Enhancement of the transdermal delivery of zidovudine by pretreating the skin with two physical enhancers: microneedles and sonophoresis

BackgroundZidovudine (AZT) has been the most widely used drug for antiretroviral therapy. In order to improve the therapy with this drug, different alternatives have been proposed, such as the transdermal administration. The use of permeation enhancers is necessary to favor the passage of this drug through the skin, due to its physicochemical properties and to the natural permeation barrier imposed by the skin. ObjectivesTo evaluate the effect of two permeation enhancers, sonophoresis and microneedles, on the permeability of AZT through the skin.MethodsPermeation studies with an AZT solution were performed using pigskin clamped in Franz-type cells. Sonophoresis was applied under different conditions (i.e., amplitude, duty cycle and application time), selected according to an experimental design, where the response variables were the increase in temperature of the skin surface and the increase in transepidermal water loss. ATR-FTIR was also used to demonstrate the effect of enhancers on membrane components. ResultsThe permeability of AZT through intact skin was very poor, with a very long lag time. Pretreatment of the skin with sonophoresis increased AZT transport significantly, reducing the lag time. The maximum flux (27.52 µgcm⁻² h⁻¹) and the highest total amount permeated (about 624 µg/cm²) were obtained when applying sonophoresis in continuous mode, with an amplitude of 20%, and an application time of 2 min. Sonophoresis appears to have an impact on stratum corneum proteins. The use of microneedles further increased the flux (30.41 µgcm⁻² h⁻¹) and the total amount permeated (about 916 µg/cm²), relative to sonophoresis. ConclusionThe results are encouraging in terms of promoting AZT transport through the skin using sonophoresis or microneedles as permeation enhancers.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s40199-021-00402-y.     

Phase transited asymmetric membrane floating nanoparticles: a means for better management of poorly water-soluble drugs

PurposeEffective remedy to gastrointestinal (GI) side effects caused by poorly water-soluble drugs remains a challenge. Researching for novel techniques to reduce these side effects and increase patient adherence to medical treatment is of interest. The current study aims to develop an innovative nano-sized gastro-retentive drug delivery for better management of poorly water-soluble drugs.MethodA non-disintegrating ibuprofen-asymmetric membrane floating nanoparticle (Ibuprofen-AMFNP) was prepared by phase inversion technique to increase the gastric residence of the drug. Powder characterization, solubility, in vitro buoyancy, effect on in vivo inflammatory markers, and polymer diffusibility studies were conducted on the prepared formulation. All UV-spectrophotometric analysis was accomplished through a fiber optic system.ResultsThe prepared Ibuprofen-AMFNPs were in the nano range of 114.45 nm ±1.31 nm. The formulation was buoyant for 12 h in the dissolution media indicating increased gastric residence, had better solubility and powder characteristics compared to the pure drug. Scanning electron microscopy revealed an outer non-porous and inner porous asymmetric membrane. Ibuprofen-AMFNP followed Higuchi drug release kinetics (p=0.9925) and had a Fickian diffusion release mechanism (n=0.05). Polymer diffusibility study showed that the 24 h stored formulation had faster drug release with no lag time (−923.08 nm/h) compared to a fresh formulation (2526.32 nm/h). The prepared nano-formulation showed a higher percentage of anti-inflammatory (85.144%) effect compared to the pure drug (78.336%).ConclusionIbuprofen-AMFNP is envisioned to help reduce drug-related GI side effects, improve drug delivery, and thereby increase patient adherence to medical treatment.Graphical abstract      

Nicotinamide-cinnamic acid cocktail exerts pancreatic β-cells survival coupled with insulin secretion through ERK1/2 signaling pathway in an animal model of apoptosis

PurposePancreatic β-cells protection is integral to insulin secretion in diabetic conditions. In this context, we investigated cinnamic acid in combination with nicotinamide on the regulation of insulin secretion and apoptosis in pancreatic β-cells using streptozotocin (STZ)-induced apoptotic model in vivo.MethodsThe pancreata of nicotinamide (NA)-cinnamic acid (CA) treated rats were studied using histopathological, immunofluorescence, molecular docking, and RT-PCR analyses, supported by serum glucose and insulin levels.ResultsThe biochemical data revealed that the acute treatment of NA and CA in combination significantly increased serum insulin, thereby lowering blood glucose level in vivo. From histological findings, NA-CA pre-treatment displayed significant protection against STZ-apoptotic trends, improved insulin secretion, and recapitulated the STZ-induced morphology to normal control. The upregulated expressions of caspases, caused by STZ-treatments, were significantly downregulated with NA-CA in immunofluorescent detection and their translational levels, respectively. We found dense ERK½-insulin staining and p-ERK½ expression, which was further supported by strong ERK½ residues-ligands interactions based on in silico analysis.ConclusionFrom the pre-clinical data, we thus conclude that NA-CA cocktail exerts dual insulin releasing and survival effects in pancreatic β-cells by targeting ERK½ pathway.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s40199-021-00412-w.     

Efficacy and expenses of succimer vs. d-penicillamine plus garlic in the treatment of lead poisoning: a retrospective cross-sectional study

PurposeLead Poisoning is a major health problem in Iran. We aimed to compare efficacy of a standard regimen (Succimer) with that of a low-priced combination of D-penicillamine and Garlic in outpatients with lead poisoning.MethodsIn this retrospective cross-sectional study, year-long clinical files of outpatients with lead poisoning in two referral toxicology clinics in Mashhad, Iran were reviewed. A total of 79 patients (all men), received either Succimer or a combination of D-penicillamen plus garlic (DPN + Gar), for 19 and 30 days, respectively. Clinical and laboratory data, including blood lead level (BLL), were analyzed and treatment expanses were compared between the two regimens.ResultsOf 79 male patients, 42 were treated by DPN + Gar and 37 received Succimer. Mean BLL of DPN + Gar group before treatment (965.73 ± 62.54 µg/L) was higher than that of the Succimer group (827.59 ± 24.41) (p < 0.001). After treatment, BLL in both groups significantly reduced to 365.52 ± 27.61 µg/L and 337.44 ± 26.34 µg/L, respectively (p < 0.001). The price of a 19-day treatment with Succimer was approximately 28.6 times higher than a one-month course of treatment with garlic plus DPN. None of the treatments caused serious side effects in the patients.ConclusionCombination therapy with DPN + Gar is as effective as Succimer in Pb poisoning, while treatment with Succimer is significantly more expensive.Graphical abstract      

Polyherbal combination for wound healing: Matricaria chamomilla L. and Punica granatum L.

BackgroundPunica granatum L. (pomegranate) with astringent activities and Matricaria chamomilla L. (chamomile) with anti-inflammatory and antioxidant properties are natural remedies used for various skin disorders, including wound healing.ObjectivesThis study was conducted to evaluate the individual and combined wound healing activity of the methanol extracts of pomegranate and chamomile flowers.MethodsAfter preparing the menthol fraction of pomegranate and chamomile flowers, the content of total phenols, total tannins, and total flavonoids of fractions was measured. For standardization of pomegranate and chamomile fractions, Gallic acid and apigenin-7-O-glucoside contents of them were determined using high-performance liquid chromatography (HPLC). Moreover, their antioxidant activities were examined using DPPH and FRAP tests. The antimicrobial assay was performed against Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. Three different concentrations of methanol fraction of each plant and one combination dose of fractions were investigated for their wound healing activities in an excision wound model on the rats’ dorsum. Finally, histopathological studies were done at the end of the experiment.ResultsPhytochemical examinations showed high amounts of phenolic compounds in pomegranate flowers, while chamomile flower fractions contained a high amount of total flavonoids. Both fractions, especially pomegranate, had potent antioxidant activity. The best results for wound closure were observed 7 days after wound induction. All treated groups exhibited superior wound contraction compared to their placebo at all measurement times. The combined form of pomegranate and chamomile had better wound healing properties compared to a single therapy, especially on time earlier to wound induction.ConclusionThis study represented high antioxidant and wound healing activities for methanol fraction of pomegranate and chamomile flowers, which could be related to their high content of phytochemicals. In comparison with single herb treatment, the combined form of these two fractions in lower concentrations accelerated wound closure.Graphical abstract      

Enhancement of transfection activity of lipoplexes by complexation with transferrin-bearing fusogenic polymer-modified liposomes

We previously developed complexes of lipoplexes containing 3beta-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol (DC-chol) and succinylated poly(glycidol)-modified liposome, which becomes fusogenic under weakly acidic condition, for use as a novel gene delivery system. This study explored the effect of lipoplex structures--the type of cationic lipid and cationic lipid/DNA charge ratio--on the transfection activity of those complexes. Three types of cationic lipid with different polar groups were used for the preparation of lipoplexes: DC-chol, N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP), and 3,5-dipentadecyloxybenzamidine (TRX-20) with dimethylamino group, trimethylammonium group, and benzamidine group, respectively. Complexation with the SucPG-modified transferrin-bearing liposomes affected transfection activity of these lipoplexes differently. The TRX-20 lipoplexes exhibited the most marked enhancement of transfection activity upon complexation with the SucPG-modified liposomes among these lipoplexes. The cationic lipid/DNA charge ratio of the lipoplex and the amount of the transferrin-bearing SucPG-modified liposomes associated to the lipoplex also affected the transfection activity of the resultant complexes. Highly potent gene vectors were obtained by adjusting these factors.     

Intravenous magnesium sulfate for prevention of vancomycin plus piperacillin-tazobactam induced acute kidney injury in critically ill patients: An open-label,placebo-controlled,randomized clinical trial

BackgroundRecent studies have shown an increased risk of acute kidney injury (AKI) induced by vancomycin + piperacillin-tazobactam (VPT) combination. In this study, the efficacy of intravenous magnesium sulfate in prevention of VPT induced AKI in critically ill patients admitted to the ICU has been evaluated.MethodsIn an open-label, placebo-controlled, randomized clinical trial, 72 adults (≥ 18 years old) who had indications to receive VPT as empiric therapy were assigned to the magnesium or control group in 1:1 ratio. Concomitant with VPT, intravenous infusion of magnesium sulfate was started for patients in the magnesium group. The target serum level of magnesium was defined 3 mg/dl. Patients in the control group received normal saline as placebo. The target serum level of magnesium was defined 1.9 mg/dl in this group. The study’s primary outcome was incidence of AKI during and up to 48 h after the treatment course. Escalation and de-escalation of VPT regimen, duration of hospitalization, length of ICU stay and 28-day mortality were secondary outcomes.ResultsThirty patients in each group completed the examination. Five patients in the magnesium group and 11 patients in the control group experienced AKI (p = 0.072). De-escalation of VPT regimen was done approximately in 60% of patients. Duration of hospitalization and length of ICU stay were not statistically different between the groups. Finally, 28-day mortality was 23.33% in each group. Although the incidence of AKI was not statistically different between the groups in unadjusted logistic regression model, it became significant after adjusting for confounding factors [unadjusted model (OR = 0.34; 95% CI: 0.10–1.16, p = 0.084), adjusted model: (OR = 0.26; 95% CI: 0.07–0.96, p = 0.04)].ConclusionsAdministration of magnesium sulfate with the target serum levels around 3 mg/dL reduced the incidence of AKI in critically ill patients who were receiving VPT as empric therapy.Graphical abstract      

An Insilico evaluation of phytocompounds from Albizia amara and Phyla nodiflora as cyclooxygenase-2 enzyme inhibitors

PurposeThe enzyme Cyclooxygenases (COX-1 and COX-2) catalyze the formation of prostaglandin, a mediator of the inflammatory pathway. Inflammation related pathological conditions may be alleviated by targeting the Cox enzymes.COX-2 inhibitors that are currently available in the market causes undesirable side effects. Our present study focuses on the in-silico inhibition of COX -2 enzyme by the phytocompounds from Albizia amara and Phyla nodiflora.MethodsThe phytochemicals present in Albizia amara and Phyla nodiflora were analyzed for their COX-2 inhibition potential. Eight compounds from Albizia amara and eleven compounds from Phyla nodiflora obtained from GC–MS analysis was used for the current study. Molecular docking was performed using AutoDock vina. The crystal structure of COX-2 (PDB ID: 5IKR) was obtained from Protein data bank. PyMol was used to remove any solvent, organic and inorganic molecules. Energy minimization of the protein was carried out using SPDBV software. Geometrical optimizations of the ligands were performed using Avogadro software. Celecoxib was used as the positive control. ADMET properties of the compounds were analyzed using SwissADME and ProtoxII online servers. Molecular mechanics/generalized born surface area (MM/GBSA) calculations were performed to evaluate the binding efficiency. Molecular dynamics of the protein and protein–ligand complex was studied for about 100 ns using Desmond package of Schrodinger suite.ResultsAmong the eighteen compounds, Squalene present in both the plants showed a better binding energy of -7.7 kcal/mol, when compare to other phytocompounds present in the extract. The control celecoxib showed a binding energy of about – 9.4 kcal/mol. The toxicity and ADMET properties of squalene indicated that it is non-toxic and followed Lipinski’s rule. Molecular Dynamics (MD) analysis showed that the binding of squalene to the enzyme was stable.ConclusionSqualene could potentially inhibit COX2 and o wing to its properties, squalene can be formulated in gels/creams and could be possibly used for external edema and inflammationGraphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s40199-021-00408-6.     

RP-HPLC method validation for fast extraction and quantification of Levonorgestrel drug from silicone based intrauterine device intended for in-process and finished formulation

BackgroundTo develop and validate a simple and consistent reversed phase high performance liquid chromatography (RP-HPLC) method for the estimation of Levonorgestrel (LNG) drug from silicone based intrauterine device.MethodsSample solution was prepared using tetrahydrofuran (THF) as solvent for the drug extraction, and RP-HPLC analysis was performed using Luna C18 analytical column (150 × 4.6 mm, 5 μm, 100 Å – Phenomenex), with a mobile phase consisting of a mixture of acetonitrile and water (50:50, v/v) at a flow rate of 1.0 ml/min and injection volume of 20 μl. Detection was carried out at 241 nm in PDA detector, with a total run time of 15 min. The method was validated in accordance with ICH guidelines. Method applicability was tested for optimizing formulation using quality-by-design approach, to check the stability and content uniformity of levonorgestrel-silicone mixture (core blend), and quantifying the amount of LNG from commercially available silicone based formulation.ResultsThe retention time for LNG drug was obtained at 8.5 min (± 0.3 min). A linear relationship was observed over the concentration range of 2.6–15.6 μg/ml with the correlation coefficient (r) value 0.9999. The method was found to be precise within the acceptable limit (RSD < 2%) and the drug recovery from the intrauterine device was found in the range 99.78–100.0%. Content uniformity for different prototypes developed was observed in the range of 91.6–101.4%, and assay of optimized core blend was in the range of 97.78–106.79% during the 10 days of retention period for stability studies.ConclusionThe validated method is found to be a simple, accurate, precise, reproducible, and hence can be used for the routine analysis of LNG such as in-process, quality control and stability assays of silicone based intrauterine devices by RP-HPLC.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s40199-021-00396-7.     

Evaluation of hepatic CYP2D1 activity and hepatic clearance in type I and type II diabetic rat models,before and after treatment with insulin and metformin

IntroductionConversion in the metabolism of drugs occurs in diabetes mellitus. Considering the importance of metabolic enzymes’ activities on the efficacy and safety of medicines, the changes in liver enzymatic activity of CYP2D1 and its related hepatic clearance, by using Dextromethorphan as probe in the animal model of type I and type II diabetes, before and after treatment, was assessed in this study.MethodsMale Wistar rats were randomly divided into 6 groups. Seven days after induction of diabetes type I and type II, treatment groups were received insulin and metformin daily for 14 days, respectively. In day 21, rats were subjected to liver perfusion by Krebs-Henseleit buffer containing Dextromethorphan as CYP2D1 probe. Perfusate samples were analyzed by HPLC fluorescence method in order to evaluate any changes in CYP2D1 activity.ResultsThe average metabolic ratio of dextromethorphan and hepatic clearance were changed from 0.012 ± 0.004 and 6.3 ± 0.1 in the control group to 0.006 ± 0.0008 and 5.2 ± 0.2 in the untreated type I diabetic group, and 0.008 ± 0.003 and 5.0 ± 0.6 in the untreated type II diabetic rats. Finally, the mean metabolic ratio and hepatic clearance were changed to 0.008 ± 0.001 and 5.4 ± 0.1, and 0.013 ± 0.003 and 6.1 ± 0.4 in the treated groups with insulin and metformin, respectively.ConclusionIn type I diabetic rats, corresponding treatment could slightly improve enzyme activity, whereas the hepatic clearance and enzyme activity reached to the normal level in type II group. Graphical abstractOpen in a separate window.     

Comparison of diclofenac with apigenin-glycosides rich Clinacanthus nutans extract for amending inflammation and catabolic protease regulations in osteoporotic-osteoarthritis rat model

BackgroundOsteoporotic-osteoarthritis is an incapacitating musculoskeletal illness of the aged.ObjectivesThe anti-inflammatory and anti-catabolic actions of Diclofenac were compared with apigenin-C-glycosides rich Clinacanthus nutans (CN) leaf extract in osteoporotic-osteoarthritis rats.MethodsFemale Sprague Dawley rats were randomized into five groups (n = 6). Four groups were bilateral ovariectomised for osteoporosis development, and osteoarthritis were induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee joints. The Sham group was sham-operated, received saline injection and deionized drinking water. The treatment groups were orally given 200 or 400 mg extract/kg body weight or 5 mg diclofenac /kg body weight daily for 28 days. Articular cartilage and bone changes were monitored by gross and histological structures, micro-CT analysis, serum protein biomarkers, and mRNA expressions for inflammation and catabolic protease genes.ResultsHPLC analysis confirmed that apigenin-C-glycosides (shaftoside, vitexin, and isovitexin) were the major compounds in the extract. The extract significantly and dose-dependently reduced cartilage erosion, bone loss, cartilage catabolic changes, serum osteoporotic-osteoarthritis biomarkers (procollagen-type-II-N-terminal-propeptide PIINP; procollagen-type-I-N-terminal-propeptide PINP; osteocalcin), inflammation (IL-1β) and mRNA expressions for nuclear-factor-kappa-beta NF-κβ, interleukin-1-beta IL-1β, cyclooxygenase-2; and matrix-metalloproteinase-13 MMP13 activities, in osteoporotic-osteoarthritis rats comparable to Diclofenac.ConclusionThis study demonstrates that apigenin-C-glycosides at 400 mg CN extract/kg (about 0.2 mg apigenin-equivalent/kg) is comparable to diclofenac in suppressing inflammation and catabolic proteases for osteoporotic-osteoarthritis prevention. Open in a separate windowGraphical abstractElectronic supplementary materialThe online version of this article (10.1007/s40199-020-00343-y) contains supplementary material, which is available to authorized users.     

Chromone–lipoic acid conjugate: Neuroprotective agent having acceptable butyrylcholinesterase inhibition,antioxidant and copper-chelation activities

PurposeAlzheimer’s disease (AD) is a multifaceted neurodegenerative disease. To target simultaneously multiple pathological processes involved in AD, natural-origin compounds with unique characteristics are promising scaffolds to develop novel multi-target compounds in the treatment of different neurodegenerative disease, especially AD. In this study, novel chromone-lipoic acid hybrids were prepared to find a new multifunctional lead structure for the treatment of AD.MethodsChromone-lipoic acid hybrids were prepared through click reaction and their neuroprotection and anticholinesterase activity were fully evaluated. The anti-amyloid aggregation, antioxidant and metal-chelation activities of the best compound were also investigated by standard methods to find a new multi-functional agent against AD.ResultsThe primary biological screening demonstrated that all compounds had significant neuroprotection activity against H2O2-induced cell damage in PC12 cells. Compound 19 as the most potent butyrylcholinesterase (BuChE) inhibitor (IC50 = 7.55 μM) having significant neuroprotection activity as level as reference drug was selected for further biological evaluations. Docking and kinetic studies revealed non-competitive mixed-type inhibition of BuChE by compound 19. It could significantly reduce formation of the intracellular reactive oxygen species (ROS) and showed excellent reducing power (85.57 mM Fe+2), comparable with quercetin and lipoic acid. It could also moderately inhibit Aβ aggregation and selectively chelate with copper ions in 2:1 M ratio.ConclusionCompound 19 could be considered as a hopeful multifunctional agent for the further development gainst AD owing to the acceptable neuroprotective and anti-BuChE activity, moderate anti-Aβ aggregation activity, outstanding antioxidant activity as well as selective copper chelation ability.Graphical abstractOpen in a separate windowA new chromone–lipoic acid hybrid was synthesized as anti-Alzheimer agent with BuChE inhibitory activity, anti-Aβ aggregation, metal-chelation and antioxidant properties.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40199-020-00378-1.     

Eremantholide C from aerial parts of Lychnophora trichocarpha,as drug candidate: fraction absorbed prediction in humans and BCS permeability class determination

BackgroundLychnophora trichocarpha (Spreng.) Spreng. ex Sch.Bip has been used in folk medicine to treat pain, inflammation, rheumatism and bruises. Eremantholide C, a sesquiterpene lactone, is one of the substances responsible for the anti-inflammatory and anti-hyperuricemic effects of L. trichocarpha.ObjectivesConsidering the potential to become a drug for the treatment of inflammation and gouty arthritis, this study evaluated the permeability of eremantholide C using in situ intestinal perfusion in rats. From the permeability data, it was possible to predict the fraction absorbed of eremantholide C in humans and elucidate its oral absorption process.MethodsIn situ intestinal perfusion studies were performed in the complete small intestine of rats using different concentrations of eremantholide C: 960 μg/ml, 96 μg/ml and 9.6 μg/ml (with and without sodium azide), in order to verify the lack of dependence on the measured permeability as a function of the substance concentration in the perfusion solutions.ResultsEremantholide C showed P_eff values, in rats, greater than 5 × 10⁻⁵ cm/s and fraction absorbed predicted for humans greater than 85%. These results indicated the high permeability for eremantholide C. Moreover, its permeation process occurs only by passive route, because there were no statistically significant differences between the P_eff values for eremantholide C.ConclusionThe high permeability, in addition to the low solubility, indicated that eremantholide C is a biologically active substance BCS class II. The pharmacological activities, low toxicity and biopharmaceutics parameters demonstrate that eremantholide C has the necessary requirements for the development of a drug product, to be administered orally, with action on inflammation, hyperuricemia and gout.Graphical abstract      

Anionic polymer-coated lipoplex for safe gene delivery into tumor by systemic injection

Abstract

In this study, we developed an anionic lipoplex by coating cationic lipoplex with anionic polymers such as hyaluronan (HA), chondroitin sulfate C (CS) and poly-l-glutamic acid (PLE) to deliver the plasmid DNA efficiently into the tumor by avoiding interaction with erythrocytes. The sizes of HA-, CS- and PLE-coated lipoplexes were ～200?nm and the ζ-potentials were negative. CS- and PLE-coated lipoplexes did not induce agglutination after mixing with erythrocytes, but cationic and HA-coated lipoplexes exhibited agglutination. In terms of biodistribution and gene expression after intravenous administration, cationic and HA-coated lipoplexes largely accumulated and induced gene expression in the lung. In contrast, CS- and PLE-coated lipoplexes did not exhibit high gene expression in the lung and mainly accumulated in the liver. However, in tumor, differences in lipoplex accumulation and gene expression were not observed among the lipoplexes. In terms of toxicity after intravenous injection, CS- and PLE-coated lipoplexes did not increase tumor necrosis factor-α, aspartate aminotransferase and alanine aminotransferase concentrations in blood. From these findings, CS and PLE coatings for cationic lipoplex might produce safe systemic vectors, although they did not increase gene expression in tumor.     

Design & development of nanosponge loaded topical gel of curcumin and caffeine mixture for augmented treatment of psoriasis

BackgroundCombination of curcumin with anti-inflammatory drug like caffeine shows augmented antipsoriatic action compared to curcumin alone and reduce the time taken for treatment of Psoriasis.ObjectiveThe objective of the present study was to develop nanosponge (NS) based topical gel of curcumin (CUR) and caffeine (CFN) combination that acts as a potential system for the treatment of psoriasis.MethodsNS composed of dimethyl carbonate (DMC) as crosslinker and beta-cyclodextrin (β-CD) as polymer were prepared by hot melt method and incorporated in topical gels. Factorial design (3²) was constructed in a fully randomized manner to study all nine possible experimental runs. The gels were prepared by varying the content of carbopol-934 (gelling agent) (X1) and guar gum (polymer) (X2). The effect of these two independent variables on viscosity (Y1) and in vitro percent drug release (Y2) of prepared gels was evaluated. Other evaluation studies for NS and nanogels were conducted. In vivo animal studies were carried out for optimized formulation using mouse model of imiquimod-induced psoriasis.ResultsThe physical and chemical characteristics exhibited by the prepared NS and gels (F1-F9) were found to be optimal. The optimization resulted in achieving formulation N10 with 69.72% in vitro drug release and 12,329.78cp viscosity. Histopathology studies revealed that prepared nanogel has promising anti-psoriatic activity. The results concluded that CUR and CFN combination has reduced the time required for showing anti-psoriatic activity to 10 days when compared to CUR alone that took around 20 days. Moreover, the nanogel has depicted sustained drug release till 12 h.ConclusionsFrom the experimental findings it has been concluded that CUR and CFN combination significantly augmented the anti-psoriatic efficacy with respect to individual components and also reduced the time required for onset of effect. Thus, the proposed nanogel would be an imperative drug delivery system for more effective anti-psoriatic therapy. Open in a separate windowGraphical abstract     

Safety of English ivy (Hedera helix) leaf extract during pregnancy: retrospective cohort study

BackgroundEnglish ivy (Hedera helix) is commonly used to reduce productive cough symptoms by acting as expectorant therapy. The safety of Hedera helix extract during pregnancy was not established yet. This study aims to determine the safety of English ivy leaf extract on newborns.ObjectivesTo determine the weight, APGAR (Activity-Pulse-Grimace-Appearance-Respiration) score, and health status of the newborns among the studied groups.MethodsA retrospective multicenter cohort study was conducted during the fourth quarter of 2020 on 245 pregnant women and their newborns in two hospitals located in Riyadh, Saudi Arabia. The women were divided into an exposed group (N = 165) who used English ivy leaf extract syrup during pregnancy, and a control group (N = 80) who were not using any natural-pharmaceutical product for cough.ResultsThe mean weight of the newborns in the exposed group was 3 kg compared to 2.8 kg in the control group (p-value < 0.05). The median APGAR score of the newborns in the exposed group was 8.5/10 compared to 8.0/10 in the control group (p-value > 0.05). There were no significant differences regarding the percentages of full-term and preterm newborns in the exposed and control groups (78.8% vs. 76.3%, and 21.0% vs. 24.0%, respectively, odds ratio [OR] = 0.86, 95% confidence interval [CI] = 0.45–1.63, p-value > 0.05). Regarding the newborns’ health complications reported, there was no statistical difference in the percentages of full-term newborns diagnosed with at least one health complication between the exposed and control groups (0.6 vs. 3.8, OR = 0.15, 95% CI = 0.01–1.47, p-value > 0.05).ConclusionHedera helix (English ivy) leaf extract syrup was safe to be used in short term during pregnancy for the fetus.Graphical abstract Keyword: English ivy, Hedera helix leaf extract, Hederacoside C, Pregnancy, Newborns     

Bioadhesive hydrogel comprising bilirubin/β-cyclodextrin inclusion complexes promote diabetic wound healing

ContextChronic non-healing diabetic wound therapy is an important clinical challenge. Manipulating the release of bioactive factors from an adhesive hydrogel is an effective approach to repair chronic wounds. As an endogenous antioxidant, bilirubin (BR) has been shown to promote wound healing. Nonetheless, its application is limited by its low water solubility and oxidative degradation.ObjectiveThis study developed a bilirubin-based formulation for diabetic wound healing.Materials and methodsBilirubin was incorporated into β-CD-based inclusion complex (BR/β-CD) which was then loaded into a bioadhesive hydrogel matrix (BR/β-CD/SGP). Scratch wound assays were performed to examine the in vitro pro-healing activity of BR/β-CD/SGP (25 μg/mL of BR). Wounds of diabetic or non-diabetic rats were covered with BR or BR/β-CD/SGP hydrogels (1 mg/mL of BR) and changed every day for a period of 7 or 21 days. Histological assays were conducted to evaluate the in vivo effect of BR/β-CD/SGP.ResultsCompared to untreated (18.7%) and BR (55.2%) groups, wound closure was more pronounced (65.0%) in BR/β-CD/SGP group. In diabetic rats, the wound length in BR/β-CD/SGP group was smaller throughout the experimental period than untreated groups. Moreover, BR/β-CD/SGP decreased TNF-α levels to 7.7% on day 3, and elevated collagen deposition and VEGF expression to 11.9- and 8.2-fold on day 14. The therapeutic effects of BR/β-CD/SGP were much better than those of the BR group. Similar observations were made in the non-diabetic model.Discussion and conclusionBR/β-CD/SGP promotes wound healing and tissue remodelling in both diabetic and non-diabetic rats, indicating an ideal wound-dressing agent.     

Comparing the cost,glycaemic control and medication adherence of utilizing patients’ own medicines (POMs) versus usual dispensing among diabetic patients in an outpatient setting

BackgroundMillions worth of unused drugs particularly those indicated for chronic diseases such as diabetes were returned and disposed leading to substantial wastage. Use of patients’ own medications (POMs) in the inpatient setting has reduced wastage and saved cost. The impact of utilizing POMs in the outpatient setting has hitherto not been determined.PurposeThis study aims to compare the cost, medication adherence and glycaemic control of utilizing POMs versus usual dispensing.MethodsProspective randomized controlled study was conducted among diabetic patients that required monthly medication refill in the Outpatient Pharmacy in 2017. Patients who consented were equally divided into POMs and control groups. Both groups brought excess medications from home at week-0 and week-12. Patients in the POMs group brought excess medications monthly and sufficient amount of drugs were added until the next refill date. Drugs were dispensed as usual in the control group. Total cost consisting of the cost of drugs, staff and building was calculated. Glycosylated haemoglobin (HbA1c) was measured at baseline and week-12. Adherence was measured based on pill counting.ResultsThirty patients aged 56.77 ± 14.67 years with 13.37 ± 7.36 years of diabetes participated. Baseline characteristics were similar between the groups. POMs minimized the total cost by 38.96% which translated to a cost saving of USD 42.76 ± 6.98, significantly different versus USD 0.02 ± 0.52 in the control group, p = 0.025. Mean HbA1c reduced significantly (−0.79%, p = 0.016) in the POMs group but not significant in the control group (−0.11%, p = 0.740). Medication adherence improved significantly in both groups at week-12 (p < 0.010). Nevertheless, patients in the POMs group were more adherent, 87.20% vs. 66.32%, p = 0.034.ConclusionUtilizing POMs resulted in cost saving, improved adherence and better glycaemic control. Use of POMs should be practiced in the outpatient pharmacy to reduce wastage and cost.Graphical abstract      

Evolution of a Compact Photoprobe for the Dopamine Transporter Based on (±)-threo-Methylphenidate

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