467 research outputs found
Star-shaped poly(oligoethylene glycol) copolymer-based gels: thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery
No full textThe aim of this work was to obtain an intranasal delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the delivery of risedronate (RS). For this, novel in situ forming gels comprising thermo-responsive star-shaped polymers, utilizing either polyethylene glycol methyl ether (PEGMA-ME 188, Mn 188) or polyethylene glycol ethyl ether (PEGMA-EE 246, Mn 246), with polyethylene glycol methyl ether (PEGMA-ME 475, Mn 475), were synthesized and characterized. RS was trapped in the selected gel-forming solutions at a concentration of 0.2% w/v. The pH, rheological properties, in vitro drug release, ex vivo permeation as well as mucoadhesion were also examined. MTT assays were conducted to verify nasal tolerability of the developed formulations. Initial in vivo studies were carried out to evaluate anti-osteoporotic activity in a glucocorticoid induced osteoporosis model in rats. The results showed successful development of thermo-sensitive formulations with favorable mechanical properties at 37°C, which formed non-irritant, mucoadhesive porous networks, facilitating nasal RS delivery. Moreover, sustained release of RS, augmented permeability and marked anti-osteoporotic efficacy as compared to intranasal (IN) and intravenous (IV) RS solutions were realized. The combined results show that the in-situ gels should have promising application as nasal drug delivery systems
Early Cretaceous (Aptian-Albian) palynology of the Kabrit-1 borehole, onshore Northern Gulf of Suez, Egypt
No full textIn situ composite ion-triggered gellan gum gel incorporating amino methacrylate copolymer microparticles: a therapeutic modality for buccal applicability
No full textThe aim of the current investigation is to delineate the buccal applicability of an in situ composite gel containing aceclofenac (AC) amino methacrylate copolymer microparticles (MPs), surmounting limitations of oral existing conventional therapy. AC Eudragit RL100 MPs were fabricated and statistically optimized using 2241 factorial design. Better buccal applicability and enhanced localization were achieved by combining the optimum MPs with in situ ion-activated gellan gum gel. The crosslinking and gelation of in situ gel were investigated by morphological and solid state characterizations. Suitability for buccal delivery and in vivo therapeutic efficacy in inflammation model of rats were also assessed. Results showed that the best performing formula displayed particle size (PS) of 51.00 μm and high entrapment efficiency (EE%) of 94.73%. MPs were successfully entrapped inside the gel network of the composite system. Gelation tendency, pH, shear-thinning properties and mucoadhesivity of the prepared in situ composite gel guaranteed its buccal suitability. Sustained AC release features and promising in vitro anti-arthritic response were also demonstrated. Moreover, consistent and prolonged in vivo anti-inflammatory effect was achieved, relative to standard AC. Taken together; this study proves the potential of in situ composite gel as an appropriate therapeutic proposal for AC buccal delivery
Biocompatibility, biodegradation and biomedical applications of poly(lactic acid)/poly(lactic-co-glycolic acid) micro and nanoparticles
No full textGamma oryzanol loaded into micelle-core/chitosan-shell: from translational nephroprotective potential to emphasis on sirtuin-1 associated machineries
No full textGamma oryzanol (ORZ) is a nutraceutical that is poorly water soluble with poor intestinal absorption. In the current work, ORZ was nanoformulated into uncoated and chitosan coated micelles based on methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) and poly(ε-caprolactone)-b-methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (PCL-PEG-PCL) copolymers for augmenting ORZ oral delivery. The physicochemical properties, morphological study, in-vitro release and safety of the nanoplaforms were determined. Importantly, the nephroprotective competence of the nanoplaforms was analyzed against acute kidney injury (AKI) rat model and the sirtuin-1 associated machineries were assessed. The results revealed that the micelles exerted particle size (PS) from 97.9 to 117.8 nm that was markedly increased after chitosan coating. The reversal of zeta potential from negative to highly positive further confirmed efficient coating. In vitro release profiles demonstrated prolonged release pattern. The nanoforms conferred higher cell viability values than free ORZ on Vero cell line. The designed micelles displayed augmented nephroprotection compared to free ORZ with the supremacy of CS coated micelles over uncoated ones in restoring kidney parameters to normal levels. The attenuated AKI was fulfilled via the modulation of sirtuin-1 signaling pathways translated by restoring the histological features, increasing renal antioxidant states, renal autophagy and decreasing renal inflammation and renal apoptosis. These outcomes confirmed that surface modification with chitosan had a considerable leverage on micelles safety, release behavior and in vivo performance
Exploring optimized methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) crystalline cored micelles in anti-glaucoma pharmacotherapy
No full textMethoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) polymeric micelles (PMs) open a promising avenue through which ocular drug delivery with superior efficacy and tolerability can be potentially obtained. Methazolamide (MTZ) is an anti-glaucoma drug exhibiting poor corneal penetration, making it an ideal candidate for new polymeric micellar systems. MTZ-PMs were prepared using the thin film hydration procedure and optimized using a Design of Experiment (DoE) approach. In vitro drug release, thermal analyses and FT-IR characterization were also evaluated. MTT assay and histopathological assessment were carried out to verify ocular tolerability as well as Draize irritancy test. In vivo studies were conducted on rabbits to evaluate anti-glaucoma activity in a glucocorticoid-induced glaucoma model. The results showed successful entrapment of MTZ inside PMs matrix as reflected by the complete vanishing of drug melting peak in DSC thermogram and the possible formation of hydrogen bonding between MTZ and mPEG-PCL copolymer in FT-IR spectrum. The selected formula exhibited a particle size of 60 nm, entrapment efficiency of 93% and discrete spherical particles. Moreover, sustained release of MTZ, cellular and tissue biocompatibility and marked anti-glaucoma efficacy, as compared to MTZ solution, were realized. The combined results show that PMs could potentiate the therapeutic outcome of nanotechnology ocular drug delivery
Quercetin Loaded Monolaurate Sugar Esters-Based Niosomes: Sustained Release and Mutual Antioxidant-Hepatoprotective Interplay
No full textFlavonoids possess different interesting biological properties, including antibacterial, antiviral, anti-inflammatory and antioxidant activities. However, unfortunately, these molecules present different bottlenecks, such as low aqueous solubility, photo and oxidative degradability, high first-pass effect, poor intestinal absorption and, hence, low systemic bioavailability. A variety of delivery systems have been developed to circumvent these drawbacks, and among them, in this work niosomes have been selected to encapsulate the hepatoprotective natural flavonoid quercetin. The aim of this study was to prepare nanosized quercetin-loaded niosomes, formulated with different monolaurate sugar esters (i.e., sorbitan C12; glucose C12; trehalose C12; sucrose C12) that act as non-ionic surfactants and with cholesterol as stabilizer (1:1 and 2:1 ratio). Niosomes were characterized under the physicochemical, thermal and morphological points of view. Moreover, after the analyses of the in vitro biocompatibility and the drug-release profile, the hepatoprotective activity of the selected niosomes was evaluated in vivo, using the carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Furthermore, the levels of glutathione and glutathione peroxidase (GSH and GPX) were measured. Based on results, the best formulation selected was glucose laurate/cholesterol at molar ratio of 1:1, presenting spherical shape and a particle size (PS) of 161 ± 4.6 nm, with a drug encapsulation efficiency (EE%) as high as 83.6 ± 3.7% and sustained quercetin release. These niosomes showed higher hepatoprotective effect compared to free quercetin in vivo, measuring serum biomarker enzymes (i.e., alanine and aspartate transaminases (ALT and AST)) and serum biochemical parameters (i.e., alkaline phosphatase (ALP) and total proteins), while following the histopathological investigation. This study confirms the ability of quercetin loaded niosomes to reverse CCl4 intoxication and to carry out an antioxidant effect
Development and In Vivo Evaluation of Multidrug Ultradeformable Vesicles for the Treatment of Skin Inflammation
No full textThe aim of this work was to evaluate the effect of two chemically different edge activators, i.e., Tween® 80 and sodium deoxycholate, on (i) the physical, mechanical, and biological properties of ultradeformable vesicles, and (ii) the administration of naproxen sodium-loaded multidrug ultradeformable vesicles for the transdermal route in order to obtain therapeutically meaningful drug concentrations in the target tissues and to potentiate its anti-inflammatory effect by association with the antioxidant drug idebenone. The results obtained in this investigation highlighted a synergistic action between naproxen and idebenone in the treatment of inflammatory disease with a more pronounced anti-inflammatory effect in multidrug ultradeformable vesicles compared to the commercial formulation of Naprosyn® gel. Systems made up of Tween® 80 appeared to be the most suitable in terms of percutaneous permeation and anti-inflammatory activity due to the greater deformability of these vesicles compared to multidrug ultradeformable vesicles with sodium deoxycholate. Our findings are very encouraging and suggest the use of these carriers in the topical treatment of inflammatory diseases
The role of the angle of progression in the prediction of the outcome of occiput posterior position in the second stage of labor
No full textBackground: Occiput posterior position is the most frequent cephalic malposition, and its persistence at delivery is associated with a higher risk of maternal and perinatal morbidity. Diagnosis and management of occiput posterior position remain a clinical challenge. This is partly caused by our inability to predict fetuses who will spontaneously rotate into occiput anterior from those who will have persistent occiput posterior position. The angle of progression, measured with transperineal ultrasound, represents a reliable tool for the evaluation of fetal head station during labor. The relationship between the persistence of occiput posterior position and fetal head station in the second stage of labor has not been previously assessed. Objective: This study aimed to evaluate the role of fetal head station, as measured by the angle of progression, in the prediction of persistent occiput posterior position and the mode of delivery in the second stage of labor. Study Design: We recruited a nonconsecutive series of women with posterior occiput position diagnosed by transabdominal ultrasound in the second stage of labor. For each woman, a transperineal ultrasound was performed to measure the angle of progression at rest. We compared the angle of progression between women who delivered fetuses in occiput anterior position and those with persistent occiput posterior position at delivery. Receiver operating characteristics curves were performed to evaluate the accuracy of the angle of progression in the prediction of persistent occiput posterior position. Finally, we performed a multivariate logistic regression to determine independent predictors of persistent occiput posterior position. Results: Overall, 63 women were included in the analysis. Among these, 39 women (62%) delivered in occiput anterior position, whereas 24 (38%) delivered in occiput posterior position (persistent occiput posterior position). The angle of progression was significantly narrower in the persistent occiput posterior position group than in women who delivered fetuses in occiput anterior position (118.3°±12.2° vs 127.5°±10.5°; P=.003). The area under the receiver operating characteristics curve was 0.731 (95% confidence interval, 0.594–0.869) with an estimated best cutoff range of 121.5° (sensitivity of 72% and specificity of 67%). On logistic regression analysis, the angle of progression was found to be independently associated with persistence of occiput posterior position (odds ratio, 0.942; 95% confidence interval, 0.889–0.998; P=.04). Finally, women who underwent cesarean delivery had significantly narrower angle of progression than women who had a vaginal delivery (113.5°±8.1 vs 128.0°±10.7; P<.001). The area under the receiver operating characteristics curve for the prediction of cesarean delivery was 0.866 (95% confidence interval, 0.761–0.972). At multivariable logistic regression analysis including the angle of progression, parity, and gestational age at delivery, the angle of progression was found to be the only independent predictor associated with cesarean delivery (odds ratio, 0.849; 95% confidence interval, 0.775–0.0930; P<.001). Conclusion: In fetuses with occiput posterior at the beginning of the second stage of labor, narrower values of the angle of progression are associated with higher rates of persistent occiput posterior position at delivery and a higher risk of cesarean delivery
Noscapine loaded biodegradable nanoparticles to treat breast cancer
No full textBreast cancer is the most common malignancy in women
worldwide. Therapeutic strategies currently involve a
combination of surgery, radiotherapy, immunotherapy,
hormone therapy and/or chemotherapy. The efficacy of a
chemotherapeutic formulation depends on its ability to
selectively target diseased tissue, overcome biological
barriers, and intelligently respond to the disease
environment to release cytotoxic agents. The development
of a controlled and targeted drug delivery system may result
in a more efficient and less harmful solution to overcome
the limitations associated with conventional chemotherapy
(Cho et al.). Recent studies have been focused on
developing nanoscale delivery vehicles capable of
controlling the release of chemotherapeutics directly inside
cancer cells. Micellar like nanoparticles (NPs) are produced
by the self-assembly of amphiphilic molecules into a
structure with a hydrophobic core and an hydrophilic outer
layer, with diameters generally less than 100 nm, allowing
them to extravasate through the tumor vessels fenestrations.
Moreover, their hydrophilic surfaces may shield them from
immediate recognition by reticuloendothelial system (RES)
leading to an increase in their circulation time. Many
micellar formulations are currently under clinical evaluation
for the treatment of cancer (e.g. doxorubicin, paclitaxel and
epirubicin). Therefore, the aim of this study was to
synthesize a series of linear-block and star-shaped
copolymers based on polyethylene glycol (PEG) and
poly(ε-caprolactone) (PCL), and to formulate noscapine
(NOS) loaded biodegradable NPs by the nanoprecipitation
technique. After characterization of these NPs, the best
formulae were tested for in-vitro release and cytotoxicity
using MCF-7 breast cancer cells. Pharmacokinetic
parameters and NPs in-vivo toxicity were also tested to
assess whether these NPs, would have high half-life in
addition to their low cytotoxicity, enhancing NOS passive
targeting to cancer cells. In addition, the selective release of
NOS as an alkaloid in the acidic medium was tested to
mimic what would happen in the vicinity of cancer tissues
and this would increase NOS safety and efficacy during its
use as anti-cancer agent
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