Physical characterisation and component release of poly(vinyl alcohol)-tetrahydroxyborate hydrogels and their applicability as potential topical drug delivery systems

Poly(vinyl alcohol)-tetrahydroxyborate (PVA-THB) hydrogels are dilatant formulations with potential for topical wound management. To support this contention, the physical properties, rheological behaviour and component release of candidate formulations were investigated. Oscillatory rheometry and texture profile analysis were used at room temperature and 37 °C. Results showed that it was possible to control the rheological and textural properties by altering component concentration and modifying the type of PVA polymer used. Hydrogels made using PVA grades with higher degrees of hydrolysis displayed favourable characteristics from a wound healing perspective. In vitro release of borate and PVA were assessed in order to evaluate potential clinical dosing of free species originating from the hydrogel structure. Component diffusion was influenced by both concentration and molecular weight, where relevant, with up to 5% free PVA cumulative release observed after 30 min. The results of this study demonstrated the importance of poly(vinyl alcohol) selection for ensuring appropriate gel formation in PVA-THB hydrogels. The benefits of higher degrees of hydrolysis, in particular, included lower excipient release and reduced bioadhesion. The unique physical characteristics of these hydrogels make them an appealing delivery vehicle for chronic and acute wound management purposes.

Preliminary clinical assessment of polyvinyl alcohol-tetrahydroxyborate hydrogels as potential topical formulations for local anesthesia of lacerations

The aim of this study was to assess a novel semisolid material as a potential topical drug delivery system for acute laceration. The objectives were to correlate physical characterization data using rheologic studies and to compare with clinical assessment of performance in an emergency department (ED).

Quantification of singlet oxygen generation from photodynamic hydrogels

Recently, we described a series of novel porphyrin-impregnated hydrogels capable of producing microbicidal singlet oxygen (1O2) on photoactivation. Indirect assessment of the efficacy of 1O2 production from such hydrogels has been previously described using microbiological techniques, but here we report a novel, direct method of quantification. Anthracene-9,10-dipropionic acid (ADPA) is known to irreversibly form an endoperoxide on reaction with 1O2, causing photobleaching of its absorbance band at approximately 378 nm. Here, the reaction of this probe is exploited in a novel way to provide a simple, inexpensive, and convenient measurement of 1O2 generation from the surface of porphyrin-incorporated photosensitising hydrogels, with the ability to account for effects due to hydrogel porosity. Ingress of the probe into the materials was observed, with rates of up to 3.83 x 103 s-1. This varied by up to 200-fold with material composition and surface modification. Rates of 1O2 generation in these porphyrin-incorporated hydrogels, after compensating for ADPA ingress, ranged from 1.86x103 – 5.86x103 s-1. This work demonstrates a simple and straightforward method for direct 1O2 quantification from porous materials, with general utility.

Thermosensitive hydrogels of poly(methyl vinyl ether-co-maleic anhydride) - Pluronic (R) F127 copolymers for controlled protein release

Thermosensitive hydrogels are of a great interest due to their many biomedical and pharmaceutical applications. In this study, we synthesized a new series of random poly (methyl vinyl ether-co-maleic anhydride) (Gantrez (R) AN, GZ) and Pluronic (R) F127 (PF127) copolymers (GZ-PF127), that formed thermosensitive hydrogels whose gelation temperature and mechanical properties could be controlled by the molar ratio of GZ and PF127 polymers and the copolymer concentration in water. Gelation temperatures tended to decrease when the GZm/PF127 ratio increased. Thus, at a fixed GZm/PF127 value, sol-gel temperatures decreased at higher copolymer concentrations. Moreover, these hydrogels controlled the release of proteins such as bovine serum albumin (BSA) and recombinant recombinant kinetoplastid membrane protein of Leishmania (rKMP-11) more than the PF127 system. Toxicity studies carried out in J774.2 macrophages showed that cell viability was higher than 80%. Finally, histopathological analysis revealed that subcutaneous administration of low volumes of these hydrogels elicited a tolerable inflammatory response that could be useful to induce immune responses against the protein cargo in the development of vaccine adjuvants.

Non-covalent hydrogels of cyclodextrins and poloxamines for the controlled release of proteins

Different types of gels were prepared by combining poloxamines (Tetronic), i.e. poly(ethylene oxide)/poly(propylene oxide) (PEO/PPO) octablock star copolymers, and cyclodextrins (CD). Two different poloxamines with the same molecular weight (ca. 7000) but different molecular architectures were used. For each of their four diblock arms, direct Tetronic 904 presents PEO outer blocks while in reverse Tetronic 90R4 the hydrophilic PEO blocks are the inner ones. These gels were prepared by combining alpha-CD and poloxamine aqueous solutions. The physicochemical properties of these systems depend on several factors such as the structure of the block copolymers and the Tetronic/alpha-CD ratio. These gels were characterized using differential scanning calorimetry (DSC), viscometry and X-ray diffraction measurements. The 90R4 gels present a consistency that makes them suitable for sustained drug delivery. The resulting gels were easily eroded: these complexes were dismantled when placed in a large amount of water, so controlled release of entrapped large molecules such as proteins (Bovine Serum Albumin, BSA) is feasible and can be tuned by varying the copolymer/CD ratio. 

Release of β-galactosidase from poloxamine/α-cyclodextrin hydrogels

All mammals lose their ability to produce lactase (β-galactosidase), the enzyme that cleaves lactose into galactose and glucose, after weaning. The prevalence of lactase deficiency (LD) spans from 2 to 15% among northern Europeans, to nearly 100% among Asians. Following lactose consumption, people with LD often experience gastrointestinal symptoms such as abdominal pain, bowel distension, cramps and flatulence, or even systemic problems such as headache, loss of concentration and muscle pain. These symptoms vary depending on the amount of lactose ingested, type of food and degree of intolerance. Although those affected can avoid the uptake of dairy products, in doing so, they lose a readily available source of calcium and protein. In this work, gels obtained by complexation of Tetronic 90R4 with α-cyclodextrin loaded with β-galactosidase are proposed as a way to administer the enzyme immediately before or with the lactose-containing meal. Both molecules are biocompatible, can form gels in situ, and show sustained erosion kinetics in aqueous media. The complex was characterized by FTIR that evidenced an inclusion complex between the polyethylene oxide block and α-cyclodextrin. The release profiles of β-galactosidase from two different matrices (gels and tablets) of the in situ hydrogels have been obtained. The influence of the percentage of Tetronic in media of different pH was evaluated. No differences were observed regarding the release rate from the gel matrices at pH 6 (t50 = 105 min). However, in the case of the tablets, the kinetics were faster and they released a greater amount of 90R4 (25%, t50 = 40–50 min). Also, the amount of enzyme released was higher for mixtures with 25% Tetronic. Using suitable mathematical models, the corresponding kinetic parameters have been calculated. In all cases, the release data fit quite well to the Peppas–Sahlin model equation, indicating that the release of β-galactosidase is governed by a combination of diffusion and erosion processes. It has been observed that the diffusion mechanism prevails over erosion during the first 50 minutes, followed by continued release of the enzyme due to the disintegration of the matrix.

Bioactive Gyroid Scaffolds Formed by Sacrificial Templating of Nanocellulose and Nanochitin Hydrogels as Instructive Platforms for Biomimetic Tissue Engineering

A sacrificial templating process using lithographically printed minimal surface structures allows complex de novo geometries of delicate hydrogel materials. The hydrogel scaffolds based on cellulose and chitin nanofibrils show differences in terms of attachment of human mesenchymal stem cells, and allow their differentiation into osteogenic outcomes. The approach here serves as a first example toward designer hydrogel scaffolds viable for biomimetic tissue engineering.

Fulfilling the 3Rs: Galleria mellonella as an In Vivo Model to Assess the Antimicrobial Efficacy of Self-assembling Peptide Hydrogels

The concept of ‘The Three Rs’ (The 3Rs: reduction, refinement and replacement) is an important consideration in the development of alternatives to animal testing in medical research. Invertebrate models such as Galleria mellonella are advantageous both economically and ethically.1 Galleria have proven to be effective alternatives to assess the antimicrobial activity of novel therapeutics.2
In this study Galleria mellonella are validated and used as an in vivo infection model to determine the antimicrobial activity of a novel self-assembling antimicrobial peptide NapFFKK.3 The peptide was considered as being non-toxic to the Galleria with 100% survival 120 hours post inoculation with NapFFKK. Following inoculation with Pseudomonas aeruginosa PAO1, Escherichia coli ATCC 11303, Staphylococcus epidermidis ATCC 35984 and Staphylococcus aureus ATCC 6538, the highest concentration allowing survival was selected and used as the test inoculum. Haemolymph was extracted from inoculated and peptide treated Galleria at either 24 or 72 hours post-treatment. Reduction in bacterial load was determined in comparison to a positive control. Bacterial load was decreased in all treated Galleria with decreasing antimicrobial activity demonstrated with a decreased concentration of peptide (2- log cycle reduction achieved in Escherichia coli inoculated Galleria treated with 2% NapFFKK). The results are promising regarding the use of Galleria mellonella as an infection model and NapFFKK as an effective novel antimicrobial.