Pullulan derivative with cationic and hydrophobic moieties as an appropriate macromolecule in the synthesis of nanoparticles for drug delivery.

A new amphiphilic pullulan derivative (DBAP-PO) was obtained by grafting tertiary butyl amine and octanoyl groups on the pullulan backbone as cationic and hydrophobic moieties, respectively. The structural characteristics of the modified polymer were investigated by FT-IR and 1H and 13C NMR spectroscopy. The self-association ability in aqueous solution of DBAP-PO was studied by viscosity and fluorescence methods. The intrinsic viscosity of the polymer was determined by Wolf model. The critical aggregation concentration (CAC) value of 0.028 g/dL, determined by fluorescence measurements in the presence of pyrene, was confirmed by capillary viscosimetry and dynamic laser scattering (DLS). Dialysis method was used to demonstrate the capacity of the pullulan derivative to form spherical nanoparticles (d ~ 200 nm) loaded with model drug, sodium diclofenac (DF) (74% entrapment efficiency). The DF release was sustained and pH-dependent. In vitro cytotoxicity as well as morphological studies conducted on the human skin fibroblasts showed that DBAP-PO/DF nanoparticles do not exhibit cytotoxic effects at the pharmacologically relevant concentration of DF, maintaining the typical morphology of the cells.

Effects of lecithin-based nanoemulsions on skin: Short-time cytotoxicity MTT and BrdU studies, skin penetration of surfactants and additives and the delivery of curcumin.

Surfactants are important ingredients in pharmaceutical and cosmetic formulations, as in creams, shampoos or shower gels. As conventional emulsifiers such as sodium dodecyl sulfate (SDS) have fallen into disrepute due to their skin irritation potential, the naturally occurring lecithins are being investigated as a potential alternative. Thus, lecithin-based nanoemulsions with and without the drug curcumin, known for its wound healing properties, were produced and characterised in terms of their particle size, polydispersity index (PDI) and zeta potential and compared to SDS-based formulations. In vitro toxicity of the produced blank nanoemulsions was assessed with primary human keratinocytes and fibroblasts using two different cell viability assays (BrdU and EZ4U). Further, we investigated the penetration profiles of the deployed surfactants and oil components using combined ATR-FTIR/tape stripping experiments and confirmed the ability of the lecithin-based nanoemulsions to deliver curcumin into the stratum corneum in tape stripping-UV/Vis experiments. All manufactured nanoemulsions showed droplet sizes under 250 nm with satisfying PDI and zeta potential values. Viability assays with human skin cells clearly indicated that lecithin-based nanoemulsions were superior to SDS-based formulations. ATR-FTIR tests showed that lecithin and oil components remained in the superficial layers of the stratum corneum, suggesting a low risk for skin irritation. Ex vivo tape stripping experiments revealed that the kind of oil used in the nanoemulsion seemed to influence the depth of curcumin penetration into the stratum corneum.

Dietary Polar Lipids and Cognitive Development: A Narrative Review.

Polar lipids are amphiphilic lipids with a hydrophilic head and a hydrophobic tail. Polar lipids mainly include phospholipids and sphingolipids. They are structural components of neural tissues, with the peak rate of accretion overlapping with neurodevelopmental milestones. The critical role of polar lipids in cognitive development is thought to be mediated through the regulation of signal transduction, myelination, and synaptic plasticity. Animal products (egg, meat, and dairy) are the major dietary sources of polar lipids for children and adults, whereas human milk and infant formula provide polar lipids to infants. Due to the differences observed in both concentration and proportion of polar lipids in human milk, the estimated daily intake in infants encompasses a wide range. In addition, health authorities define neither intake recommendations nor guidelines for polar lipid intake. However, adequate intake is defined for 2 nutrients that are elements of these polar lipids, namely choline and DHA. To date, limited studies exist on the brain bioavailability of dietary polar lipids via either placental transfer or the blood-brain barrier. Nevertheless, due to their role in pre- and postnatal development of the brain, there is a growing interest for the use of gangliosides, which are sphingolipids, as a dietary supplement for pregnant/lactating mothers or infants. In line with this, supplementing gangliosides and phospholipids in wild-type animals and healthy infants does suggest some positive effects on cognitive performance. Whether there is indeed added benefit of supplementing polar lipids in pregnant/lactating mothers or infants requires more clinical research. In this article, we report findings of a review of the state-of-the-art evidence on polar lipid supplementation and cognitive development. Dietary sources, recommended intake, and brain bioavailability of polar lipids are also discussed.

Liposomes containing biosurfactants isolated from Lactobacillus gasseri exert antibiofilm activity against methicillin resistant Staphylococcus aureus strains.

Staphylococcus aureus is the major causative agent of skin and soft tissue infections, whose prevention and treatment have become more difficult due to the emergence of antibiotic-resistant strains. In this regard, the development of an effective treatment represents a challenge that can be overcome by delivering new antibiofilm agents with appropriate nanocarriers. In this study, a biosurfactant (BS) isolated from Lactobacillus gasseri BC9 and subsequently loaded in liposomes (LP), was evaluated for its ability to prevent the development and to eradicate the biofilm of different methicillin resistant S. aureus (MRSA) strains. BS from L. gasseri BC9 was not cytotoxic and was able to prevent formation and to eradicate the biofilm of different MRSA strains. BS loaded liposomes (BS-LP) presented a mean diameter (lower than 200 nm) suitable for topical administration and a low polydispersity index (lower than 0.2) that were maintained over time for up 28 days. Notably, BS-LP showed higher ability than free BS to inhibit S. aureus biofilm formation and eradication. BS-LP were loaded in lyophilized matrices able to quickly dissolve (dissolution time lower than 5 s) upon contact with exudate, thus allowing vesicle reconstitution. In conclusion, in this work, we demonstrated the antibiofilm activity of Lactobacillus-derived BS and BS-LP against clinically relevant MRSA strains. Furthermore, the affordable production of lyophilized matrices containing BS-LP for local prevention of cutaneous infections was established.

Optimization and Evaluation of Beclomethasone Dipropionate Micelles Incorporated into Biocompatible Hydrogel Using a Sub-Chronic Dermatitis Animal Model.

The current study is concerned with the development and characterization of mixed micelles intended for the dermal delivery of beclomethasone dipropionate, which is a topical corticosteroid used in the management of atopic dermatitis. Mixed micelles were prepared using thin-film hydration technique, employing different concentrations of pluronic L121 with either poloxamer P84 or pluronic F127 with different surfactant mixture-to-drug ratios. The prepared formulae were characterized concerning entrapment efficiency, particle size, and zeta potential. Two formulae were chosen for ex vivo skin deposition studies: one formulated using pluronic L121/poloxamer P84 mixture while the other using pluronic L121/pluronic F127 mixture. The optimum formula with the highest dermal deposition was subjected to morphological examination and was formulated as hydroxypropyl methylcellulose hydrogel. The hydrogel was evaluated regarding viscosity and was subjected to ex vivo deposition study in comparison with the commercially available cream Beclozone®. In vivo histopathological study was conducted for both the hydrogel and Beclozone® in order to evaluate their healing efficiency. In vivo histopathological study results showed that the prepared hydrogel successfully treated sub-chronic dermatitis in an animal model within a shorter period of time compared to Beclozone®, resulting in better patient compliance and fewer side effects.

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.

Microemulsions based on TPGS and isostearic acid for imiquimod formulation and skin delivery.

Imiquimod (IMQ) is an immunostimulant drug topically used for the treatment of actinic keratosis and basal cell carcinoma. IMQ formulation and skin delivery is difficult because of its very low solubility in the most of pharmaceutical excipients and very poor skin penetration properties. The purpose of this study was to develop a microemulsion to optimize imiquimod skin delivery using d­α­tocopherol polyethylene glycol-1000 succinate (TPGS) as surfactant (so as to take advantage of its thickening properties) and isostearic acid as oil phase. This fatty acid was selected since it has demonstrated a good solubilizing power for imiquimod and it has also shown to contribute to its therapeutic activity. We have built pseudo-ternary diagrams using two different co-surfactants (Transcutol® and propylene glycol - PG) in a 1:1 ratio with TPGS and then selected microemulsions in the clear and viscous regions of the diagrams. The systems were characterized in terms of rheology and X-ray scattering; additionally, the capability to promote IMQ skin uptake was evaluated ex-vivo on a porcine skin model. All the formulations selected in the gel-microemulsion regions behaved as viscoelastic solids; X-rays scattering experiments revealed in all cases the presence of an ordered lamellar structure, but with differences in terms of interlamellar distance and flexibility between Transcutol® and PG-containing systems. A higher flexibility and a greater hydrophobic volume, possibly interconnected at some point, was associated to the use of Transcutol® and had an impact on the microemulsion capacity to solubilize IMQ as well as on the capability to enhance drug uptake into the skin. The best performing gel-like microemulsion was composed of ≈26% of water, ≈21% of isostearic acid, ≈26% of TPGS and ≈27% of Transcutol® and accumulated, after 6 h of contact, 3.0 ±â€¯1.1 µg/cm2 of IMQ. This value is higher than the one reported in the literature for the commercial cream (1.9 ±â€¯0.8 µg/cm2), despite the 4-times lower concentration of the vehicle (13 mg/g for the microemulsion vs 50 mg/g for the commercial cream).

[Resistance to vitamin K antagonist revealing interaction with soy lecithin]. / Résistance aux antivitamines K révélant une interaction avec la lécithine de soja.

Vitamin K antagonists (VKA) are difficult to use because of a narrow therapeutic index and of a marked inter- and intra-individual variability among patients in the required dosage. This drug may interact with many other drugs and same with certain food compounds. We report the case of potential interaction between soy lecithin and Vitamin K antagonists in a 46 years-old woman. Subtherapeutic INR values were detected despite the increase gradually in dose and replacing acenocoumarol by fluindione. An enquiry of pharmacovigilance was conducted found the consumption of soy lecithin capsules. Fifteen days after its stopping, the INR values have really increased. Clinicians should think to the possibility of interaction between oral anticoagulants and food supplement that is increasingly used.

Novel cremochylomicrons for improved oral bioavailability of the antineoplastic phytomedicine berberine chloride: Optimization and pharmacokinetics.

Berberine chloride (BER) is an antineoplastic phytomedicine that combat non-Hodgkin lymphoma. BER suffers from low oral bioavailability due to p-glycoprotein efflux and first-pass metabolism. Lymphatic drug targeting recently gained a profound attention due to circumventing hepatic first-pass metabolism and targeting lymph diseases. Therefore, novel BER-loaded cremochylomicrons were elaborated to mitigate BER drawbacks and enhance its lymphatic targeting and bioavailability. Optimized cremochylomicron was prepared with 2.5%w/v Cremophor El and 12.5% w/w berberine content. Promising in vitro characteristics (particle size = 175.6 nm and entrapment efficiency = 95.5%) were obtained. Lyophilized system showed high colloidal stability over 6 months. In addition in vivo pharmacokinetics study demonstrated significant enhancement (>2fold) in the rate and extent of absorption in cremochylomicron over free BER. Moreover, cremochylomicrons demonstrated in significant increase in mean residence time and volume of distribution with decreased intestinal drug clearance as a result of efflux inhibition. In another avenue, a significant reduction in BER absorption (43%) in presence of cycloheximide inhibitor was obtained confirming the lymphatic targeting ability of cremochylomicrons. In conclusion, berberine-loaded cremochylomicron could be considered as a promising nanoplatform for targeting lymphatic system and improving BER oral bioavailability with lower dose and side effects.

Incorporation of lipolysis in monolayer permeability studies of lipid-based oral drug delivery systems.

Lipid-based drug delivery systems, a well-tolerated class of formulations, have been evaluated extensively to enhance the bioavailability of poorly soluble drugs. However, it has been difficult to predict the in vivo performance of lipid dosage forms based on conventional in vitro techniques such as cell monolayer permeability studies because of the complexity of the gastrointestinal processing of lipid formulations. In the current study, we explored the feasibility of coupling Caco-2 and Madin-Darby canine kidney monolayer permeability studies with lipolysis, a promising in vitro technique to evaluate lipid systems. A self-emulsifying lipid delivery system was formulated using a blend of oil (castor oil), surfactant (Labrasol® or PL497), and co-surfactant (lecithin). Formulations demonstrating high drug solubility and rapid self-emulsification were selected to study the effect of lipolysis on in vitro cell permeability. Lipolysis of the formulations was carried out using pancreatin as the digestive enzyme. All the digested formulations compromised monolayer integrity as indicated by lowered trans-epithelial electrical resistance (TEER) and enhanced Lucifer yellow (LY) permeability. Further, the changes in TEER value and LY permeability were attributable to the digestion products of the formulation rather than the individual lipid excipients, drug, digestion enzyme, or the digestion buffer. The digested formulations were fractionated into pellet, oily phase, and aqueous phase, and the effect of each of these on cell viability was examined. Interestingly, the aqueous phase, which is considered important for in vivo drug absorption, was responsible for cytotoxicity. Because lipid digestion products lead to disruption of cell monolayer, it may not be appropriate to combine lipolysis with cell monolayer permeability studies. Additional in vivo studies are needed to determine any potential side effects of the lipolysis products on the intestinal permeability barrier, which could determine the suitability of lipid-based systems for oral drug delivery.

The efficacy of Poly-ß-Hydroxy Butyrate (PHB)/biosurfactant derived from Staphylococcus hominis against White Spot Syndrome Virus (WSSV) in Penaeus monodon.

White Spot Syndrome Virus (WSSV) is one of the most important causative agents of Penaeid shrimps diseases that incur heavy losses to the shrimp aquaculture. It has severe impact on the sustainability and the production of Penaeus monodon. Hence, the present study focussed on the investigation of Poly-ß-hydroxybutyrate/biosurfactant as immunostimulants against WSSV infected shrimps. Infection of WSSV was periodically checked in all the experimental shrimps using PCR diagnostic kit. After ensuring all shrimps were free of viral infection, experiments were carried out to analyze the nonspecific immune responses (prophenol oxidase, nitro blue tetrazolium reduction assay and total haemocyte count) both in control and experimental group. Further, gills and muscles of Penaeus monodon were subjected to proteome analysis after treated it with PHB/biosurfactant independently in the concentration of 2% and 5% each. Increase in the level of haemocytes was observed in both PHB (26 ± 2 × 104 cells)/biosurfactant (28 ± 2 × 104 cells) treated shrimps, when compared with control (17 ± 2 × 104 cells). proPhenolOxidase (proPO) activity was also enhanced in treated groups compared to WSSV infected shrimps. Less production of superoxide anion was observed in control and treated groups. Differences in the protein expression was analyzed in muscle tissue of control, WSSV infected and PHB/biosurfactant treated shrimps. Our finding suggested that partial substitution of feed with 2% PHB and biosurfactant showed increased rate on the survival of WSSV infected P. monodon which might be due to either the over expression/down regulation of proteins that play a vital role in enhancing the immune system/the progression of the disease respectively.

Association of Dissemination of an Educational Communication Tool With Docusate Administration.

Importance: A clear message and call to action can affect the use of a medication with limited efficacy. Objectives: To assess the association of the dissemination of an educational document about the lack of efficacy of docusate with docusate administration and whether changing docusate administration was associated with a change in administration of comparable laxatives. Design, Setting, and Participants: In this quasi-experimental, pre-post study of all acute care and continuing care facilities serviced by Alberta Health Services in Alberta, Canada, an interrupted time series analysis was performed to examine the association of an educational communication tool with docusate administration from June 1, 2014, through May 31, 2016. Interventions: A Drugs & Therapeutics Backgrounder was disseminated to all pharmacists in December 2014. Backgrounders are academic detailing tools to assist pharmacists in supporting drug stewardship and are supplemented by online, interactive webinars. Main Outcomes and Measures: This study examined whether a decrease in docusate administration across the organization occurred after release of the backgrounder. Messaging in the backgrounder stated that, unless clinically necessary, docusate should not be replaced by another medication. This study assessed whether that message was accepted by measuring administration of comparable laxatives. Study medication administration is reported as defined daily doses (DDDs) per 1000 inpatient-days (PDs). Rates were compared for the 6 months before the intervention and 3, 6, 12, and 18 months after intervention. Results: Among the 111 acute care facilities (8500 beds) and 24 000 long-term care beds of the Alberta Health Services, predicted docusate administration decreased from preintervention (474 DDDs/1000 PDs) to 3 months (321 DDDs/1000 PDs; 95% CI, 304-465 DDDs/1000 PDs), 6 months (296 DDDs/1000 PDs; 95% CI, 277-456 DDDs/1000 PDs), 12 months (251 DDDs/1000 PDs; 95% CI, 207-499 DDDs/1000 PDs), and 18 months (214 DDDs/1000 PDs; 95% CI, 148-536 DDDs/1000 PDs). Administration of the comparable laxatives did not statistically significantly change (preintervention: 627 DDDs/1000 PDs; 18 months after intervention: 702 DDDs/1000 PDs; 95% CI, 295-694 DDDs/1000 PDs; P = .13). Conclusions and Relevance: A communication document supported by live presentations was associated with decreased administration of docusate up to 6 months, with a leveling of the association after 1 year. Significant systemic change can be achieved without extensive and complex interventions if the evidence and messaging are aligned.

Nanosuspension-Based Aloe vera Gel of Silver Sulfadiazine with Improved Wound Healing Activity.

The present study focuses on the development and characterization of nanosuspension of a poorly soluble drug, silver sulfadiazine (SSD) incorporated in Aloe vera gel (AV-gel) for improving its therapeutic efficacy. The SSD solution in ammonia was subjected to nanoprecipitation in surfactant solution and particle size was optimized by varying concentration of surfactant. Optimized formulation constituted of 5.5% (w/v) Span 20 and 5.5% (w/v) Tween 80 as a dispersing agent and 0.5% (w/v) Poloxamer 188 as a co-surfactant. The prepared nanosuspension was evaluated for particle size, polydispersity index, surface morphology, and x-ray diffraction study. The optimized nanosuspension was incorporated into nanogel formulation with the addition of 1% AV-gel and 0.5% Carbopol 940 for topical delivery of nanosized SSD. Evaluation of in vitro drug release exhibited a significant enhancement in release rate of the drug from developed nanogel formulation (77.16 ± 3.241%) in comparison to marketed formulation (42.81 ± 1.452%) after 48 h. In vivo histopathological studies in rats for 14 days of application of prepared nanogel showed improvement in the wound healing potential as compared to marketed formulation.

Topical Delivery of Fenoprofen Calcium via Elastic Nano-vesicular Spanlastics: Optimization Using Experimental Design and In Vivo Evaluation.

The aim of this study was to investigate the potential of surfactant-based nanovesicular system (spanlastics) for topical delivery of fenoprofen calcium (FPCa) to eliminate its oral gastrointestinal adverse effects. FPCa-loaded spanlastics were prepared by thin film hydration (TFH) technique according to a full factorial design to investigate the influence of formulation variables on the drug entrapment efficiency (%EE), particle size (PS), deformability index (DI), and the % drug released after 24 h through the cellulose membrane (Q24h) using Design-Expert® software. The optimized formula (composed of Span 60 and Tween 60 as an edge activator at weight ratio of 8: 2 in presence of Transcutol P as a cosolvent in the hydration media) exhibited the highest %EE (49.91 ± 2.60%), PS of 536.1 ± 17.14 nm, DI of 5.07 ± 0.06 g, and Q24h of 61.11 ± 2.70%; it was also characterized for morphology and physical stability. In vitro release study of FPCa-loaded spanlastic gel and conventional FPCa gel through a synthetic membrane and hairless rat skin were evaluated. The skin permeation study revealed that spanlastic gel exhibited both consistent and prolonged action. Finally, the % inhibition of carrageenan-induced rat paw edema of spanlastic gel was three times higher than the conventional FPCa gel after 24 h. In conclusion, spanlastic-based gel could be a great approach for improving topical delivery of fenoprofen calcium, providing both prolonged and enhanced anti-inflammatory activity in the treatment of arthritis.

Formulation Optimization and Ex Vivo and In Vivo Evaluation of Celecoxib Microemulsion-Based Gel for Transdermal Delivery.

Celecoxib (CXB) is a poorly aqueous solubility sulfonamide non-steroidal anti-inflammatory drug (NSAID). Hence, the formulation of CXB was selected for solubilization and bioavailability. To find out suitable formulation for microemulsion, the solubility of CXB in triacetin (oil phase), Tween 80 (surfactant), and Transcutol-P (co-surfactant) was screened respectively and optimized by using orthogonal experimental design. The Km value and concentration of oil, Smix, and water were confirmed by pseudo-ternary phase diagram studies and central composite design. One percent carbopol 934 was added to form CXB microemulsion-based gel. The final formulation was evaluated for its appearance, pH, viscosity, stability, drug content determination, globule size, and zeta potential. Its ex vivo drug permeation and the in vivo pharmacokinetic was investigated. Further research was performed to ensure the safety and validity by skin irritation study and in vivo anti-inflammatory activity study. Ex vivo permeation study in mice was designed to compare permeation and transdermal ability between microemulsion formulation and conventional gel. The results revealed that optimized microemulsion-based gel gained higher permeation based on smaller globule size and high drug loading of microemulsion. Transdermal ability was also greatly improved. Bioavailability was compared to market Celebrex® by the in vivo pharmacokinetic study in rabbits. The results indicated that CXB microemulsion-based gel had better bioavailability than Celebrex®.

Vesicles from pH-regulated reversible gemini amino-acid surfactants as nanocapsules for delivery.

Reversible transition from micelles to vesicles by regulating pH were realized by gemini amino-acid surfactants N,N'-dialkyl-N,N'-diacetate ethylenediamine. Measurement results of ζ-potential at different pH and DLS at varying solvents revealed that the protonation between H(+) and double NCH2COO(-) groups (generating NH(+)CH2COO(-)), expressed as pKa1 and pKa2, is the key driving force to control the aggregation behaviors of gemini surfactant molecule. Effect of pH on the bilayer structure was studied in detail by using steady-state fluorescence spectroscopy of hydrophobic pyrene and Coumarin 153 (C153) respectively and fluorescence resonance energy transfer (FRET) from C153 to Rhodamine 6G (R6G). Various pH-regulated and pH-reversible self-assemblies were obtained in one surfactant system. Vitamin D3 was encapsulated in vesicle bilayers to form nano-VD3-capsules as VD3 supplement agent for health care products. By using the electrostatic attraction between Ca(2+) and double -COO(-) groups, nano-VD3-capsules with Ca(2+) coated outermost layers were prepared as a formulation for VD3 and calcium co-supplement agent. DLS and TEM were performed to check stability and morphology of the nano-capsules. It is concluded that the pH-regulated gemini amino-acid surfactants can be used to construct colloidal systems for delivering hydrophobic drugs or nutritions without lipids at human physiological pH level.

Influence of surfactants in self-microemulsifying formulations on enhancing oral bioavailability of oxyresveratrol: Studies in Caco-2 cells and in vivo.

Self-microemulsifying drug delivery systems (SMEDDS) containing two types (Tween80 and Labrasol) and two levels (low; 5% and high; 15%) of co-surfactants were formulated to evaluate the impact of surfactant phase on physical properties and oral absorption of oxyresveratrol (OXY). All formulations showed a very rapid release in the simulated gastric fluid (SGF) pH 1.2. After dilution with different media, the microemulsion droplet sizes of the Tween80-based (∼26 to 36 nm) were smaller than that of the Labrasol-based systems (∼34 to 45 nm). Both systems with high levels of surfactant increased the Caco-2 cells permeability of OXY compared to those with low levels of surfactant (1.4-1.7 folds) and the unformulated OXY (1.9-2.0 folds). It was of interest, that there was a reduction (4.4-5.3 folds) in the efflux transport of OXY from both systems compared to the unformulated OXY. The results were in good agreement with the in vivo absorption studies of such OXY-formulations in rats. Significantly greater values of Cmax and AUC(0-10h) (p<0.05) were obtained from the high levels of Tween80-based (F(r,0-10h) 786.32%) compared to those from the Labrasol-based system (F(r,0-10h) 218.32%). These finding indicate the importance of formulation variables such as type and quantity of surfactant in the SMEDDS to enhance oral drug bioavailability.

The Design of Amphiphilic Polymeric Micelles of Curcumin for Cancer Management.

Curcumin, a natural phenolic compound mainly extracted from turmeric curcuma longa, has been employed to prevent or treat plenty of diseases particularly cancer. It has been proven to modulate various signal transduction pathways and exhibits antiinflammatory, anti-oxidative, anti-metastasis anti-proliferative, anti-angiogenic in addition anti-cancer activities. However, its poor solubility and rapid degradation severely hampers the introduction into clinical setting. In this review, we focus on the design of polymeric micelles (PMMCs) which are nano-scaled drug delivery vehicles and fabricated from biocompatible polymers for efficient curcumin delivery. In particular, recent progress of curcumin loaded internal stimuli responsive PMMCs for further intracellular uptake via internal triggers is also discussed.

Preoperative bowel preparation in children: polyethylene glycol versus normal saline.

BACKGROUND: Colorectal surgeries frequently require bowel preparation. In children, (is this standard of care?: this method is mostly followed) this is usually performed using normal saline, which is very cumbersome and causes unnecessary discomfort. This study compared polyethylene glycol (PEG) with normal saline for preoperative bowel preparation in children. PATIENTS AND METHODS: Thirty patients, admitted in the Department of Paediatric Surgery, Rajindra Hospital, Patiala, for colonic and colorectal surgical procedures, were divided into two groups, I (PEG) and II (NS), randomly for bowel preparation with PEG and normal saline, respectively. RESULTS: It was found that there was no significant difference in the quality of preparation (P > 0.05), but PEG use was found to be easier, more comfortable and acceptable for the patients, their relatives and the hospital staff. Overall, complications are significantly lesser for PEG preparation (P < 0.05). There was no significant difference in the overall cost. CONCLUSION: Thus, it can be inferred that PEG may be a safe, cost-effective and acceptable option for large bowel preparation.