Sequential administration of PEG-Span 80 niosome enhances anti-tumor effect of doxorubicin-containing PEG liposome.

To improve the anti-tumor effect of polyethylene glycol-modified liposome containing doxorubicin (DOX-PEG liposome), the effect of sequential administration of PEG-Span 80 niosome was investigated for Colon-26 cancer cells (C26)-bearing mice. The concept of the current study is as follows: Since both particulates would be accumulated in the tumor tissue due to the enhanced permeability and retention (EPR) effect, PEG-Span 80 niosome, mainly composed of synthetic surfactant (Span 80), would interact with DOX-PEG liposome and be a trigger to induce the release of DOX from the liposome within the tumor tissue, leading to the improvement of anti-tumor effect of DOX-PEG liposome. To find out an adequate liposome for this strategy, several PEG liposomes with different compositions were examined in terms of drug release enhancement and it was found that PEG-Span80 niosome could significantly enhance the release of calcein and DOX from a PEG liposome composed of 90% hydrogenated soybean phosphatidylcholine (HSPC) and 10% cholesterol. The sequential administration of PEG-Span 80 niosome at 24 or 48 h after dosing of DOX-PEG liposome provided a higher anti-tumor effect than the single dose of DOX-PEG liposome in the C26-bearing mice. Particularly, the 24 h-later dosing of PEG-Span 80 niosome has been found to be more effective than the 48 h-later dosing. It was also confirmed that the coexistence of PEG-Span 80 niosome with DOX-PEG liposome in 50% serum or in 50% supernatant of tumor tissue homogenate significantly increased DOX release from PEG liposome, suggesting that DOX release from DOX-PEG liposome within tumor tissue would be enhanced via the interaction with PEG-Span 80 niosome. This strategy would lead to the safer and more inexpensive chemotherapy, since it could make it possible to provide the better anti-tumor effect by utilizing the lower dose of DOX.

Myroxylon pereirae (balsam of Peru): Still worth testing?

BACKGROUND: Because Myroxylon pereirae (MP), or balsam of Peru, is nowadays almost not used "as such," and fragrance mix 1 (FM1) apparently is more sensitive in detecting fragrance allergy, the usefulness of testing MP in baseline series was recently questioned. OBJECTIVES: Identification of the number of clinically relevant patch test reactions to MP not detected by FM1. METHODS: Retrospective analysis of 12 030 patients patch tested with MP and FM1 for contact dermatitis between January 2018 and December 2019 in 13 Italian dermatology clinics. RESULTS: Four hundred thirty-nine patients (3.6%) had a positive patch test reaction to MP; 437 (3.6%) had a positive patch test reaction to FM1. Positive reactions to both MP and FM1 were observed in 119 subjects (1.0%), 310 (2.6%) reacted to MP only, 304 (2.5%) to FM1 only, 5 to MP and sorbitan sesquioleate (SSO), 9 to FM1 and SSO, and 5 to MP, FM1, and SSO. Single sensitizations were clinically relevant in 75.2% of cases for MP (62.9% current, 12.3% past) and 76.3% for FM1 (70.1% current, 6.2% past). CONCLUSIONS: Based on our results, MP appears to be still worth testing along with FM1 in baseline series, because it allows detection of a remarkable number of fragrance allergies, often relevant, which would be otherwise missed.

A polyoxyethylene sorbitan oleate modified hollow gold nanoparticle system to escape macrophage phagocytosis designed for triple combination lung cancer therapy via LDL-R mediated endocytosis.

Presently, a combination of chemotherapy, radiotherapy, thermotherapy, and other treatments has become a hot topic of research for the treatment of cancer, especially lung cancer. In this study, novel hollow gold nanoparticles (HGNPs) were used as drug carriers, and in order to improve the targeting ability of HGNPs to a lung tumor site, polyoxyethylene sorbitol oleate (PSO) was chosen here as a target ligand since it can be specifically recognized by the low-density lipoprotein (LDL) receptor which is usually over expressed on A549 lung cancer cells. In this way, a PSO-modified doxorubicin-loaded HGNP drug delivery system (PSO-HGNPs-DOX) was constructed and its physicochemical properties, photothermal conversion ability, and drug release of PSO-HGNPs-DOX was investigated. Further, the effects of triple combination therapy, the intracellular uptake, and the ability to escape macrophage phagocytosis of PSO-HGNPs-DOX were also studied using A549 cells in vitro. In addition, an in vivo mouse model was also used to study the targeting of PSO-HGNPs-DOX to lung cancer. PSO-HGNPs-DOX demonstrated a good triple therapeutic effect for lung cancer (A549 cell viability was only 10% at 500 µM) by LDL receptor mediated endocytosis and was able to escape macrophage phagocytosis to enhance its accumulation at the target site. Therefore, PSO-HGNPs-DOX is a novel, safe, promising, and targeted drug carrier designed for triple combination lung cancer therapy which should be further studied for such applications.

D-Tagatose Effectively Reduces the Number of Streptococcus mutans and Oral Bacteria in Healthy Adult Subjects: A Chewing Gum Pilot Study and Randomized Clinical Trial.

We examined the effect of D-Tagatose on the growth of oral bacteria including Streptococcus mutans (S. mutans). Saliva collected from 10 healthy volunteers was plated on BHI medium (to culture total oral bacteria) and MBS medium (to culture S. mutans, specifically). Agar plates of BHI or MBS containing xylitol or D-Tagatose were cultured under aerobic or anaerobic conditions. We then counted the number of colonies. In BHI plates containing D-Tagatose, a complete and significant reduction of bacteria occurred under both aerobic and anaerobic conditions. In MSB medium, significant reduction of S. mutans was also observed. We then performed a doubleblind parallel randomized trial with 19 healthy volunteers. They chewed gum containing xylitol, D-Tagatose, or both for 4 weeks, and their saliva was collected weekly and plated on BHI and MSB media. These plates were cultured under anaerobic conditions. Total bacteria and S. mutans were not effectively reduced in either the D-Tagatose or xylitol gum group. However, S. mutans was significantly reduced in volunteers chewing gum containing both D-Tagatose and xylitol. Thus, D-Tagatose inhibited the growth of S. mutans and many types of oral bacteria, indicating that D-Tagatose intake may help prevent dental caries, periodontitis, and many oral diseases.

Effect of fructose and its epimers on postprandial carbohydrate metabolism: A systematic review and meta-analysis.

AIMS: To synthesize the evidence of the effect of small doses (≤30-g/meal) of fructose and its epimers (allulose, tagatose, and sorbose) on the postprandial glucose and insulin response to carbohydrate-containing meals. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through to April 9, 2019. We included randomized (RCTs) and non-randomized acute, single-meal, controlled feeding trials that added ≤30-g of fructose or its epimers either prior to or with a carbohydrate-containing meal compared with the same meal alone. Outcomes included the incremental area under the curve (iAUC) for glucose and insulin, the Matsuda Insulin Sensitivity Index, and the Early Insulin Secretion Index. Data were expressed as ratio of means (RoM) with 95% CIs and pooled using the inverse variance method. The overall certainty of the evidence was evaluated using GRADE. RESULTS: Forty trial comparisons (n = 400) were included (none for sorbose). Allulose significantly reduced the postprandial iAUC glucose response by 10% (0.90 [0.84 to 0.96], P < 0.01). Tagatose significantly reduced the postprandial iAUC insulin response by 25% (0.75 [0.62 to 0.91], P < 0.01) and showed a non-significant 3% reduction in the postprandial iAUC glucose response (0.97 [0.94 to 1.00], P = 0.07). There was no effect of fructose on any outcome. The certainty of the evidence was graded as low to moderate for fructose, moderate for allulose, and low for tagatose. CONCLUSIONS: Small doses of allulose and tagatose, but not fructose, lead to modest improvements on postprandial glucose and insulin regulation. There is a need for long-term RCTs to confirm the sustainability of these improvements.

Novel antipsoriatic fluidized spanlastic nanovesicles: In vitro physicochemical characterization, ex vivo cutaneous retention and exploratory clinical therapeutic efficacy.

Tazarotene (TAZ) is a topical synthetic retinoid used in psoriasis treatment, however, it is extremely lipophilic and exhibits skin irritation. Research is in a state of continuous advancement in the field of nanocarriers fabrication, and in this regard, we investigated the formulation of novel topically oriented nanovesicles; representing a combination of spanlastics and penetration enhancer vesicles, to be termed (fluidized-SNs). TAZ-loaded fluidized SNs were physicochemically characterized, tested for ex vivo cutaneous retention, and the selected formulation was compared with the marketed product Acnitaz® regarding clinical antipsoriatic activity. The selected fluidized-SNs enriched with 1% cineole exhibited high entrapment for TAZ (76.19%), suitable size and zeta potential of 241.5 ±â€¯5.68 nm and -36.10 ±â€¯2.50 mV respectively, and retaining of stability after refrigeration storage for one month. As hypothesized, cineole enriched fluidized-SNs exhibited remarkable TAZ deposition amounting to a total of 81.51% in the different skin layers. Upon clinical assessment, the presented formulation displayed superior traits compared to the marketed product, in terms of dermoscopic imaging, morphometric analysis of psoriatic lesions, and statistical analysis of PASI scores. Results confirmed that the prepared novel fluidized spanlastics formulation holds great promise for the treatment of psoriasis, and its benefit should futuristically be investigated in other topical diseases.

Novel bergamot oil nanospanlastics combined with PUVB therapy as a clinically translatable approach for vitiligo treatment.

The impact of nanomedicine has grown in the current decade; however, only very few clinical translational attempts have been realized. Therefore in the present study, we hypothesized that bergamot oil, a psoralen-containing oil, would produce an optimized melanogenic effect in the clinical treatment of vitiligo when loaded within an elastic nanocarrier (spanlastics) and combined with PUVB for activation of psoralens. Spanlastics were prepared and characterized for particle size, physical stability, in vitro release, thermal behavior, deformability, morphology, and in vitro photostability. The efficacy of the selected formula was tested histopathologically on rat skin and clinically translated in patients suffering from vitiligo. Results revealed that the spanlastics were of reasonable nanosize, deformable, and provided sustained release of bergamot oil. The incorporation of bergamot oil within spanlastics improved its photostability and its photodynamic activity. Spanlastics exhibited promising clinical results in terms of extent and onset of repigmentation in vitiligo patients. Therefore, it can be concluded that spanlastics can be introduced as a promising nanotreatment modality for vitiligo.

Cationized hyaluronic acid coated spanlastics for cyclosporine A ocular delivery: Prolonged ocular retention, enhanced corneal permeation and improved tear production.

The aim of this work was to design and evaluate novel cationized hyaluronic acid coated spanlastics (CHASVs), with the immunosuppressive peptide cyclosporine A (CsA) as the model drug. CHASVs exhibited ideal size, zeta potential, pH, osmolarity and entrapment efficiency. The developed CHASVs provided a surface tension of 34.98 ±â€¯0.19 mN/m, a contact angle of 21.07 ±â€¯3.56° and a viscosity of 9-12 mPa·s, which reflected favorable wetting and bioadhesion properties. From the in vitro release study, the sustain release property could also be seen. These proved the availability of CsA by ocular delivery was improved. With an apparent permeation coefficient of 5.22 × 10-6 cm/s and CsA residual of 312.18 ±â€¯1.34 µg/g, CHASVs proved to enhance corneal permeation and accumulation of CsA compared with commercial emulsions. In vivo Draize test showed no signs of acute and chronic ocular toxicity of CHASVs formulations to the eyes of rabbits. Finally, schirmer tear test, tear ferning test and histologic analysis reflected that CHASVs showed significant therapeutic effect and improved tear production in dry eye. Results revealed that CHASVs could be a promising delivery system for CsA and employed as an ideal alternative to commercial emulsions for the treatment of dry eye syndrome.

Effect of the Lactobacillus rhamnosus strain GG and tagatose as a synbiotic combination in a dextran sulfate sodium-induced colitis murine model.

Synbiotics, a combination of prebiotics and probiotics, produce synergistic effects to promote gastrointestinal health. Herein, we investigated the synbiotic interaction between the Lactobacillus rhamnosus strain GG (LGG; a probiotic strain) and tagatose (a prebiotic) in a dextran sulfate sodium (DSS)-induced colitis murine model. Initially, body weight, food intake, and clinical features were dramatically decreased after treatment with DSS, and the addition of LGG, tagatose, or both ameliorated these effects. In our pyrosequencing analysis of fecal microbiota, DSS treatment increased the abundance of Proteobacteria and decreased that of Firmicutes. When LGG and tagatose were administered as synbiotics, the gut microbiota composition recovered from the dysbiosis caused by DSS treatment. In particular, the abundance of Bacteroides, Lactobacillus, and Akkermansia was significantly associated with probiotic, prebiotic, and synbiotic treatments. Taken together, our results suggest that LGG and tagatose as synbiotics can alleviate colitis, and synbiotics could be applied as dietary supplements in dairy foods such as yogurt and cheese.

Excipient selection and aerodynamic characterization of nebulized lipid-based nanoemulsion loaded with docetaxel for lung cancer treatment.

Docetaxel has demonstrated extraordinary anticancer effects on lung cancer. However, lack of optimal bioavailability due to poor solubility and high toxicity at its therapeutic dose has hampered the clinical use of this anticancer drug. Development of nanoemulsion formulation along with biocompatible excipients aimed for pulmonary delivery is a potential strategy to deliver this poorly aqueous soluble drug with improved bioavailability and biocompatibility. In this work, screening and selection of pharmaceutically acceptable excipients at their minimal optimal concentration have been conducted. The selected nanoemulsion formulations were prepared using high-energy emulsification technique and subjected to physicochemical and aerodynamic characterizations. The formulated nanoemulsion had mean particle size and ζ-potential in the range of 90 to 110 nm and - 30 to - 40 mV respectively, indicating high colloidal stability. The pH, osmolality, and viscosity of the systems met the ideal requirement for pulmonary application. The DNE4 formulation exhibited slow drug release and excellent stability even under the influence of extreme environmental conditions. This was further confirmed by transmission electron microscopy as uniform spherical droplets in nanometer range were observed after storage at 45 ± 1 °C for 3 months indicating high thermal stability. The nebulized DNE4 exhibited desirable aerosolization properties for pulmonary delivery application and found to be more selective on human lung carcinoma cell (A549) than normal cell (MRC-5). Hence, these characteristics make the formulation a great candidate for the potential use as a carrier system for docetaxel in targeting lung cancer via pulmonary delivery.

Freeze-dried bioadhesive vaginal bigels for controlled release of Tenofovir.

Nowadays, million women live with the human immunodeficiency virus (HIV) worldwide and many of them are dying per year, particularly in Sub-Saharan Africa. The development of systems that can be accessed by this population group to prevent the sexual transmission of the virus is therefore necessary. The aim of this work was the formulation of freeze-dried bioadhesive vaginal bigels releasing Tenofovir in a controlled manner. Systems containing three different proportions of guar gum hydrogel and sesame oil were prepared, adding Span®60 or Span®60 and Tween®60 as surfactants. Drug and excipients were evaluated by cytotoxicity assays, showing no toxicity at the concentrations tested neither for the drug nor any of the excipients. Fresh formulations were characterised through texture analyses and confocal laser microcopy. The system with the lowest guar gum hydrogel/sesame oil proportion and containing Span®60 and Tween®60 (batch ST1) had the highest consistency and adhesion capacity according to texture analyses. Furthermore, a genuine bigel microstructure was observed. After freeze-drying, swelling, bioadhesion and drug release tests were performed on the resulting systems. ST1 showed the longest bioadhesion time and the most controlled release, as well as a low swelling grade, becoming an interesting option for preventing HIV sexual transmission in women.

The Effect of Small Doses of Fructose and Its Epimers on Glycemic Control: A Systematic Review and Meta-Analysis of Controlled Feeding Trials.

Objective: Contrary to the concerns that fructose may have adverse metabolic effects, an emerging literature has shown that small doses (≤10 g/meal) of fructose and its low-caloric epimers (allulose, tagatose, and sorbose) decrease the glycemic response to high glycemic index meals. Whether these acute reductions manifest as sustainable improvements in glycemic control is unclear. Our objective was to synthesize the evidence from controlled feeding trials that assessed the effect of small doses of fructose and its low-caloric epimers on glycemic control. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library through April 18, 2018. We included controlled feeding trials of ≥1 week that investigated the effect of small doses (≤50 g/day or ≤10% of total energy intake/day) of fructose and its low-caloric epimers on HbA1c, fasting glucose, and fasting insulin. Two independent reviewers extracted data and assessed risk of bias. Data were pooled using the generic inverse variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the Cochran Q statistic and quantified using the I² statistic. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessed the certainty of the evidence. Results: We identified 14 trial comparisons (N = 337) of the effect of fructose in individuals with and without diabetes, 3 trial comparisons (N = 138) of the effect of allulose in individuals without diabetes, 3 trial comparisons (N = 376) of the effect of tagatose mainly in individuals with type 2 diabetes, and 0 trial comparisons of the effect of sorbose. Small doses of fructose and tagatose significantly reduced HbA1c (MD = -0.38% (95% CI: -0.64%, -0.13%); MD = -0.20% (95% CI: -0.34%, -0.06%)) and fasting glucose (MD = -0.13 mmol/L (95% CI: -0.24 mmol/L, -0.03 mmol/L)); MD = -0.30 mmol/L (95% CI: -0.57 mmol/L, -0.04 mmol/L)) without affecting fasting insulin (p > 0.05). Small doses of allulose did not have a significant effect on HbA1c and fasting insulin (p > 0.05), while the reduction in fasting glucose was of borderline significance (p = 0.05). The certainty of the evidence of the effect of small doses of fructose and allulose on HbA1c, fasting glucose, and fasting insulin was graded as low. The certainty of the evidence of the effect of tagatose on HbA1c, fasting glucose, and fasting insulin was graded as moderate. Conclusions: Our results indicate that small doses of fructose and tagatose may improve glycemic control over the long term. There is a need for long-term randomized controlled trials for all four sugars to improve our certainty in the estimates.

Investigation of molecular mobility of pressure-sensitive-adhesive in oxybutynin patch in vitro and in vivo: Effect of sorbitan monooleate on drug release and patch mechanical property.

The aim of present study was to develop an oxybutynin (OXY) transdermal patch with good permeation behavior and mechanical property. Special attention was paid to the effect of chemical enhancer on the molecular mobility of pressure sensitive adhesive (PSA) at molecular level. PSAs and permeation enhancers were investigated through in vitro experiment using rat skin. The optimized formulation was evaluated through pharmacokinetic study using rat. In addition, the molecular mechanism of sorbitan monooleate (Span® 80) in the improvement of PSA molecular mobility was investigated using FT-IR, molecular dynamics simulation, DSC and rheological study. As a result, the optimized formulation using amide PSA demonstrated good adhesion property. And the AUC0-t and Cmax of optimized patch were 6435.8 ±â€¯747.8 h ∗ ng/mL and 127.8 ±â€¯18.0 ng/mL, respectively, which had no significant difference with commercial product. Furthermore, the improvement of the PSA mobility by Span® 80 rather than the decrease of interaction between drug and PSA was the main factor that enhanced the release of OXY from patch. In conclusion, a drug-in-adhesive OXY patch was developed, and the effect of PSA molecular mobility increase on the enhancement of drug skin permeation was proposed at molecular level.

Evaluation and optimization of pH-responsive niosomes as a carrier for efficient treatment of breast cancer.

Tamoxifen citrate (TXC) is commonly indicated to prevent cell multiplication and development of breast cancer. However, it is usually associated with limited activity and development of toxicity and resistance. This study aimed to describe an in situ pH-responsive niosomes as a carrier for localized and sustained delivery of TXC. The thin film hydration method was utilized to produce TXC niosomes using sorbitan monostearate and cholesterol of 1:1 Molar ratio. The produced formula displayed nano-spherical shape with entrapment efficiency (EE) of 88.90 ± 0.72% and drug release of 49.2 ± 1.51% within 8 h. This formula was incorporated into chitosan/glyceryl monooleate (CH/GMO) as a localized in situ pH-responsive hydrogel delivery system. Different formulae were produced by Design-Expert software based on user-defined response surface design utilizing different chitosan concentration (A) and GMO concentration (B) characterized for mean viscosity (R2) and in vitro release studies (R1). The results displayed that R1 was significantly antagonistic with both of A and B while R2 was significantly synergistic with both of them. The optimum formula was selected and capped with gold as an ideal candidate for computed tomography (CT) to evaluate the efficacy and tissue distribution of TXC utilizing Ehrlich carcinoma mice model. The optimum formula showed localized TXC in a tumour and consequently a significant anti-tumour efficacy compared with free TXC. Based on these outcomes, the novel in situ pH-responsive TXC-loaded noisome could be a promising formula for the efficient treatment of breast cancer.

Development and characterisation of chondroitin sulfate- and hyaluronic acid-incorporated sorbitan ester nanoparticles as gene delivery systems.

Glycosaminoglycans (GAGs) are natural polymers that are broadly used in gene delivery systems to increase stability as well as decrease toxicity and nonspecific interactions, thereby increasing transfection efficiency. In this work, we propose sorbitan ester-based lipid nanoparticles (SENS) functionalised with the GAGs chondroitin sulfate (CS) and hyaluronic acid (HA) as gene delivery systems. For this purpose, we describe the design and evaluation of these nanosystems loaded with plasmid DNA, including an evaluation of their physicochemical characteristics, stability properties, ability to protect and efficiently transfect cells with Enhanced Green Fluorescent Protein plasmid (pEGFP) in vitro, and biocompatibility both in vitro and in vivo. We confirm that molecules with high biological value and targeting potential, such as HA and CS, can be successfully incorporated into our recently developed sorbitan ester-based nanoparticles (SENS) and that this incorporation leads to effective stabilisation of both nanosystems as well as protects plasmid DNA. We demonstrated that the aforementioned incorporation of HA and CS enables long-term stability of the nanosystems in both liquid and lyophilised states, which is a remarkable property that can aid in their transfer to industry. The ability of these functionalised nanosystems to transfect the A549 cell line without compromising cell viability was also shown, as well as their innocuous safety profile in vivo. Thus, we provide valuable evidence of the suitable properties and potential of these hybrid nanoparticles as gene delivery systems.

Enhanced transdermal delivery with less irritation by magainin pore-forming peptide with a N-lauroylsarcosine and sorbitan monolaurate mixture.

Transdermal drug delivery is advantageous over other conventional drug administration routes. However, it can be inefficient because of the natural barrier of the stratum corneum which is the uppermost layer of the skin. A previous study verified that the treatment of magainin pore-forming peptide with N-lauroylsarcosine (NLS) on human skin can increase skin permeability by 47-fold. However, NLS is well known as a potential skin irritant. The irritation potential of NLS is known to decrease when mixed with sorbitan monolaurate (S20). Encouraged by these results, we combined S20 with magainin-NLS to enhance transdermal drug transport with less skin irritation. In this study, nine groups with magainin and NLS:S20 mixtures at different concentrations and weight fractions were screened to maximize their synergistic effect. To quantify the efficacy to toxicity ratio of each formulation, we defined the ratio as the "enhancement ratio/irritation potential (ER/IP)." The ER was observed by Franz cell diffusion of the target drug fluorescein, and the IP was measured by the cytotoxicity of the NIH/3T3 mouse fibroblast cell line. As a result, the magainin with the NLS:S20 mixture increased the permeability of porcine skin as well as decreased the toxicity. Among the various combinations, a formulation of 2% (w/v) NLS:S20 with a weight fraction of 0.6:0.4 had the largest ER/IP. ATR-FTIR spectroscopy of the formulations and skin was done to analyze the interactions in the formulations themselves and between the formulations and the skin. Both the intercellular lipidic route and transcellular route through the stratum corneum protein were involved in the delivery of fluorescein. This study turned pore-forming peptides into an efficient and safe penetration enhancer by combining them with other chemical penetration enhancers. Moreover, this discovery could be a possible method for enabling the transdermal delivery of macromolecules.

A comparison of two low-calorie sweeteners and sugar in dark chocolate on sensory attributes and emotional conceptualisations.

Reducing sugar consumption is an important aspect in the prevention of and fight against obesity. A broader understanding of consumers' perceptions of low-calorie sweeteners is needed. This study examined two low-calorie sweeteners, tagatose and stevia, in comparison to sugar in dark chocolate. A total of 219 consumers participated in this study and rated overall liking and sensory attributes. Participants also listed their emotional conceptualisations upon consumption and were assessed on emotional eating behaviour and health and taste attitudes. The chocolate with tagatose was perceived as more similar to the chocolate with sugar than with stevia on overall liking, texture, bitterness, duration of aftertaste and intensity of aftertaste. Furthermore, chocolate with sugar and chocolate with tagatose both elicited positive emotional conceptualisations whereas chocolate with stevia elicited negative emotional conceptualisations. In conclusion, dark chocolate with tagatose did not significantly differ from sugar in overall liking, most sensory attributes and emotional conceptualisation.

The in vivo transformation and pharmacokinetic properties of a liquid crystalline drug delivery system.

A liquid crystalline (LC) system, composed of phosphatidylcholine, sorbitan monoleate, and tocopherol acetate, was investigated to understand the in vivo transformation after subcutaneous injection, coupled with the physicochemical and pharmacokinetic properties of the formulation. The rat model was utilized to monitor a pseudo-time course transformation from a precursor LC formulation to the LC matrix, coupled with the blood concentration profiles of the formulations containing leuprolide acetate. Three formulations that result in the HII phase, demonstrating dissimilar in vitro release profiles, were used. The formulation showing the highest AUC, Cmax and Tmax, also displayed the greatest release rate in vitro, the lowest viscosity (LC matrix), and an earlier transformation (LC precursor to matrix) in vivo. A potential link between viscosity, phase transformation, and drug release properties of a liquid crystalline system is described.

Mechanistic insights of the enhancement effect of sorbitan monooleate on olanzapine transdermal patch both in release and percutaneous absorption processes.

In this paper, based on the optimized formulation of olanzapine (OLN) transdermal patch, the role of sorbitan monooleate (SP) in OLN release and percutaneous absorption processes was probed in vitro and in vivo. Rheological test, DSC, FT-IR and molecular modeling were conducted to elucidate the effect of SP on the release process of OLN from transdermal patch. Additionally, the action of SP on the percutaneous absorption process was probed using tape stripping transdermal experiment, confocal laser scanning microscopy (CLSM), ATR-FTIR and molecular docking. The results showed that the hydrogen bonding interaction between OLN and pressure sensitive adhesive (PSA) was weakened by SP, which resulted in a decrease in the cohesive interaction between polymer chains and an increase in the formation of free volume of PSA, thus, the release of OLN from patch was promoted. Meanwhile, the OH groups of SP interacted with the polar head groups of the ceramides, which increased the fluidity of the skin lipids, thereby improved the ability of OLN percutaneous absorption. In summary, this study demonstrated that not only the release but also the percutaneous absorption processes were promoted by SP. This study provided comprehensive molecular level understanding on the effect of penetration enhancer on transdermal patch and strategies for rationally selection of chemical enhancer for transdermal drug delivery systems.

Optimization of methotrexate loaded niosomes by Box-Behnken design: an understanding of solvent effect and formulation variability.

Dermal drug delivery system which localizes methotrexate (MTX) in the skin is advantageous in topical treatment of psoriasis. The aim of the current study was to understand dilution effects and formulation variability for the potential formation of niosomes from proniosome gels of MTX. Box-Behnken's design was employed to prepare a series of MTX proniosome gels of Span 40, cholesterol (Chol-X1) and Tween 20 (T20-X2). Short chain alcohols (X3), namely ethanol (Et), propylene glycol (Pg) and glycerol (G) were evaluated for their dilution effects on proniosomes. The responses investigated were niosomal vesicles size (Y1), MTX entrapment efficiency percent (EE%-Y2) and zeta potential (Y3). MTX loaded niosomes were formed immediately upon hydration of the proniosome gels with the employed solvents. Addition of Pg resulted in a decrease of vesicular size from 534 nm to 420 nm as Chol percentage increased from 10% to 30%, respectively. In addition, increasing the hydrophilicity of the employed solvents was enhancing the resultant zeta potential. On the other hand, using Et in proniosomal gels would abolish Chol action to increase the zeta potential value and hence less stable niosomal dispersion was formed. The optimized formula of MTX loaded niosomes showed vesicle size of 480 nm, high EE% (55%) and zeta potential of -25.5 mV, at Chol and T20 concentrations of 30% and 23.6%, respectively, when G was employed as the solvent. Hence, G was the solvent of choice to prepare MTX proniosomal gels with a maintained stability and highest entrapment.