209 research outputs found
Mind “De GaPP”: in vitro efficacy of deferiprone and gallium-protoporphyrin against Staphylococcus aureus biofilms
No full textData source: Supporting information, http://onlinelibrary.wiley.com/doi/10.1002/alr.21735/abstract#footer-support-infoAbstract not availableKatharina Richter, Mahnaz Ramezanpour, Nicky Thomas, Clive A. Prestidge, Peter-John Wormald and Sarah Vreugd
Silica-lipid hybrid (SLH) microcapsules: a novel oral delivery system for poorly soluble drugs
No full textAbstract not availableAngel Tan, Spomenka Simovic, Andrew K. Davey, Thomas Rades, Clive A. Prestidg
Temperature-induced gelation of emulsions stabilised by responsive copolymers: A rheological study
No full textThe steady-state and dynamic rheological properties of 1-bromohexadecane-in-water emulsions stabilised by responsive poly(N-isopropylacrylamide)-co-poly(ethyleneglycol methacrylate) (poly(NIPAM-co-PEGMa)) copolymer have been investigated. The data were compared to measurements performed using dilute and concentrated poly(NIPAM-co-PEGMa) copolymer solutions. These solutions exhibit viscosities that decrease and increase, respectively, with increasing temperature. The increase in viscosity for the concentrated solution is attributed to transient network formation. The presence of dispersed oil droplets (volume fraction = 0.30) in the emulsion causes temperature-induced gelation even though the copolymer concentration in the aqueous phase is such that transient network formation due to overlapping copolymer chains throughout the aqueous phase does not occur. Dynamic rheological data confirmed gelation for the emulsions at elevated temperatures. Emulsion gelation is attributed to flocculation between neighbouring droplets. The adhesive droplets form a network that entraps the aqueous phase. The strength of the network increased with increasing temperature. To our knowledge these data represent the first comprehensive rheological investigation of reversible, temperature-induced gelation for an oil-in-water emulsion.Andrew Y. C. Koh, Clive Prestidge, Igor Ametov and Brian R. Saunder
A topical hydrogel with deferiprone and gallium-protoporphyrin targets bacterial iron metabolism and has antibiofilm activity
No full textAccepted manuscript posted online 10 April 2017Many infectious diseases are associated with multidrug-resistant (MDR) bacteria residing in biofilms that require high antibiotic concentrations. While oral drug delivery is frequently ineffective, topical treatments have the potential to deliver higher drug concentrations to the infection site while reducing systemic side effects. This study determined the antibiofilm activity of a surgical wound gel loaded with the iron chelator deferiprone (Def) and the heme analogue gallium-protoporphyrin (GaPP), alone and in combination with ciprofloxacin. Activity against MDR Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter johnsonii biofilms was assessed in the colony biofilm and artificial wound model by enumeration of CFU and correlative light/electron microscopy. While Staphylococcus biofilms were equally susceptible to GaPP and Def-GaPP gels (log10 reduction of 3.8 and 3.7, respectively), the Def-GaPP combination was crucial for significant activity against P. aeruginosa biofilms (log10 reduction of 1.3 for GaPP and 3.3 for Def-GaPP). When Def-GaPP gel was combined with ciprofloxacin, the efficacy exceeded the activity of the individual compounds. Def-GaPP delivered in a surgical wound gel showed significant antibiofilm activity against different MDR strains and could enhance the gel's wound-healing properties. Moreover, Def-GaPP indicated a potentiation of ciprofloxacin. This antibiofilm strategy has potential for clinical utilization as a therapy for topical biofilm-related infections.Katharina Richter, Nicky Thomas, Jolien Claeys, Jonathan McGuane, Clive A. Prestidge, Tom Coenye, Peter-John Wormald, Sarah Vreugd
A Liposome-Micelle-Hybrid (LMH) Oral Delivery System for Poorly Water-Soluble Drugs: Enhancing Solubilisation and Intestinal Transport
No full textA novel liposome-micelle-hybrid (LMH) carrier system was developed as a superior oral drug delivery platform compared to conventional liposome or micelle formulations. The optimal LMH system was engineered by encapsulating TPGS micelles in the aqueous core of liposomes and its efficacy for oral delivery was demonstrated using lovastatin (LOV) as a model poorly soluble drug with P-gp (permeability glycoprotein) limited intestinal absorption. LOV-LMH was characterised as unilamellar, spherical vesicles encapsulating micellar structures within the interior aqueous core and showing an average diameter below 200 nm. LMH demonstrated enhanced drug loading, water apparent solubility and extended/controlled release of LOV compared to conventional liposomes and micelles. LMH exhibited enhanced LOV absorption and transportation in a Caco-2 cell monolayer model of the intestine by inhibiting the P-gp transporter system compared to free LOV. The LMH system is a promising novel oral delivery approach for enhancing bioavailability of poorly water-soluble drugs, especially those presenting P-gp effluxes limited absorption
Capturing and Quantifying Particle Transcytosis with Microphysiological Intestine-on-Chip Models
No full textData source: Supporting information, https://doi.org/10.1002/smtd.202200989Understanding the intestinal transport of particles is critical in several fields ranging from optimizing drug delivery systems to capturing health risks from the increased presence of nano- and micro-sized particles in human environment. While Caco-2 cell monolayers grown on permeable supports are the traditional in vitro model used to probe intestinal absorption of dis-solved molecules, they fail to recapitulate the transcytotic activity of polar-ized enterocytes. Here, an intestine-on-chip model is combined with in silico modeling to demonstrate that the rate of particle transcytosis is ≈350× higher across Caco-2 cell monolayers exposed to fluid shear stress compared to Caco-2 cells in standard “static” configuration. This relates to profound phe-notypical alterations and highly polarized state of cells grown under mechan-ical stimulation and it is shown that transcytosis in the microphysiological model is energy-dependent and involves both clathrin and macropinocytosis mediated endocytic pathways. Finally, it is demonstrated that the increased rate of transcytosis through cells exposed to flow is explained by a higher rate of internal particle transport (i.e., vesicular cellular trafficking and baso-lateral exocytosis), rather than a change in apical uptake (i.e., binding and endocytosis). Taken together, the findings have important implications for addressing research questions concerning intestinal transport of engineered and environmental particles.Ludivine C. Delon, Matthew Faria, Zhengyang Jia, Stuart Johnston, Rachel Gibson, Clive A. Prestidge, and Benjamin Thierr
Liposome-Micelle-Hybrid (LMH) Carriers for Controlled Co-Delivery of 5-FU and Paclitaxel as Chemotherapeutics
No full textPaclitaxel (PTX) and 5-fluorouracil (5-FU) are clinically relevant chemotherapeutics, but both suffer a range of biopharmaceutical challenges (e.g., either low solubility or permeability and limited controlled release from nanocarriers), which reduces their effectiveness in new medicines. Anticancer drugs have several major limitations, which include non-specificity, wide biological distribution, a short half-life, and systemic toxicity. Here, we investigate the potential of liposome-micelle-hybrid (LMH) carriers (i.e., drug-loaded micelles encapsulated within drug-loaded liposomes) to enhance the co-formulation and delivery of PTX and 5-FU, facilitating new delivery opportunities with enhanced chemotherapeutic performance. We focus on the combination of liposomes and micelles for co-delivery of PTX and 5_FU to investigate increased drug loading, improved solubility, and transport/permeability to enhance chemotherapeutic potential. Furthermore, combination chemotherapy (i.e., containing two or more drugs in a single formulation) may offer improved pharmacological performance. Compared with individual liposome and micelle formulations, the optimized PTX-5FU-LMH carriers demonstrated increased drug loading and solubility, temperature-sensitive release, enhanced permeability in a Caco-2 cell monolayer model, and cancer cell eradication. LMH has significant potential for cancer drug delivery and as a next-generation chemotherapeutic
Distribution and Inhibition of liposomes on Staphylococcus aureus and Pseudomonas aeruginosa biofilm
No full textBACKGROUND Staphylococcus aureus and Pseudomonas aeruginosa are major pathogens in chronic rhinosinusitis (CRS) and their biofilms have been associated with poorer postsurgical outcomes. This study investigated the distribution and anti-biofilm effect of cationic (+) and anionic (-) phospholipid liposomes with different sizes (unilamellar and multilamellar vesicle, ULV and MLV respectively) on S. aureus and P. aeruginosa biofilms. METHOD Specific biofilm models for S. aureus ATCC 25923 and P. aeruginosa ATCC 15692 were established. Liposomal distribution was determined by observing SYTO9 stained biofilm exposed to DiI labeled liposomes using confocal scanning laser microscopy, followed by quantitative image analysis. The anti-biofilm efficacy study was carried out by using the alamarBlue assay to test the relative viability of biofilm treated with various liposomes for 24 hours and five minutes. RESULTS The smaller ULVs penetrated better than larger MLVs in both S. aureus and P. aeruginosa biofilm. Except that +ULV and –ULV displayed similar distribution in S. aureus biofilm, the cationic liposomes adhered better than their anionic counterparts. Biofilm growth was inhibited at 24-hour and five-minute exposure time, although the decrease of viability for P. aeruginosa biofilm after liposomal treatment did not reach statistical significance. CONCLUSION The distribution and anti-biofilm effects of cationic and anionic liposomes of different sizes differed in S. aureus and P. aeruginosa biofilms. Reducing the liposome size and formulating liposomes as positively charged enhanced the penetration and inhibition of S. aureus and P. aeruginosa biofilms.Dong Dong, Nicky Thomas, Benjamin Thierry, Sarah Vreugde, Clive A. Prestidge, Peter-John Wormal
Plasma functionalized PDMS microfluidic chips: towards point-of-care capture of circulating tumor cells
No full textThe main challenge in the isolation of circulating tumor cells (CTCs) resides in their extreme rarity in blood. Here we report on the design of efficient and disposable microfluidic CTC capture devices based on the plasma functionalization of PDMS and its subsequent conjugation with the anti-epithelial-cell adhesion-molecule (EpCAM) mAb. Model studies on planar surfaces demonstrated excellent immuno-specificity of cancer-cell capture using NCI H69 small-cell lung cancer cells and SK-Br-3 breast cancer cells. Taking advantage of the transparency of the PDMS device, direct observation of the capture events on the internal 3D microstructure of the device could be achieved. At a flow rate of 16 μL min−1, an overall capture efficiency of 80 to 90% is determined in cell-spiking experiments in PBS. In accordance with direct microscopic observations, an increased flow rate (48 μL min−1) only has a minor effect (30% reduction) on cell-capture efficiency. Capture efficiency of the device using cancer cells spiked in whole blood is above 70%. The combination of soft lithography and plasma-based functionalization described in this work enables the facile fabrication of efficient and disposable CTC capture devices based on PDMS, which could facilitate the transition of this new technology into the clinical environment.Mahaveer D. Kurkuri, Fares Al-Ejeh, Jun Yan Shi, Dennis Palms, Clive Prestidge, Hans J. Griesser, Michael P. Brown and Benjamin Thierr
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