Development of mucoadhesive sprayable gellan gum fluid gels

The nasal mucosa provides a potentially good route for local and systemic drug delivery. However, the protective feature of the nasal cavity make intranasal delivery challenging. The application of mucoadhesive polymers in nasal drug delivery systems enhances the retention of the dosage form in the nasal cavity. Several groups have investigated using low acyl gellan as a drug delivery vehicle but only limited research however, has been performed on high acyl gellan for this purpose, despite its properties being more conducive to mucoadhesion. High acyl gellan produces highly elastic gels below 60 °C which make it difficult to spray using a mechanical spray device. Therefore, in this study we have tried to address this problem by making fluid gels by introducing a shear force during gelation of the gellan polymer. These fluid gel systems contain gelled micro-particles suspended in a solution of un-gelled polymer. These systems can therefore behave as pourable viscoelastic fluids. In this study we have investigated the rheological behavior and mucoadhesion of fluid gels of two different types of gellan (high and low acyl) and fluid gels prepared from blends of high and low acyl gellan at a 50:50 ratio. The results demonstrated that by preparing fluid gels of high acyl gellan, the rheological properties were sufficient to spray through a standard nasal spray device. Moreover fluid gels also significantly enhance both high acyl and low acyl gellan mucoadhesion properties

Evaluation of gellan gum fluid gels as modified release oral liquids

Oral liquids are often preferred for drug administration to patients for whom swallowing is difficult, however formulating modified release versions can be challenging. A potential route to achieve modified release in oral liquids is by using fluid (sheared) gels formed by introducing a shear field during gelation in gel-forming biopolymers. These fluid gels can act as pourable viscoelastic fluids but retain true gel micro/nano structure. Here, we have demonstrated that fluid gels have potential as paediatric oral liquids preventing release of ibuprofen in simulated gastric fluid. Subsequent release at pH 7.4 was affected by the duration of exposure and magnitude of acid pH with a linear relationship between onset of release and the preceding acidic exposure duration. Delayed release was a result of increasing gel stiffness, a consequence of the acidity of the initial release media and exposure time. A much faster release rate was measured when exposure time in acid was 10 min compared with 60 min. This study highlights the potential to design fluid gels that are tuned to have a specified stiffness at a particular pH and exposure time. This could enable the preparation oral liquids with modified release behaviour

Robust spatially resolved pressure measurements using MRI with novel buoyant advection-free preparations of stable microbubbles in polysaccharide gels

MRI of fluids containing lipid coated microbubbles has been shown to be an effective tool for measuring the local fluid pressure. However, the intrinsically buoyant nature of these microbubbles precludes lengthy measurements due to their vertical migration under gravity and pressure-induced coalescence. A novel preparation is presented which is shown to minimize both these effects for at least 25 min. By using a 2% polysaccharide gel base with a small concentration of glycerol and 1,2-distearoyl-sn-glycero-3-phosphocholine coated gas microbubbles, MR measurements are made for pressures between 0.95 and 1.44 bar. The signal drifts due to migration and amalgamation are shown to be minimized for such an experiment whilst yielding very high NMR sensitivities up to 38% signal change per bar

Design of hybrid gels based on gellan-cholesterol derivative and P90G liposomes for drug depot applications

Gels are extensively studied in the drug delivery field because of their potential benefits in therapeutics. Depot gel systems fall in this area, and the interest in their development has been focused on long-lasting, biocompatible, and resorbable delivery devices. The present work describes a new class of hybrid gels that stem from the interaction between liposomes based on P90G phospholipid and the cholesterol derivative of the polysaccharide gellan. The mechanical properties of these gels and the delivery profiles of the anti-inflammatory model drug diclofenac embedded in such systems confirmed the suitability of these hybrid gels as a good candidate for drug depot applications

Adsorption of carboxylic modified latex particles at liquid interfaces studied by the gel trapping technique

We have studied how carboxylic modified latex (CML) microparticles adsorb at liquid surfaces and the preferred type of emulsion they can stabilise depending on the particle size and the surface density of carboxylic groups. We measured the particle contact angle by using the gel trapping technique (GTT) for CML particles adsorbed at air–water and oil–water interfaces. Using this method we obtained scanning electron microscopy (SEM) micrographs of polydimethylsiloxane (PDMS) replicas of the liquid interface with the particles, where the PDMS replicates the non-polar phase and measured the particle contact angle. We discovered that the particle wettability correlates well with the surface density of the carboxylic groups but is not very sensitive to the presence of electrolyte in the aqueous phase and the value of the particle zeta potential. We demonstrated that CML microparticles with a high surface density of COOH groups stabilise oil-in-water (O/W) emulsions while those with the lowest coverage of COOH groups favour the formation of water-in-oil (W/O) emulsions. We found that this corresponds to a change of the CML particle contact angle from lower than 90° to higher than 90° upon decrease of the surface density of COOH groups. The findings confirm that the surface density of polar groups has a much bigger effect on the particle wettability and the preferred emulsion than the particle surface charge and zeta potential. Our results on the type of stabilised Pickering emulsion agree with other experimental studies with different particle materials. We propose an alternative explanation for the link between the particle contact angle and the type of stabilised Pickering emulsion

The parallel lives of polysaccharides in food and pharmaceutical formulations

The present opinion article discusses how polysaccharide structures can be used in both food and pharmaceutical formulations. We distinguish two regions depending on moisture content where polysaccharides form structures with distinct functional properties. Some trends in key areas of active research are assessed and in particular edible films, encapsulation, polycrystalline polysaccharides, protein-polysaccharide coacervation and fluid gels. We unveil that the physicochemical principles that are shared across the food and pharmaceutical disciplines provide a great opportunity for cross-disciplinary collaboration. We finally argue that such co-operation will help tackling polysaccharide functionality issues that are encountered in both areas

Wear Tests of a Potential Biolubricant for Orthopedic Biopolymers

Most wear testing of orthopedic implant materials is undertaken with dilute bovine serum used as the lubricant. However, dilute bovine serum is different to the synovial fluid in which natural and artificial joints must operate. As part of a search for a lubricant which more closely resembles synovial fluid, a lubricant based on a mixture of sodium alginate and gellan gum, and which aimed to match the rheology of synovial fluid, was produced. It was employed in a wear test of ultra high molecular weight polyethylene pins rubbing against a metallic counterface. The test rig applied multidirectional motion to the test pins and had previously been shown to reproduce clinically relevant wear factors for ultra high molecular weight polyethylene. After 2.4 million cycles (125 km) of sliding in the presence of the new lubricant, a mean wear factor of 0.099 × 10−6 mm3/Nm was measured for the ultra high molecular weight polyethylene pins. This was over an order of magnitude less than when bovine serum was used as a lubricant. In addition, there was evidence of a transfer film on the test plates. Such transfer films are not seen clinically. The search for a lubricant more closely matching synovial fluid continues

An ultra melt-resistant hydrogel from food grade carbohydrates

© 2017 The Royal Society of Chemistry. We report a binary hydrogel system made from two food grade biopolymers, agar and methylcellulose (agar-MC), which does not require addition of salt for gelation to occur and has very unusual rheological and thermal properties. It is found that the storage modulus of the agar-MC hydrogel far exceeds those of hydrogels from the individual components. In addition, the agar-MC hydrogel has enhanced mechanical properties over the temperature range 25-85 °C and a maximum storage modulus at 55 °C when the concentration of methylcellulose was 0.75% w/v or higher. This is explained by a sol-gel phase transition of the methylcellulose upon heating as supported by differential scanning calorimetry (DSC) measurements. Above the melting point of agar, the storage modulus of agar-MC hydrogel decreases but is still an elastic hydrogel with mechanical properties dominated by the MC gelation. By varying the mixing ratio of the two polymers, agar and MC, it was possible to engineer a food grade hydrogel of controlled mechanical properties and thermal response. SEM imaging of flash-frozen and freeze-dried samples revealed that the agar-MC hydrogel contains two different types of heterogeneous regions of distinct microstructures. The latter was also tested for its stability towards heat treatment which showed that upon heating to temperatures above 120 °C its structure was retained without melting. The produced highly thermally stable hydrogel shows melt resistance which may find application in high temperature food processing and materials templating

Co-axial wet-spinning in 3D Bioprinting: state of the art and future perspective of microfluidic integration

Nowadays, 3D bioprinting technologies are rapidly emerging in the field of tissue engineering and regenerative medicine as effective tools enabling the fabrication of advanced tissue constructs that can recapitulate in vitro organ/tissue functions. Selecting the best strategy for bioink deposition is often challenging and time consuming process, as bioink properties-in the first instance, rheological and gelation-strongly influence the suitable paradigms for its deposition. In this short review, we critically discuss one of the available approaches used for bioprinting-namely co-axial wet-spinning extrusion. Such a deposition system, in fact, demonstrated to be promising in terms of printing resolution, shape fidelity and versatility when compared to other methods. An overview of the performances of co-axial technology in the deposition of cellularized hydrogel fibres is discussed, highlighting its main features. Furthermore, we show how this approach allows (i) to decouple the printing accuracy from bioink rheological behaviour-thus notably simplifying the development of new bioinks- A nd (ii) to build heterogeneous multi-materials and/or multicellular constructs that can better mimic the native tissues when combined with microfluidic systems. Finally, the ongoing challenges and the future perspectives for the ultimate fabrication of functional constructs for advanced research studies are highlighted. © 2018 IOP Publishing Ltd