Single intratracheal administration of cross-linked water-soluble acrylic acid polymer causes acute alveolo-interstitial inflammation and the subsequent fibrotic formation possibly via the TGF-ß1 pathway in the lung of rats.

In a Japanese chemical factory, a lung disease like pneumoconiosis appeared at a high rate among workers handling cross-linked water-soluble acrylic acid polymer (CWAAP). To our knowledge, no such case was known in the world until very recently. The present study was designed to elucidate the effect of single intratracheal CWAAP instillation on the lung of rats. The CWAAP group had a significant increase in relative lung weight accompanied by a significant elevation in the number of total cells, total protein concentrations, and myeloperoxidase concentrations in bronchoalveolar lavage fluid when compared to the control group. The histopathological study revealed acute lung inflammation with the destruction of alveoli. The factors promoting fibrosis, macrophages, TGF-ß1, collagen and fibronectin vs. the factors suppressing fibrosis, matrix metalloproteinases were more powerfully driven in the CWAAP group, resultantly leading to fibrotic formation. In turn, we examined if acute lung inflammation and the subsequent fibrotic formation seen in the CWAAP group appeared in the other water-soluble polymer groups. Their histopathological findings were observed only in the polyacrylic acid sodium (PAAS), a monomer of CWAAP, group. The degree of inflammation and fibrogenesis was stronger in the CWAAP group than in the PAAS group. In conclusion, the present study demonstrated the induction of acute lung inflammation and the subsequent fibrotic formation by single intratracheal CWAAP instillation. The structural features of CWAAP that contains many carboxyl groups and cross-linked chains may be responsible for enhanced inflammation and fibrogenesis in the lung.

Transdermal Drug Delivery for Hair Regrowth.

Today, about 50% of men and 15-30% of women suffer from hair loss as well as the associated psychological impact. Drug therapy, especially through topical administration, is the main treatment strategy for stimulating hair regrowth. However, challenges exist due to the skin barrier that hinders drug penetration. To this end, many efforts have been made to enhance drug penetration efficiency. This review focuses on the advancement of the transdermal drug delivery strategies for hair loss therapy reported in the last five years, especially those via nanoformulations for topical administration and microneedles for transdermal delivery. In addition, physical or chemical penetration enhancers are also introduced, which are often applied with the drug delivery systems to achieve a synergy effect.

Lamotrigine Nanoparticle Laden Polymer Composite Oral Dissolving Films for Improving Therapeutic Potential of the Hydrophobic Antiepileptic Molecule.

Lamotrigine is used for neurological disorders and antiepileptic therapy at frequent dosing due to its poor solubility. The present work aims to study the influence of combining the Lamotrigine nanoparticles and polymer composite oral dissolving film to improve the solubility and dissolution kinetics of the drug. The Lamotrigine-Eudragit E100 nanoparticles were synthesized through solvent evaporation followed by precipitation process, which were laden in oral dissolving films through solvent casting technique. The optimized nanoparticles were assessed for particle size, colloidal stability, drug entrapment efficiency, in vitro release profile, physicochemical characteristics, and cytotoxicity. The optimized polymeric nanoparticles of Lamotrigine: Eudragit E100 (1:0.5) exhibited monodispersed particles with 103 nm average size, +7.96 mV zeta potential, and 82.96% ± 1.2% entrapment efficiency. The composite oral matrix films blended with polyvinyl alcohol and polyvinyl pyrrolidone (0.5:0.5 ratio) incorporated with the polymeric nanoparticles demonstrated >64% drug release within 2 h. The nanoparticles and its composite films exhibited 9- and 11-fold higher drug release than pure drug, respectively. The analytical characterization studies proved the formation of nanoparticles with mild drug-polymer interactions and optimum stability, which resulted in enhanced solubility and dissolution of drug. The nanoparticles displayed lesser cytotoxicity to the normal (Vero) cells at concentration of 10-50 µg/mL compared to pure drug. The optimized polymeric nanoparticle loaded oral films could be suitable for in vivo administration of Lamotrigine at low doses to improve bioavailability and therapeutic efficiency with reduced side effects.

Emulgels Containing Carbopol 934P and Different Vegetable Oils for Topical Propolis Delivery: Bioadhesion, Drug Release Profile, and Ex Vivo Skin Permeation Studies.

Topical administration can enable a more efficient therapy based on the improved bioavailability and patient compliance. Wounds and infections can lead to modifications of skin physiology and body protective function. Propolis (PRP) is utilized for skin protection and treatment. However, PRP extracts do not show suitable rheological characteristics and can cause irritation, pain, ulceration, and healing difficulties when they are administered on the harmed skin. Emulgels composed of Carbopol 934P (C934P) and different vegetable oils have been proposed for propolis extract release and may be a good strategy for topical delivery. The aim of this study was to investigate the bioadhesive properties, PRP release profile, skin permeation, and retention, by Franz's diffusion cell and photoacoustic spectroscopy (PS), of these emulgels. Formulations were composed of C934P and passion fruit oil (PF), sweet almond oil (SA), or andiroba oil (AO). PRP or by-product extracts were added to the systems, drug release profile was investigated, and porcine ear skin was utilized for analyses of bioadhesive properties, skin permeation, and retention. All formulations displayed similar bioadhesive force (0.05-0.07 N); PRP release was modified (prolonged), dependent on formulation composition, and mainly governed by diffusion. PS and analysis using diffusion cell showed that the systems could provide dermal permeation and retention, which was more effective for formulations containing AO. Considering the importance of propolis for many skin therapies, the emulgels containing AO for PRP delivery are worthy of biological studies and further clinical evaluation.

Contact dermatitis caused by glucose sensors-15 adult patients tested with a medical device patch test series.

BACKGROUND: Several cases of allergic contact dermatitis (ACD) to the glucose sensor FreeStyle Libre have been reported. Isobornyl acrylate (IBOA) and N,N-dimethylacrylamide (DMAA) are known culprit allergens. OBJECTIVES: To evaluate patients with suspected ACD to FreeStyle Libre in a standardized manner, present causative allergens, and assess patient-reported implications. METHODS: A total of 15 patients with suspected ACD to FreeStyle Libre were patch tested with the Swedish baseline series and a new medical device series. IBOA and DMAA were tested at 0.1% and 0.3% in petrolatum (pet.). Readings were performed on day (D) 3 and D7. Background data, details on skin reactions, and associated implications were assessed using a questionnaire. RESULTS: Thirteen patients were sensitized to IBOA and four to DMAA. Two positive reactions to IBOA and one to DMAA were seen only at 0.3% concentration on D7. Median duration of sensor use before dermatitis onset was 6 months. Half the number of the patients took precautions in everyday life due to sensor-related skin reactions. Six patients discontinued sensor usage. CONCLUSIONS: Patients with suspected ACD to glucose sensors should be evaluated with a relevant patch test series containing IBOA and DMAA. Adding the 0.3% pet. concentration is recommended. The reading on D7 is necessary.

Synthesis and in vitro characterization of a preactivated thiolated acrylic acid/acrylamide-methylpropane sulfonic acid copolymer as a mucoadhesive sprayable polymer.

AIM: Development of a preactivated thiomer as sprayable excipient for mucoadhesive formulations. METHODS: CG4500 (acrylic acid/acrylamide-methyl propane sulfonic acid copolymer) was thiolated by conjugation with L-cysteine and preactivated by further modification with 2-mercaptonicotinic acid (MNA) in a two-step synthesis and characterized regarding degree of modification and cytotoxicity on Caco-2 cells. The mucoadhesive properties of this novel thiomer were evaluated via rheological synergism, tensile and mucosal residence time studies. Furthermore, the sprayability of the thiomer was evaluated. RESULTS: The newly synthesized derivatives CG4500-SH and CG4500-S-S-MNA showed mean coupling rates of 651 µmol thiol groups and 264 µmol MNA per gram polymer, respectively. Even for the unmodified polymer a rheological synergism was observed with isolated porcine intestinal mucus, which was 2.81-fold higher in case of the preactivated thiomer. Mucoadhesion studies on freshly excised porcine intestinal mucosa confirmed these results via a 2.43-fold higher total work of adhesion and a 2.31-fold higher mucosal residence time of the preactivated thiomer. In sprayability tests it was shown that solutions of the preactivated thiomer could be sprayed in concentrations up to 12% (m/V). CONCLUSION: The novel polymer CG4500-S-S-MNA is a promising sprayable excipient for mucoadhesive formulations.

Enhanced regeneration of osteochondral defects by using an aggrecanase-1 responsively degradable and N-cadherin mimetic peptide-conjugated hydrogel loaded with BMSCs.

Due to the poor self-repair capabilities of articular cartilage, chondral or osteochondral injuries are difficult to be recovered. In this study, an N-cadherin mimetic peptide sequence HAVDIGGGC (HAV) was conjugated to direct cell-cell interactions, and an aggrecanase-1 cleavable peptide sequence CRDTEGE-ARGSVIDRC (ACpep) was used to crosslink hyperbranched PEG-based multi-acrylate polymer (HBPEG) with cysteamine-modified chondroitin sulfate (Cys-CS), obtaining an aggrecanase-1 responsively degradable and HAV-conjugated hydrogel ((HAV-HBPEG)-CS-ACpep). A HBPEG-CS-ACpep hydrogel without the HAV motif was also prepared. The two hydrogels exhibited similar equilibrium swelling ratios, elastic moduli and pore sizes after lyophilization, indicating the negligible influence of conjugated HAV on the crosslinking networks and mechanical properties of the hydrogels. After being degraded in PBS, aggrecanase-1 (ADAMTS4) and trypsin, the HBPEG-CS-ACpep hydrogel exhibited significantly decreased elastic moduli with a much lower value when incubated in enzyme solutions. The two hydrogels could maintain the viability of encapsulated bone marrow-derived mesenchymal stem cells (BMSCs), and the (HAV-HBPEG)-CS-ACpep hydrogel better promoted the cell-cell interactions. After being implanted into osteochondral defects in rabbits for 18 weeks, the two cell-laden hydrogel groups achieved better repair effects than the blank control group. Moreover, hyaline cartilage was formed in the (HAV-HBPEG)-CS-ACpep/BMSCs hydrogel group, while a hybrid of hyaline cartilage and fibrocartilage was found in the HBPEG-CS-ACpep/BMSCs hydrogel group.

Synthesis, Characterization and Safety Profiling of Eudragit-Based pHResponsive Hydrogels: A Promising Platform for Colonic Delivery of Losartan Potassium.

OBJECTIVE: The aim of the present study was to design an efficient delivery system with an anticipated swelling and drug release properties for a prolonged drug release as well as to target colon for various hydrophilic drugs. METHOD: For this purpose, the pH-responsive hydrogel comprising a combination of Eudragit and acrylic acid was formed. The hydrogels were characterized for spectral (FTIR), thermal (TGA/DSC), structural (XRD), and morphological (SEM) investigations. Oral tolerability was assessed in rabbits for biocompatibility and oral use of the prepared hydrogels. RESULTS: The results showed that an increased incorporation of Eudragit and cross-linking agent retorted the swelling, drug loading, and drug release properties at both acid (pH 1.2) and basic pH (pH 6.8 and 7.4) , while acrylic acid presented the inverse results. The oral tolerability and toxicity studies depicted that the developed hydrogels were safe up to 3800 mg/kg body weight and caused no hematological or histopathological changes when compared with the control group. CONCLUSION: Therefore, the newly developed formulations presented adequate swelling, drug loading, release behavior, and biocompatibility properties and thus can be used as a promising tool for the colonic delivery of various hydrophilic drugs.

Ethyl acrylate: influence of sex or atopy on perceptual ratings and eye blink frequency.

Occupational exposure limits (OELs) are derived for protection from health hazards, assuming that exposed subjects are healthy adult workers. Whether differences in susceptibility to sensory irritation effects from airborne chemicals have to be taken into account is currently under discussion. Thus, we chose atopics as a healthy but possibly susceptible subpopulation that can be identified with a clinical test. To investigate the influence of sex or atopy on sensitivity to airborne chemicals, 22 subjects were exposed for 4 h to ethyl acrylate at three concentrations: 0.05 ppm (odor threshold; sham), 5 ppm (constant), and varying exposure between 0 and 10 ppm. Odor intensity decreased and eye irritation ratings increased in a dose-dependent manner, reflecting the time course of the exposure scenarios. The reports of moderate-to-strong eye irritation were verified by significant increases in eye blink frequency. Our results show that women reported subjective eye irritation to an increasing degree. However, these sex-related differences in ratings could not be verified by objective assessment of eye blink frequency. Atopic subjects reported higher odor intensity than non-atopic subjects, but only during the sham (odorous but not irritating) exposure condition. Differences in ratings on annoyance, and eye or nose irritation were not found. Furthermore, the study revealed that atopic subjects might belong to a group of subjects with frequent eye blink activity. Although the relative increase in blink rates was more pronounced in non-atopic subjects, atopic subjects had significant higher blink rates at the end of the exposure to varying ethyl acrylate concentrations. Our results do not support that atopy enhances chemosensory effects if only the increase of blink rates and not the absolute height are considered as adverse effect. Nevertheless, the results indicate that individuals with frequent eye blink activity should be distinguished from those with normal eye blink activity while investigating blink rates as objective parameter of eye irritation.

Efectividad de la película transparente de polímero de acrilato en la prevención y tratamiento de lesiones de la piel. Revisión bibliográfica / Effectiveness of transparent acrylate polymer film in the prevention and treatment of skin lesions. Bibliographic review

Objetivos: Obtener evidencias disponibles sobre la eficacia de la película transparente de polímero de acrilato o producto barrera no irritante (PBNI) en la prevención y tratamiento de lesiones de la piel. Método: Revisión de la literatura a partir de la búsqueda de ensayos clínicos aleatorizados y estudios observacionales sobre los PBNI en PubMed, CINAHL y CUIDEN, publicados entre 2009 y 2018, ya que existe una revisión sistemática anterior. Resultados: Dos estudios evidenciaron reducción de complicaciones cutáneas aplicando PBNI antes de la colocación de apósitos de sujeción para catéteres venosos centrales. Respecto a las complicaciones cutáneas de la radioterapia, un estudio observó que los PBNI solo ayudaban a retrasar la intensidad del prurito. Un trabajo sobre la prevención y tratamiento de la dermatitis por incontinencia constataba que los PBNI son una buena alternativa a las cremas barrera, ya que tienen mejor aceptabilidad y cuestan menos de aplicar y retirar. En el ámbito del exceso de exudado y sus complicaciones en la zona periulceral, dos estudios coincidieron en la efectividad de los PBNI para reducir el diámetro de la superficie, exudado y esfacelo. Conclusiones: Los PBNI ayudan a prevenir las lesiones de la piel provocadas por apósitos de catéter; en la radiodermitis solo ayudan a disminuir el prurito; en las dermatitis por incontinencia son alternativa a la cremas barrera; en el control de las complicaciones del exudado en la zona periulceral en lesiones de extremidad inferior son igual de efectivos que las cremas con zinc

Objectives: To obtain available evidence on the efficacy of transparent film of acrylate polymer or non-irritating barrier product (PBNI) in the prevention and treatment of skin lesions. Method: Review of the literature based on the search of randomized clinical trials and observational studies on PBNI in PubMed, CINAHL and CUIDEN published between 2009 and 2018, since there is a previous systematic review. Results: Two studies showed reduction of cutaneous complications by applying PBNI before the placement of fixation dressings for central venous catheters. Regarding the cutaneous complications of radiotherapy, one study observed that PBNI only helped to delay the intensity of pruritus. A work on the prevention and treatment of incontinence dermatitis found that PBNI are a good alternative to barrier creams, since they have better acceptability and cost less to apply and remove. In the area of excess exudate and its complications in the periulceral zone, two studies agreed on the effectiveness of PBNI to reduce the diameter of the surface, exudate and slough. Conclusions: PBNI helps to prevent skin lesions caused by catheter dressings, in radiodermatitis they only help to reduce pruritus, in incontinence dermatitis they are an alternative to barrier creams, in the control of the complications of exudate in the periulceral zone in lower limb injuries are just as effective as creams with zinc

Effectiveness of Nursing Interventions to Prevent Dry Eye in Critically Ill Patients.

BACKGROUND: Critically ill patients are susceptible to the development of dry eye. Few studies have been conducted on how to best prevent and treat this condition. OBJECTIVE: To compare the effectiveness of 2 nursing interventions in preventing dry eye in adult intensive care unit patients: liquid artificial tears (Lacribell; Latinofarma) and artificial tears gel (Vidisic Gel; Bausch and Lomb). METHODS: In this randomized controlled trial, 140 participants were randomly assigned to 1 of 2 treatment groups: a liquid artificial tears group (n = 70) and an artificial tears gel group (n = 70). The study inclusion criteria were as follows: admission to the intensive care unit, age of 18 years or older, no diagnosis of dry eye at admission, receipt of mechanical ventilation, blink rate of less than 5 times per minute, and a score of 7 or less on the Glasgow Coma Scale. On 5 consecutive days, a single researcher who was unaware of the treatment assignment assessed the participants' eyes using the fluorescein eye stain test and the Schirmer test for dry eye. RESULTS: Dry eye developed in 21% of participants who received liquid artificial tears versus 9% of participants who received artificial tears gel (P = .04). CONCLUSIONS: In this study, artificial tears gel was superior to liquid artificial tears in preventing the development of dry eye. These results may help nurses deliver evidence-based eye care aimed at reducing the risk of dry eye in critically ill patients.

Risk assessment and QbD based optimization of an Eprosartan mesylate nanosuspension: In-vitro characterization, PAMPA and in-vivo assessment.

Quality by design (QbD) principles were implemented to understand the product and process variables of sonoprecipitation technique, for preparation of eprosartan mesylate (EM) nanosuspension. Quality risk management approach was utilized to identify and assess high-risk attributes affecting critical quality attributes (CQA's), prioritizing the number of experiments. The effect of critical material attributes (CMA's) and critical process parameters (CPP's) (soluplus concentration, drug concentration ultrasonication amplitude) on z-average particle size and PDI were investigated using a central composite face-centered design (CCF). Further, design space with criteria set of CMA's and CPP's was established to offer assurance of quality. The optimal formulation, identified using numerical optimization method, was further lyophilized and evaluated for redispersibility, solubility saturation, dissolution kinetic and in-vitro dissolution behavior. The EM nanoparticles were in an amorphous state as confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. The stability study conducted for a span of 6 months attests physical and chemical stability of EM dry nanosuspension in an amorphous state when stored at 4 °C. The enhanced solubility and in-vitro dissolution of EM nanosuspension may be attributed to the reduced particle size and alteration of the physical state from a crystalline to an amorphous state. Further, the optimized formulation was subjected to in-vitro and ex-vivo transport study using parallel artificial membrane permeability assay (PAMPA) and rat everted gut sac model respectively. The transport studies revealed successful permeation enhancement of EM nanoparticle when compared with EM API and physical mixture (PM). The absolute bioavailability of EM API was 7.1% and improved to 39.9% for EM nanosuspension, suggesting that nanoformulation had overcome solubility and permeability limited bioavailability which was observed with EM API.

Quality by design driven development of resveratrol loaded ethosomal hydrogel for improved dermatological benefits via enhanced skin permeation and retention.

Resveratrol is a potent anti-oxidant agent and can be used for the effective management of different skin conditions like extrinsic skin ageing, psoriasis, etc. The objective of this research was to develop a dermal delivery system of resveratrol for its improved dermatological benefits for achieving its enhanced skin deposition profile with limited systemic exposure. Resveratrol loaded ethosomal hydrogel was developed and optimized using systematic Quality by Design approach. Firstly, the quality target product profile (QTPP) of ethosomal formulation was defined and critical quality attributes (CQAs) and critical material attributes (CMAs) were screened through risk assessment studies based on fish bone diagram. 32 full factorial design using Design Expert software was employed to optimize the selected CMAs. Concentration of phospholipid (X1) and concentration of ethanol (X2) were selected as independent CMAs. Vesicle size (Y1), entrapment efficiency (Y2), permeation flux (Y3) and drug deposition in dermal layer (Y4) were evaluated as dependant CQAs. Optimized formulation was then evaluated for physicochemical and skin permeation properties. Ethosomal hydrogel was able to significantly enhance the skin permeation parameters and skin deposition of resveratrol in comparison to the conventional cream. The results were highly ratified by CLSM studies in which ethosomal hydrogel was found to be vastly scattered in the deeper skin layers. Thus, there is evidence that systemically developed ethosomal gel can deliver enhanced amounts of bioactives into the skin and it is expected that a number of products for dermal/transdermal applications will be developed in the future based on it.

Preclinical and clinical evaluation of a novel synthetic bioresorbable, on-demand, light-activated sealant in vascular reconstruction.

BACKGROUND: Synthetic vascular material use, particularly polytetrafluoroethylene- (PTFE) -based, can be associated with bleeding, which may increase operative time and blood loss. None of the commercially available sealants designed to ensure hemostasis combine bioresorption, high viscosity, hydrophobicity, and compliance with the underlying tissue and on-demand activation. METHODS: A study was designed to assess the biocompatibility and in-vivo performance and bioresorption of a new synthetic on-demand light-activated poly(glycerol-sebacate) acrylate- (PGSA) -based SETALIUM™ Vascular Sealant (TISSIUM, Paris, France) in three large animal studies of open vascular carotid and aortic surgery. The pre-clinical results were then translated into a clinical setting in a prospective, single-arm multicenter study in patients requiring carotid endarterectomy using an ePTFE patch. RESULTS: The biocompatibility testing showed that the PGSA-based SETALIUM™ Vascular Sealant did not induce any significant toxic reaction at a standard clinical dose nor at doses up to 40 times the equivalent intended clinical dose. The PGSA-based sealant was shown to be non-pyrogenic, non-sensitizing, non-irritant, non-clastogenic, and non-mutagenic. The animal studies showed excellent performance and safety results, with clinically significant hemostasis achieved in 100% of the animals in both carotid and aorta studies and excellent local tolerance. Histopathology and morphometric analyses showed surface-based gradual and sustained bioresorption of the PGSA-based sealant up to 86% at 12 months. In the clinical study, the application of the PGSA-based sealant resulted in good performance and safety, with immediate hemostasis achieved in 84% of the cases and no adverse event related to the sealant reported through the one-year follow-up. CONCLUSIONS: The new synthetic on-demand light activated PGSA-based SETALIUM™ Vascular Sealant investigated in our studies demonstrated good biocompatibility, sustained and gradual surface based bioresorption, and acceptable safety profile in animal studies. In addition, the first in-human use showed that the sealant is a safe and effective alternative to achieve fast and controlled hemostasis in vascular carotid reconstructions. A larger randomized controlled study will allow further validation of these encouraging preliminary results.

Urinary metabolites of the UV filter octocrylene in humans as biomarkers of exposure.

Octocrylene (OC) is a UV filter used in sun screens and other personal care products, but also in polymers and food contact materials for stabilization. In this study, we investigate human OC metabolism and urinary excretion after oral dosage of approx. 5 mg OC [≙ 61.8-89.5 µg/(kg body weight)] in three male volunteers. In a screening approach, we tentatively identified six urinary OC metabolites. For three, renal elimination kinetics was quantitatively investigated using authentic standards: the sidechain oxidation product 2-ethyl-5-hydroxyhexyl 2-cyano-3,3-diphenyl acrylate (5OH-OC), the beta-oxidation product 2-(carboxymethyl)butyl 2-cyano-3,3-diphenyl acrylate (dinor OC carboxylic acid; DOCCA), and the ester hydrolysis product 2-cyano-3,3-diphenylacrylic acid (CPAA). CPAA was the major urinary metabolite, representing 45% (range 40-50%) of the OC dose. 5OH-OC and DOCCA were only minor metabolites with low, but highly consistent renal conversion factors of 0.008% (0.005-0.011%) and 0.13% (0.11-0.16%), respectively. Peak urinary metabolite concentrations were observed between 3.2 h and 4.2 h postdose. All three metabolites were excreted with biphasic elimination kinetics, with considerably longer elimination half-lives for DOCCA (1st phase: 3.0 h; 2nd phase: 16 h) and CPAA (5.7 h and 16 h) compared to 5OH-OC (1.3 h and 6.4 h). 99% of all 5OH-OC was excreted within 24 h compared to 82% of DOCCA and 77% of CPAA. After dermal exposure, we detected the same metabolites with similar ratios in urine, however, at much lower concentrations and with considerably delayed elimination.

Inhibition of post-transcriptional gene silencing of chalcone synthase genes in petunia picotee petals by fluacrypyrim.

In petals of picotee petunia (Petunia hybrida) cultivars, margin-specific post-transcriptional gene silencing (PTGS) of chalcone synthase A (CHSA) inhibits anthocyanin biosynthesis, resulting in marginal white tissue formation. In this study, we found that a low molecular mass compound, fluacrypyrim, inhibits PTGS of CHSA, and we explored the site-specific PTGS mechanism of operation. Fluacrypyrim treatment abolished the picotee pattern and eliminated site-specific differences in the levels of anthocyanin-related compounds, CHSA expression, and CHSA small interfering RNA (siRNA). In addition, fluacrypyrim abolished the petunia star-type pattern, which is also caused by PTGS of CHSA. Fluacrypyrim treatment was effective only at the early floral developmental stage and predominantly eliminated siRNA derived from CHS genes; i.e. siRNA derived from other genes remained at a comparable level. Fluacrypyrim probably targets the induction of PTGS that specifically operates for CHS genes in petunia picotee flowers, rather than common PTGS maintenance mechanisms that degrade mRNAs and generate siRNA. Upon treatment, the proportion of colored tissue increased due to a shift of the border between white and colored sites toward the margin in a time- and dose-dependent manner. These findings imply that the fluacrypyrim-targeted PTGS induction is completed gradually and its strength is attenuated from the margins to the center of petunia picotee petals.

Folate receptor targeted delivery of paclitaxel to breast cancer cells via folic acid conjugated graphene oxide grafted methyl acrylate nanocarrier.

The adaptability, joint with a large surface area, electronic flexibility, high intrinsic mobility, high mechanical strength and supreme thermal conductivity have condensed graphene family materials attractive as technological tools of the drug delivery system. In this present study, investigate a modified graphene oxide-methyl acrylate (GO-g-MA) nanocarrier for targeted anti-cancer drug delivery in breast cancer cells and the GO-g-MA fascinated with folic acidas a targeting ligand to target the cancer cells. Paclitaxel (PTX) was assembled through π-π stacking, hydrophophic interaction on the surface of the GO-g-MA/FA carrier. Structural modification of GO-g-MA, functionalization of targeting ligands GO-g-MA/FA and drug loaded GO-g-MA/FA-PTX was characterized and confirmed through FTIR, XRD, SEM,TEM and AFM analysis. The in-vitro drug release pattern of PTX from the GO-g-MA/FA was examined in different pH ranges. An MTT assay was performed to evaluate the cytotoxicity behaviour of the carrier and PTX loaded nanocarrier in the human breast cancer cell line (MDA-MB-231). GO-g-MA/FA-PTX carrier showed that 39% of cytotoxic effect. Furthermore, the in-vivo (DMBA induced breast cancer rats) studies were carried out and treatment with PTX- loaded GO-g-MA/FA nanocarrier attenuates the levels of mitochondrial citric acids enzymes to near normal.

An adjuvant compound that enhances immunogenicity at fractional doses of the Sabin-inactivated poliovirus vaccine (sIPV) with a long duration of protection in a rat model.

BACKGROUND: At the same dosage, the new generation of Sabin-inactivated poliovirus vaccine (sIPV) is less immunogenic than the traditional oral polio vaccine (OPV) dosage in China. The useful adjuvant might be a necessary strategy to strengthen the immune protective effects. METHODS: In this study, we produced an adjuvant compound (named KML05) that could promote immunogenicity and fractional doses of sIPV with a long duration of protection in a rat model. The compound adjuvant had both advantages and a function of MF59 and carbopol971P. RESULTS: The effect seroconversion of experimental animals immunized with KML05 could be extended to one-eighth of the dose. According to the result of the geometric mean titers (GMTs), KML05 adjuvant could save eight times the amount of sIPV D-antigen usage, but aluminum hydroxide adjuvant could save twice at the same titers. Additionally, it was found that there was a significant difference in the GMT titer of poliovirus type 2 between animals immunized by KML05 and alum adjuvant (P < 0.05). At 12th-month postvaccination, the neutralization titers stimulated by IPV-KML05 were maintained over a longer time period in immunized animals. CONCLUSION: Our research team developed KML05 adjuvant, which combined carbopol971P with MF59, increased antibody responses to sIPV for a longer duration of protection in a rat model.

In vivo evaluation of bacterial cellulose/acrylic acid wound dressing hydrogel containing keratinocytes and fibroblasts for burn wounds.

The healing of wounds, including those from burns, currently exerts a burden on healthcare systems worldwide. Hydrogels are widely used as wound dressings and in the field of tissue engineering. The popularity of bacterial cellulose-based hydrogels has increased owing to their biocompatibility. Previous study demonstrated that bacterial cellulose/acrylic acid (BC/AA) hydrogel increased the healing rate of burn wound. This in vivo study using athymic mice has extended the use of BC/AA hydrogel by the addition of human epidermal keratinocytes and human dermal fibroblasts. The results showed that hydrogel loaded with cells produces the greatest acceleration on burn wound healing, followed by treatment with hydrogel alone, compared with the untreated group. The percentage wound reduction on day 13 in the mice treated with hydrogel loaded with cells (77.34 ± 6.21%) was significantly higher than that in the control-treated mice (64.79 ± 6.84%). Histological analysis, the expression of collagen type I via immunohistochemistry, and transmission electron microscopy indicated a greater deposition of collagen in the mice treated with hydrogel loaded with cells than in the mice administered other treatments. Therefore, the BC/AA hydrogel has promising application as a wound dressing and a cell carrier.

In-vitro study of the influence of octocrylene on a selected metastatic melanoma cell line.

BACKGROUND: Octocrylene (OCT) is one of the most widespread chemical UV filters used in sunscreens and cosmetic products. Despite the use of sunscreens and personal care products over decades, melanoma as the most serious and aggressive form of skin cancer is still a cause of concern. Hence the aim of this study was to investigate any potential influence of OCT on metabolic activity, cytotoxicity and ABCB5 mRNA expression in melanoma cells. The ABCB5 transmembrane protein was tested due to its well-known role in the initiation, invasion and metastatic spread of various cancers, including melanoma. METHODS: Metastatic melanoma cell line WM-266-4 (ATCC) was incubated with selected concentrations of OCT and for different time intervals. The MTT and LDH assays to measure the cells' metabolic activity and cytotoxicity were used respectively. Target gene (ABCB5) expression was detected by quantitative real-time PCR (qRT-PCR), using TaqMan® chemistry. RESULTS: Our results suggest decreased metastatic melanoma cells' metabolic activity, increased cytotoxicity and increased ABCB5 mRNA expression (P<0.05) with longer time of exposure to OCT as compared to control cells. Accordingly, we suspect that the surviving cells are more invasive and aggressive, which might explain their microscopically observed cannibalistic activity. CONCLUSIONS: With this study, we elucidate a new promising field for further research to contribute to etiology and prevention of melanoma.