The wound healing effect of polycaprolactone-chitosan scaffold coated with a gel containing Zataria multiflora Boiss. volatile oil nanoemulsions.

AIMS: Thymus plant is a very useful herbal medicine with various properties such as anti-inflammatory and antibacterial. Therefore, the properties of this plant have made this drug a suitable candidate for wound healing. In this study, hydroxypropyl methylcellulose (HPMC) gel containing Zataria multiflora volatile oil nanoemulsion (neZM) along with polycaprolactone/chitosan (PCL-CS) nanofibrous scaffold was used, and the effect of three experimental groups on the wound healing process was evaluated. The first group, HPMC gel containing neZM, the second group, PCL-CS nanofibers, and the third group, HPMC gel containing neZM and bandaged with PCL-CS nanofibers (PCL-CS/neZM). Wounds bandaged with common sterile gas were considered as control. METHODS: The nanoemulsion was synthesized by a spontaneous method and loaded into a hydroxypropyl methylcellulose (HPMC) gel. The DLS test investigated the size of these nanoemulsions. A PCL-CS nanofibrous scaffold was also synthesized by electrospinning method then SEM and contact angle tests investigated morphology and hydrophilicity/hydrophobicity of its surface. The animal study was performed on full-thickness skin wounds in rats, and the process of tissue regeneration in the experimental and control groups was evaluated by H&E and Masson's trichrome staining. RESULTS: The results showed that the nanoemulsion has a size of 225±9 nm and has an acceptable dispersion. The PCL-CS nanofibers synthesized by the electrospinning method also show non-beaded smooth fibers and due to the presence of chitosan with hydrophilic properties, have higher surface hydrophobicity than PCL fibers. The wound healing results show that the PCL-CS/neZM group significantly reduced the wound size compared to the other groups on the 7th, 14th, and 21st days. The histological results also show that the PCL-CS/neZM group could significantly reduce the parameters of edema, inflammation, and vascularity and increase the parameters of fibrosis, re-epithelialization, and collagen deposition compared to other groups on day 21. CONCLUSION: The results of this study show that the PCL-CS/neZM treatment can effectively improve wound healing.

An antibacterial and anti-oxidant hydrogel containing hyperbranched poly-l-lysine and tea polyphenols accelerates healing of infected wound.

Both bacteria-infection and excessive inflammation delay the wound healing process and even create non-healing wound, thus it is highly desirable to endow the wound dressing with bactericidal and anti-oxidation properties. Herein an antibacterial and antioxidation hydrogel based on Carbomer 940 (CBM) and hydroxypropyl methyl cellulose (HPMC) loaded with tea polyphenols (TP) and hyperbranched poly-l-lysine (HBPL) was designed and fabricated. The hydrogel killed 99.9 % of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) at 107 CFU mL-1, and showed strong antioxidation against H2O2 and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH) radicals without noticeable cytotoxicity in vitro. The CBM/HPMC/HBPL/TP hydrogel significantly shortened the inflammatory period of the MRSA-infected full-thickness skin wound of rats in vivo, with 2 orders of lower MRSA colonies compared with the blank control, and promoted the wound closure especially at the earlier stage. The inflammation was suppressed and the vascularization was promoted significantly as well, resulting in reduced pro-inflammatory factors including interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), and increased anti-inflammatory factors such as interleukin-4 (IL-4) and interleukin-10 (IL-10).

Study on Improving the Performance of Traditional Medicine Extracts with High Drug Loading Based on Co-spray Drying Technology.

The purpose of this study is to develop modified particles with different structures to improve the flowability and compactibility of Liuwei Dihuang (LWDH) powder using co-spray drying technology, and to investigate the preparation mechanism of modified particles and their modified direct compaction (DC) properties. Moreover, tablets with high drug loading contents were also prepared. Particles were designed using polyvinylpyrrolidone (PVP K30) and hydroxypropyl methylcellulose (HPMC E3) as shell materials, and sodium bicarbonate (NaHCO3) and ammonium bicarbonate (NH4HCO3) as pore-forming agents. The porous particles (Ps), core-shell particles (CPs), and porous core-shell particles (PCPs) were prepared by co-spray drying technology. The key DC properties and texture properties of all the particles were measured and compared. The properties of co-spray drying liquid were also determined and analyzed. According to the results, Ps showed the least improvement in DC properties, followed by CPs, and PCPs showed a significant improvement. The modifier, because of its low surface tension, was wrapped in the outer layer to form a shell, and the pore-forming agent was thermally decomposed to produce pores, forming core-shell, porous, and porous core-shell composite structures. The smooth surface of the shell structure enhances fluidity, while the porous structure allows for greater compaction space, thereby improving DC properties during the compaction process.

Biopolymer based film loaded with Cholecalciferol: A novel technique to enhance nutritional supplement absorbance.

In terms of delivery systems for active compounds, orally disintegrating films are a great option. The initial stage in creating an oral disintegrating film is selecting a film-forming polymer. The basic polymers combination Microcrystalline Cellulose (MCC), which is co-processed with Carboxymethylcellulose Sodium (CMC) and hydroxypropylmethyl cellulose were used to create an oral disintegrating film that contains cholecalciferol (Vitamin D3), a fat-soluble vitamin that aids in the body's absorption of calcium and phosphorus. The goal of the current inquiry was to develop orally disintegrating films of vitamin D3 to improve patient comfort and compliance for pediatric or elderly patients due to its simplicity of administration. Films containing drugs and made of the appropriate plasticizer and chosen polymers demonstrated outstanding film forming and folding endurance. The dissolution test showed that Vitamin D3 has a rapid disintegration property, with the majority of it dissolving in the medium (pH 6.8) in less than two minutes after being inserted. To verify that the films were successfully formed, a variety of procedures including HPLC, FT-IR and microscopic studies were employed. When kept at 40oC with humidity of 75%, the film showed good stability for at least three months.

Enhanced mechanical and functional properties of chitosan/polyvinyl alcohol/hydroxypropyl methylcellulose/alizarin composite film by incorporating cinnamon essential oil and tea polyphenols.

In this study, cinnamon essential oil and tea polyphenols were added to chitosan/ polyvinyl alcohol/ hydroxypropyl methylcellulose/ alizarin composite films to enhance their mechanical and functional properties. Their addition to the composite films enhanced their antibacterial and antioxidant properties and significantly improved its elongation at break (p < 0.05). Cinnamon essential oil reduced the water vapor permeability, water content, and water solubility of composite films and improved their transparency. The composite films with additive exhibited excellent UV-barrier ability and pH responsivity. Fourier Transform infrared spectroscopy and X-Ray Diffraction analyses confirmed hydrogen bond formation between the polymer molecules and additives. The results of Scanning Electron Microscope-Focused Ion Beam revealed improved surface and cross-section morphology of the films, leading to the generation of a cross-linked structure. Thermogravimetric and differential scanning calorimetry analysis indicated enhanced thermal stability of the composite films upon cinnamon essential oil addition. Analysis of storage quality indicators (TBARS value, TVC, and TVB-N) revealed that the composite films could prolong the freshness of surimi. The incorporation of cinnamon essential oil and tea polyphenols into the composite films has demonstrated significant potential as an effective and natural alternative for active food packaging.

Exploration of polymethacrylate and Hypromellose for the development of a non-sulfhydryl ACE inhibitor mucoadhesive system using Box-Behnken design: in-vitro and ex-vivo evaluation.

PURPOSE: To counteract early morning pathology like hypertension a time-dependent release of the drug is required. This study is focused to formulate a pulsatile and mucoadhesive drug delivery system of an ACE inhibitor Perindopril Erbumine. METHOD: Two matrix tablets were punched with Eudragit RSPO, Eudragit RLPO, and HPMC K15M using a 3-3-3 Box-Behnken Design of Response Surface Methodology. Based on the design-optimized formulation P1T3 and P2T8 were coated for a lag time with compression coating of HPMC K4M and a blend of 1:1 ratio of ethylcellulose and carbopol polymer and further encapsulated in a Eudracap™ capsule to provide gastric resistance. RESULT: The in-vitro release data confirmed an initial pause phase of 4.5 h then release of the drug for 5.2 ± 0.3 h to cope with the early morning rush in blood pressure. After that, a gap of 6 h and then sustained release of the drug for 10.5 ± 0.5 h. From the ex-vivo study, mucoadhesive strength was obtained as 55.13 ± 0.03 gm and 56.39 ± 0.02 gm for P1T3 and P2T8 respectively. The lag time for coated tablet P1T3 came to 2.15 ± 0.15 h and for P2T8 11.9 ± 0.10 h proving the coating efficiency of polymers. CONCLUSION: The current study strongly suggests that perindopril Erbumine in association with Eudragit and Hypromellose polymer can open a path for the time-regulated release of the drug for hypertension chronotherapy with less risk of dose dumping.

Synthesis of antibacterial hydroxypropyl methylcellulose and silver nanoparticle biocomposites via solution plasma using silver electrodes.

The biocomposites of hydroxypropyl methylcellulose (HPMC)/silver nanoparticles (AgNPs) were synthesized using the solution plasma process (SPP). HPMC/AgNPs were synthesized in 1-5 % HPMC solutions using silver electrodes. UV-Vis spectroscopy showed a peak near 400 nm and the peak increased as the concentration of HPMC and discharge time increased. FTIR analysis indicated no change in the chemical structure of the HPMC based biocomposites. Spherical shaped AgNPs with size ranges about 2-18 nm and well dispersed in the porous HPMC matrices with fringed edges were observed by TEM and SEM/EDS analyses. The synthesized biocomposites were found to be thermo-stable by TGA analysis. The inhibition zones of bacterial growth formed by the HPMC/AgNPs biocomposites were in the range of 8-14.3 mm; minimal inhibition concentrations, in the range of 10-15 µg·mL-1 for Gram-negative bacteria; 25-30 µg·mL-1 for Gram-positive bacteria. The biocomposites were non-toxic to the HEK293 cells up to 125 µg·mL-1. The results indicated that the synthesis of antibacterial agents in the HPMC matrix using silver electrodes via SPP would be an efficient and safe way for the development of biopolymer based antimicrobials and wound healing biomaterials.

Interaction of polymers with bile salts - Impact on solubilisation and absorption of poorly water-soluble drugs.

Formulating poorly soluble drugs with polymers in the form of solid dispersions has been widely used for improving drug dissolution. Endogenous surface-active species present in the gut, such as bile salts, lecithin and other phospholipids, have been shown to play a key role in facilitating lipids and poorly soluble drugs solubilisation in the gut. In this study, we examined the possible occurrence of interactions between a model bile salt, sodium taurocholate (NaTC), and model spray dried solid dispersions comprising piroxicam and Hydroxypropyl Methylcellulose (HPMC), a commonly used hydrophilic polymer for solid dispersion preparation. Solubility measurements revealed the good solubilisation effect of NaTC on the crystalline drug, which was enhanced by the addition of HPMC, and further boosted by the drug formulation into solid dispersion. The colloidal behaviour of the solid dispersions upon dissolution in biorelevant media, with and without NaTC, revealed the formation of NaTC-HPMC complexes and other mixed colloidal species. Cellular level drug absorption studies obtained using Caco-2 monolayers confirmed that the combination of drug being delivered by solid dispersion and the presence of bile salt and lecithin significantly contributed to the improved drug absorption. Together with the role of NaTC-HPMC complexes in assisting the drug solubilisation, our results also highlight the complex interplay between bile salts, excipients and drug absorption.

Chitosan/xanthan gum-based (Hydroxypropyl methylcellulose-co-2-Acrylamido-2-methylpropane sulfonic acid) interpenetrating hydrogels for controlled release of amorphous solid dispersion of bioactive constituents of Pueraria lobatae.

Pueraria lobatae (Willd) Ohwi is a traditional Chinese medicine used to treat alcohol intoxication, diabetes, cerebrovascular and cardiovascular diseases. Some of its active components include the flavonoids puerarin, daidzin, daidzein, and genistin. The therapeutic efficacy of these agents is hampered by their poor pharmacokinetic profiles (rapid systemic clearance, low oral bioavailability, short half-life) and physicochemical properties (such as poor aqueous solubility and stability). In the current study, chitosan/xanthan gum-based (hydroxypropyl methylcellulose-co-2-acrylamido-2-methylpropane sulfonic acid) hydrogels for the controlled release of Pueraria lobata-solid dispersion (SD) were successfully prepared and characterized. A total of 61 compounds were identified in the Pueraria lobatae-SD using UHPLC-Q-TOF-MS analysis. Hydrogel structure was confirmed by FTIR, XRD, TGA, DSC, and SEM showed a porous structure. Correlations between hydrogels structural properties was also investigated. The hydrogels showed higher swelling after 48 h at pH 1.2 (21.15 %) than pH 7.4 (15.91 %). In vitro drug release study demonstrated that drug release was maximum at pH 1.2 (63 %) compared to pH 7.4 (49 %) after 48 h. The gel fraction of the synthesized hydrogel was increased with the increase in the polymer and crosslinker concentrations. Furthermore, in vitro studies demonstrated that the developed hydrogels possess good antioxidant and antimicrobial properties.

Fabrication, in Vitro, and in Vivo Characterization of Mucoadhesive Berberine-Loaded Blended Wafers for Treatment of Chemotherapy-Induced Oral Mucositis.

This study aims to design and characterize berberine-loaded wafers for the treatment of chemotherapy-induced oral mucositis. Wafers were prepared by lyophilization of hydrogels of various ratios of chitosan (CS)/sodium alginate (SA) as well as CS/hydroxypropyl methylcellulose (HPMC). In vitro release, in vitro mucoadhesion, porosity, and swelling studies were conducted to select the optimized formulations. Moreover, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and mechanical properties studies were also performed for further characterization. The efficacy of optimized berberine-loaded wafers in the treatment of oral mucositis was investigated in a 5FU-induced oral mucositis rat model. F2-CS-SA and F6-CS-HPMC wafers exhibited sustained release profile and excellent mucoadhesion strength. Therefore, these wafers were selected as the optimized formulations. SEM confirmed the porous structure of these wafers and is in agreement with the results of porosity and swelling studies. XRD and FTIR studies indicated that berberine was incorporated into the wafer matrix in the amorphous form. In vivo studies demonstrated that topical application of berberine-loaded optimized wafers reduced significantly the severity of 5FU-induced oral mucositis and decreased the expression of inflammatory markers (TNF-α and IL-1ß). The results of in vitro and in vivo studies revealed that berberine-loaded F2-CS-SA and F6-CS-HPMC wafers can be effective in the treatment of chemotherapy-related oral mucositis.

Effect and Mechanism of Pharmaceutical Excipients on Berberine to Alleviate Ulcerative Colitis via Regulating Gut Microbiota.

BACKGROUND: Various potential effect of drugs on alleviating diseases by regulating intestinal microbiome as well as the pharmaceutical excipients on gut microbiota has been revealed. However, the interaction between them is rarely investigated. METHODS: Histological analysis, immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) analysis, RT-qPCR, and 16S rRNA analysis were utilized to explore the effect mechanism of the five excipients including hydroxypropyl methylcellulose (HPMC) F4M, Eudragit (EU) S100, chitosan (CT), pectin (PT), and rheum officinale polysaccharide (DHP) on berberine (BBR) to cure UC. RESULTS: The combined BBR with PT and DHP group exhibited better therapeutic efficacy of UC with significantly increased colon length, and decreased hematoxylin-eosin (H&E) scores than other groups. Furthermore, the expression of tight junction ZO-1 and occludin in colon tissue were upregulated, and claudin-2 was downregulated. Ultimately, the serum content of tumor necrosis (TNF)-α, interleukin (IL)-1ß, and IL-6 was decreased. Moreover, the combined BBR with PT significantly promoted the restoration of gut microbiota. The relative abundance of Firmicutes and Lactobacillus was significantly increased by the supplement of PT and DHP, and the relative abundance of Proteobacteria was downregulated. CONCLUSIONS: Our study may provide a new perspective that the selection of pharmaceutical excipients could be a crucial factor affecting the drugs' therapeutic efficiency outcome.

Improved direct compression properties of Gardeniae fructus water extract powders via fluid bed-mediated surface engineering.

Direct compression (DC) attracts increasing attention for tablet manufacturing; however, its application in medicinal plant tablets is still extremely limited. In this work, eight kinds of the Gardeniae fructus water extract powder (GF)-based composite particles (CPs) were prepared with different cohesive surface engineering materials, including dextran, inulin, hypromellose, and povidone, alone or in combination with mannitol and colloidal silica. Their physical properties and compacting parameters were characterized comprehensively. All the CPs showed marked improvement in tabletability, which is about 2-4 times higher than that of GF and physical mixtures (PMs). Specifically, the CPs showed a 7.45-26.48 times higher hardness (Ha) value and a 1.26-2.74 times higher cohesiveness (Co) value than PMs. In addition, all the CPs (angle of repose being from 34.27° to 38.46°) showed better flowability than PMs (35.49° to 53.53°) and GF (51.86°). These results demonstrated that (i) fluid-bed coating was not a simple process of superposition and transmission of the physical properties of raw materials; and (ii) all the surface engineering materials studied could improve the DC properties of problematic GF to some degree. As a whole, through the design of fluid-bed coating CPs, qualified tablets with high GF loadings (up to 93%) were produced via DC.

Development of xanthan gum/hydroxypropyl methyl cellulose composite films incorporating tea polyphenol and its application on fresh-cut green bell peppers preservation.

The aim of this work was to develop an edible packaging material with good performance that can be used for fresh-cut vegetables preservation. The xanthan (XG)-hydroxypropyl methylcellulose (HPMC)-tea polyphenols (TP) composite film (XHT) was prepared by adding TP to the composite film-forming solution of XG and HPMC. At optimum TP dosage of 6% (XHT6), the tensile strength and elongation at break were at the maximum. The antioxidant activity and antibacterial properties were also enhanced, demonstrated good inhibitory ability to Staphylococcus aureus. After 8 days, the amount of Vitamin C that was retained by XHT6 was 127.81% and 7.83% higher than unpackaged and XHT0, respectively. Additionally, the MDA content in green peppers were 39.16% and 78.87% higher than that of unpackaged and XHT0, respectively. Practical applications of XHT films in preserving fresh-cut bell peppers had also shown positive results, making it possible as potential food packaging.

Thermosensitive gel based on cellulose derivative for topical delivery of propolis in acne treatment.

Thermosensitive bioadhesive formulations can display increased retention time, skin permeation, and improve the topical therapy of many drugs. Acne is an inflammatory process triggered by several factors like the proliferation of the bacteria Propionibacterium acnes. Aiming for a new alternative treatment with a natural source, propolis displays great potential due to its antibiotic, anti-inflammatory, and healing properties. This study describes the development of bioadhesive thermoresponsive platform with cellulose derivatives and poloxamer 407 for propolis skin delivery. Propolis ethanolic extract (PES) was added to the formulations with sodium carboxymethylcellulose (CMC) or hydroxypropyl methylcellulose (HPMC) and poloxamer 407 (Polox). The formulations were characterized as rheology, bioadhesion, and mechanical analysis. The selected formulations were investigated as in vitro propolis release, cytotoxicity, ex vivo skin permeation by Fourier Transform Infrared Photoacoustic Spectroscopy, and the activity against P. acnes. Formulations showed suitable sol-gel transition temperature, shear-thinning behavior, and texture profile. CMC presence decreased the cohesiveness and adhesiveness of formulations. Polox/HPMC/PES system displayed less cytotoxicity, modified propolis release governed by anomalous transport, skin permeation, and activity against P. acnes. These results indicate important advantages in the topical treatment of acne and suggest a potential formulation for clinical evaluation.

Effect of soybean protein isolate-pectin composite nanoparticles and hydroxypropyl methyl cellulose on the formation, stabilization and lipidolysis of food-grade emulsions.

The formation and stabilization mechanism as well as digestion characteristics of food-grade emulsions prepared by the SPNPs-HPMC mixed systems (a combination of soybean protein isolate-pectin composite nanoparticles (SPNPs) and hydroxypropyl methylcellulose (HPMC)) were investigated. Then, it was found that the SPNPs-HPMC mixed systems could not only enhance the stability of the emulsion, but also make it have a satisfactory lipidolys is efficiency. During the formation and stabilization of the emulsion, HPMC was adsorbed in the early stage of emulsion formation, while SPNPs needed a longer adsorption time. When the HPMC concentration was 0.25-0.5 wt%, HPMC and SPNPs co-adsorbed on the interface. When the HPMC concentration was 1-2 wt%, HPMC and SPNPs competed to adsorb on the interface, of which the adsorption HPMC was dominant. In vitro simulation of digestion, SPNPs were decomposed into substances with lower interfacial activity, and the structure and activity of HPMC were well maintained, which led them to reconstruct a new interface layer. Thus, the size distribution and surface area of the emulsion droplets were retained in a good state for the lipidolysis process. Therefore, the SPNPs-HPMC mixed systems could both enhance the stability of the emulsion and grant it a satisfactory lipidolysis efficiency.

Optimization of Spray-Drying Process Parameters to Study Anti-Sticking Effect of Hydroxypropyl Methyl Cellulose-VLV on Corni fructus Extracts.

To prevent the sticking of Corni fructus extract (CFE) during spray drying, the anti-sticking effects of different excipients were compared. Hydroxypropyl methylcellulose (HPMC)-VLV showed a higher powder yield at a lower dosage (8% of total solids), and a lower solution viscosity, compared with HPMC-E5. Therefore, HPMC-VLV is a more effective excipient for reducing CFE sticking during spray drying. The spray-drying process parameters were optimized by central composite rotatable design/response surface methodology, and spray drying was conducted under the following conditions: Inlet air temperature, 126 °C; atomization pressure, 1.05 bar; pump speed, 7.7 mL/min. Scanning electron microscopy showed that the powder comprised shrunken spherical particles with particle sizes in the range of 2-30 µm. Analysis of dynamic surface tension and chemical elements on the powder surface showed that HPMC-VLV rapidly moved to the droplet surface owing to its surface activity. HPMC covered the droplet surface and reduced surface tension, achieving an anti-sticking effect. In conclusion, HPMC-VLV at a solid content of 8% significantly improved the spray drying and reduced sticking of CFE. The spray-drying process parameters were nonlinearly related to the dry product yield. Graphical Abstract.

Development of fast-dissolving dosage forms of curcuminoids by electrospinning for potential tumor therapy application.

Curcuminoids (CUs) of antitumor and various other potential biological activities have extremely low water solubility therefore special formulation was elaborated. New fast dissolving reconstitution dosage forms of four CUs were prepared as fibrous form of 2-hydroxypropyl-ß-cyclodextin (HP-ß-CD). In the electrospinning process HP-ß-CD could act both as solubilizer and fiber-forming agent. The solubilization efficiency of the CU-HP-ß-CD systems was determined with phase-solubility measurements. The electrospun CUs were amorphous and uniformly distributed in the fibers according to XRD analysis and Raman mappings. The fibrous final products had fast (<5 min) and complete dissolution. In typical iv. infusion reconstitution volume (20 mL) fibers containing 40-80 mg of CU could be dissolved, which is similar to the currently proposed dose (<120 mg/m2). The in vitro cytostatic effect data showed that the antitumor activity of the CU-HP-ß-CD complexes was similar or better compared to the free APIs.

Efficacy of Artificial Tears Based on an Extract of Artemia salina Containing Dinucleotides in a Rabbit Dry Eye Model.

(1) Background: Artemia salina is a brine shrimp containing high concentrations of dinucleotides, molecules with properties for dry eye treatment. For this reason, the purpose of the study was to evaluate the effect of the artificial tears based on an extract of Artemia salina in a rabbit dry eye model. (2) Methods: A prospective and randomized study was carried out. Twenty rabbits were divided into 4 groups (n = 5, each group): healthy rabbits, dry eye rabbits, dry eye rabbits treated with hypromellose (HPMC), and dry eye rabbits treated with Artemia salina. Dry eye was induced by the topical instillation of 0.2% benzalkonium chloride. The measurements were performed before and after the treatment for 5 consecutive days. (3) Results: The topical instillation of artificial tears containing Artemia salina showed beneficial effects on tear secretion, tear break-up time, corneal staining, the density of Goblet cells, heigh of mucin cloud secreted by these cells, and mRNA levels of IL-1ß and MMP9 in conjunctival cells. Compared with the HPMC, there was a statistically significant improvement (p < 0.05) with the Artemia salina in all the variables under study, except for the conjunctival hyperemia, density of Goblet cells, and mRNA levels of IL-6. (4) Conclusions: The potential of artificial tears based on Artemia salina as a secretagogue agent for dry eye treatment was confirmed, opening the door for future clinical trials and studies to extrapolate the findings for dry eye patients.

[Establishment of prediction model for personalized water-paste pills based on classification of traditional Chinese medicine materials].

The purpose of the present study was to investigate the relationship of the classification of traditional Chinese medicine(TCM) materials with the suitable binder concentration and dosage in the preparation of personalized water-paste pills and establish a model for predicting the binder concentration and dosage. Five representative TCM materials were selected, followed by mixture uniform design. The water-paste pills were prepared by extrusion and spheronization with hypromellose E5(HPMC E5) as the binder. The quality of intermediates and final products was evaluated, and the resulting data were subjected to multivariate statistical analysis. The prediction models for binder concentration and dosage were established as follows: binder concentration: Y_1=0.378 6 + 0.570 1X_A + 2.271 2X_B-0.894 5X_C-0.458 2X_D-1.145 4X_E(when Y_1 < 0, 10% HPMC E5 was required; when Y_1 > 0, 20% HPMC E5 was required), with the accuracy reaching up to 100%; binder dosage: Y_2=32.38 + 0.25X_A + 1.85X_B-0.013X_B~2-0.002 5X_C~2(R~2=0.932 6, P < 0.001). The results showed that the binder concentration and dosage were correlated positively with the proportion of fiber material but negatively with the proportions of sugar material and brittle material. Then the validation experiments were conducted with the prediction models and all the prescriptions could be successfully prepared at one time. These demonstrated that following the classification of TCM materials and the calculation of their proportions in the prescription, the established mathematical model could be adopted for predicting the binder concentration and dosage required in the preparation of personalized water-paste pills, which contributed to reducing the pre-formulation research and guiding the actual production of personalized water-paste pills.

Therapeutic Efficacy of Sesquiterpene Farnesol in Treatment of Cutibacterium acnes-Induced Dermal Disorders.

Acne vulgaris is a highly prevalent skin disorder requiring treatment and management by dermatologists. Antibiotics such as clindamycin are commonly used to treat acne vulgaris. However, from both medical and public health perspectives, the development of alternative remedies has become essential due to the increase in antibiotic resistance. Topical therapy is useful as a single or combined treatment for mild and moderate acne and is often employed as maintenance therapy. Thus, the current study investigated the anti-inflammatory, antibacterial, and restorative effects of sesquiterpene farnesol on acne vulgaris induced by Cutibacterium acnes (C. acnes) in vitro and in a rat model. The minimum inhibitory concentration (MIC) of farnesol against C. acnes was 0.14 mM, and the IC50 of 24 h exposure to farnesol in HaCaT keratinocytes was approximately 1.4 mM. Moreover, 0.8 mM farnesol exhibited the strongest effects in terms of the alleviation of inflammatory responses and abscesses and necrotic tissue repair in C.acnes-induced acne lesions; 0.4 mM farnesol and clindamycin gel also exerted similar actions after a two-time treatment. By contrast, nearly doubling the tissue repair scores, 0.4 mM farnesol displayed great anti-inflammatory and the strongest reparative actions after a four-time treatment, followed by 0.8 mM farnesol and a commercial gel. Approximately 2-10-fold decreases in interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, found by Western blot analysis, were predominantly consistent with the histopathological findings and tissue repair scores. The basal hydroxypropyl methylcellulose (HPMC) gel did not exert anti-inflammatory or reparative effects on rat acne lesions. Our results suggest that the topical application of a gel containing farnesol is a promising alternative remedy for acne vulgaris.