishing the skin and eye compatibility of facial cosmetic products, SIU studies can be designed according to specific consumer groups, skin types and product usage scenarios to better predict realistic in-use conditions. It can demonstrate the safe use of the investigated products for people of different ethnicities, skin types and with normal or self-assessed sensitive skin, single product use or regimen use. The test results are consistent with the inherently low irritation potential of the products.

Design and Evaluation of Tretinoin Fatty Acid Vesicles for the Topical Treatment of Psoriasis

The goal of the current study was to explore the potential benefits of Tretinoin (Tre) fatty acid vesicles (Tre-FAV) as a prospective antipsoriatic topical delivery system. This promising system can counteract the drug challenges in terms of its extremely low aqueous solubility, instability, skin irritation, and serious systemic adverse effects. Tre-loaded fatty acid vesicles were successfully developed and entirely characterised. The selected formulation was investigated for in vitro release, ex vivo skin retention and psoriasis efficacy studies. The characterisation results of Tre-FAV showed it has a globular shape with a particle size of 126.37 ± 1.290 nm (0.188 ± 0.019 PDI). The entrapment efficiency and zeta potential were discovered to be 84.26 ± 0.816% and −28.9 ± 1.92 mV, respectively. Encapsulation of the drug in the fatty acid vesicles was also strengthened by differential scanning calorimetric and powder FTIR diffraction studies. In vitro release results showed that Tre-FAV significantly increased skin absorption and retention in comparison to the Tre solution. The topical application of Tre-FAV to a mouse model confirmed that it has superior in vivo antipsoriatic properties in terms of well-demarcated papules, erythema and reduced epidermal thickness in comparison to other treatments. The weight of the spleen and the levels of the cytokines IL-17 and IL-6 decreased after treatment. In conclusion, FAV dramatically increased the water solubility and skin permeability of Tre and its anti-psoriasis activity.

Synthesis and Performance of Biobased Surfactants Prepared by the One-Pot Reductive Amination of l-Arabinose and d-Galacturonic Acid.

Herein, we report a method for the synthesis of biobased surfactants derived from sugar beet pulp (SBP) monosaccharides, l-Ara and d-GalA. The surfactants were prepared via one-pot reductive amination, allowing the introduction of different alkyl chain lengths and methyl modifications. Optimal reaction conditions were established to achieve high yields and easy purification. The synthesized surfactants including the tertiary amines exhibited desirable properties, including solubility, foamability, and reduction of surface tension. Notably, the anionic surfactants derived from d-GalA demonstrated better solubility and foam performance compared to those derived from l-Ara. In addition, these surfactants exhibited surface tension and critical micelle concentration (CMC) comparable to those of the commercial surfactant sodium lauryl ether sulfate (SLES). Furthermore, the biodegradable surfactant GalA1.8 displayed excellent emulsifying properties and low skin irritation potential. On the l-Ara surfactant with a short chain, Ara1.6 has potential as a hydrotrope. These findings suggest that biobased surfactants derived from SBP monosaccharides have promising applications in various industries, including pharmaceuticals, cosmetics, detergents, and chemicals.

Preparation, Biological Activities, and Application of Plant Polysaccharide Iron Complexes: A Review

AbstractIron is an essential trace element in the human body. Iron deficiency can lead to iron deficiency anemia (IDA) and induce various diseases. Hence, it is urgent to find an iron supplement with minimal side effects and good iron supplementation effect. Natural polysaccharides from plants have various biological activities such as antioxidant, hypoglycemic, immunomodulatory, etc. Increasing research has shown that polysaccharides modified with iron can enhance their biological activities. Among them, polysaccharide iron complex (PIC) has significant anti‐anemia activity. With the powerfully development of PIC, increasing research has found that PIC showed some advantages, including good water solubility, high bioavailability, low gastrointestinal irritation, and high iron content. Therefore, PIC has received widespread attention. Currently, PIC is widely used in various fields such as agriculture, animal husbandry, and clinical treatment. However, there are limited reports on the preparation, biological activities, and applications of PIC. This paper systematically reviews the preparation methods, iron content determination methods, biological activities, and applications of PIC. The results provide important references for the deep development and utilization of PIC.

Classification of antineoplastic drug-induced tissue damage: a Consensus of the Spanish Oncology Pharmacy Group

ObjectiveTo reach at an expert consensus, using the Delphi method, for classifying the tissue-damaging potential of antineoplastic drugs, in order to facilitate the decision-making process in the event of extravasations. MethodThe panel of expert evaluators was made up of seven pharmacists belonging to the working group on extravasations. Other member served as coordinator. The likelihood of tissue damage was reviewed on the basis of eight reference documents. Four categories of drugs were established: vesicant (V); high risk irritant (HRI); low risk irritant (LRI) and non-irritant (NI). Two rounds of surveys were performed. The drugs with an agreement of less than 70% after the two rounds were discussed non-anonymously by the group. For each of the rounds the following was analysed: median of the degree of consensus and the interquartile range (IQR25–75), degree of agreement by tissue damage category, and percentage of antineoplastics reaching a degree of consensus of over 85% and of 100%. Drugs whose classification differed in the various reference documents were assessed separately. SPSS v23.0 statistical software was used. ResultsSeventy-one antineoplastics were evaluated. In the first round, the median for degree of consensus was 100.0% (IQR25–75: 71.4–100.0%). In the second round, the median was 100.0% (IQR25–75: 85.7–100.0%). The percentage of antineoplastics with a consensus of 85.7% or above increased from 66.7% to 85.9% in the second round. For the 30 antineoplastics whose values differed in the reference documents, the degree of agreement increased from 71.4% (IQR25–75: 571–87.7%) to 100.0% (IQR25–75: 85.7–100.0%) in the second round. The percentage of antineoplastics with a consensus of 85.7% or above increased from 40.0% to 76.7%. Four antineoplastics had a degree of agreement of less than 70.0%. The final classification of drugs per category, was: 17 vesicants; 15 HRI; 13 LRI; and 26 NI. The final degree of consensus was 85.7% or above for 90.1% of antineoplastics, and 100.0% for 74.6% of the same. ConclusionsIn this area of scarce evidence and high variability, the Delphi method allows for consensus in classifying tissue damage risk, thus making it easier to reach clinical decisions. In approximately 90% of the antineoplastics, the degree of consensus reached by the expert panel was 85% or above. In 74% of the antineoplastics, it was 100%. This provides solid ground for management decisions.

A study on the preparation conditions of lidocaine microemulsion based on multi-objective genetic algorithm.

Background: Topical lidocaine microemulsion preparations with low toxicity, low irritation, strong transdermal capability and convenient administration are urgently needed. Methods: Box-Behnken design was performed for three preparation conditions of 5% lidocaine microemulsions: mass ratio of the mass ratio of surfactant/(oil phase + surfactant) (X1), the mass ratio of olive oil/(α-linolenic acid + linoleic acid) (X2) and the water content W% (X3). Then, five multi-objective genetic algorithms were used to optimize the three evaluation indices to optimize the effects of lidocaine microemulsion preparations. Finally, the ideal optimization scheme was experimentally verified. Results: Non-dominated Sorting Genetic Algorithm-II was used for 30 random searches. Among these, Scheme 2: X1 = 0.75, X2 = 0.35, X3 = 75%, which resulted in Y1 = 0.17μg/(cm2·s) and Y2 = 0.74mg/cm2; and the Scheme 19: X1 = 0.68, X2 = 1.42, X3 = 75% which resulted in Y1 = 0.14μg/(cm2·s) and Y2 = 0.80mg/cm2, provided the best matches for the objective function requirements. The maximum and average fitness of the method have reached stability after 3 generations of evolution. Experimental verification of the above two schemes showed that there were no statistically significant differences between the measured values of Y1 and Y2 and the predicted values obtained by optimization (p > 0.05) and are close to the target value. Conclusion: Two lidocaine microemulsion preparation protocols were proposed in this study. These preparations resulted in good transdermal performance or long anesthesia duration, respectively.