In Vitro Release from Reverse Poloxamine/alpha-Cyclodextrin Matrices: Modelling and Comparison of Dissolution Profiles

Gels obtained by complexation of octablock star polyethylene oxide/polypropylene oxide copolymers (Tetronic 90R4) with -cyclodextrin (-CD) were evaluated as matrices for drug release. Both molecules are biocompatible so they can be potentially applied to drug delivery systems. Two different types of matrices of Tetronic 90R4 and -CD were evaluated: gels and tablets. These gels are capable to gelifying in situ and show sustained erosion kinetics in aqueous media. Tablets were prepared by freeze-drying and comprising the gels. Using these two different matrices, the release of two model molecules, L-tryptophan (Trp), and a protein, bovine serum albumin (BSA), was evaluated. The release profiles of these molecules from gels and tablets prove that they are suitable for sustained delivery. Mathematical models were applied to the release curves from tablets to elucidate the drug delivery mechanism. Good correlations were found for the fittings of the release curves to different equations. The results point that the release of Trp from different tablets is always governed by Fickian diffusion, whereas the release of BSA is governed by a combination of diffusion and tablet erosion. 

Punctal plug: a medical device to treat dry eye syndrome and for sustained drug delivery to the eye

Punctal plugs (PPs) are miniature medical implants that were initially developed for the treatment of dry eyes. Since their introduction in 1975, many PPs made from different materials and designs have been developed. PPs, albeit generally successful, suffer from drawbacks such as epiphora and suppurative canaliculitis. To overcome these issues intelligent designs of PPs were proposed (e.g. SmartPLUG™ and Form Fit™). PPs are also gaining interest among pharmaceutical scientists for sustaining drug delivery to the eye. This review aims to provide an overview of PPs for dry eye treatment and drug delivery to treat a range of ocular diseases. It also discusses current challenges in using PPs for ocular diseases.

Microwave-Assisted Preparation of Hydrogel-Forming Microneedle Arrays for Transdermal Drug Delivery Applications

A microwave (MW)-assisted crosslinking process to prepare hydrogel-forming microneedle (MN) arrays was evaluated. Conventionally, such MN arrays are prepared using processes that includes a thermal crosslinking step. Polymeric MN arrays were prepared using poly(methyl vinyl ether-alt-maleic acid) crosslinked by reaction with poly(ethylene glycol) over 24 h at 80 °C. Polymeric MN arrays were prepared to compare conventional process with the novel MW-assisted crosslinking method. Infrared spectroscopy was used to evaluate the crosslinking degree, evaluating the area of the carbonyl peaks (2000–1500 cm−1). It was shown that, by using the MW-assisted process, MN with a similar crosslinking degree to those prepared conventionally can be obtained in only 45 min. The effects of the crosslinking process on the properties of these materials were also evaluated. For this purpose swelling kinetics, mechanical characterisation, and insertion studies were performed. The results suggest that MN arrays prepared using the MW assisted process had equivalent properties to those prepared conventionally but can be produced 30 times faster. Finally, an in vitro caffeine permeation across excised porcine skin was performed using conventional and MW-prepared MN arrays. The release profiles obtained can be considered equivalent, delivering in both cases 3000–3500 μg of caffeine after 24 h.

Patient safety and beyond: what should we expect from microneedle arrays in the transdermal delivery arena?

Research based upon microneedle (MN) arrays has intensified recently. While the initial focus was on biomolecules, the field has expanded to include delivery of conventional small-molecule drugs whose water solubility currently precludes transdermal administration. Much success has been achieved, with peptides, proteins, vaccines, antibodies and even particulates delivered by MN in therapeutic/prophylactic doses. Recent innovations have focused on enhanced formulation design, scalable manufacture and extension of exploitation to minimally invasive patient monitoring, ocular delivery and enhanced administration of cosmeceuticals. Only two MN-based drug/vaccine delivery products are currently marketed, partially due to limitations with older MN designs based upon silicon and metal. Even the more promising polymeric MN have raised a number of regulatory and manufacturability queries that the field must address. MN arrays have tremendous potential to yield real benefits for patients and industry and, through diligence, innovation and collaboration, this will begin to be realised over the next 3-5 years.

Development of polymeric–cationic peptide composite nanoparticles, a nanoparticle-in-nanoparticle system for controlled gene delivery

We report the formulation of novel composite nanoparticles that combine the high transfection efficiency of cationic peptide-DNA nanoparticles with the biocompatibility and prolonged delivery of polylactic acid–polyethylene glycol (PLA-PEG). The cationic cell-penetrating peptide RALA was used to condense DNA into nanoparticles that were encapsulated within a range of PLA-PEG copolymers. The composite nanoparticles produced exhibited excellent physicochemical properties including size <200 nm and encapsulation efficiency >80%. Images of the composite nanoparticles obtained with a new transmission electron microscopy staining method revealed the peptide-DNA nanoparticles within the PLA-PEG matrix. Varying the copolymers modulated the DNA release rate >6 weeks in vitro. The best formulation was selected and was able to transfect cells while maintaining viability. The effect of transferrin-appended composite nanoparticles was also studied. Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.

Multifunctional Delivery Systems for Cancer Gene Therapy

This chapter examines key concepts with respect to cancer gene therapy and the current issues with respect to non-viral delivery. The biological and molecular barriers that need to be overcome before effective non-viral delivery systems can be appropriately designed for oncology applications are highlighted and ways to overcome these are discussed. Strategies developed to evade the immune response are also described and targeted gene delivery is examined with the most effective strategies highlighted. Finally, this chapter proposes a new way forward based on a growing body of evidence that supports a multifunctional delivery approach involving the creation of vectors, with a unique molecular architecture designed using a bottom-up approach.

Injurious tail biting in pigs: How can it be controlled in existing systems without tail docking?

Tail biting is a serious animal welfare and economic problem in pig production. Tail docking, which reduces but does not eliminate tail biting, remains widespread. However, in the EU tail docking may not be used routinely, and some 'alternative' forms of pig production and certain countries do not allow tail docking at all. Against this background, using a novel approach focusing on research where tail injuries were quantified, we review the measures that can be used to control tail biting in pigs without tail docking. Using this strict criterion, there was good evidence that manipulable substrates and feeder space affect damaging tail biting. Only epidemiological evidence was available for effects of temperature and season, and the effect of stocking density was unclear. Studies suggest that group size has little effect, and the effects of nutrition, disease and breed require further investigation. The review identifies a number of knowledge gaps and promising avenues for future research into prevention and mitigation. We illustrate the diversity of hypotheses concerning how different proposed risk factors might increase tail biting through their effect on each other or on the proposed underlying processes of tail biting. A quantitative comparison of the efficacy of different methods of provision of manipulable materials, and a review of current practices in countries and assurance schemes where tail docking is banned, both suggest that daily provision of small quantities of destructible, manipulable natural materials can be of considerable benefit. Further comparative research is needed into materials, such as ropes, which are compatible with slatted floors. Also, materials which double as fuel for anaerobic digesters could be utilised. As well as optimising housing and management to reduce risk, it is important to detect and treat tail biting as soon as it occurs. Early warning signs before the first bloody tails appear, such as pigs holding their tails tucked under, could in future be automatically detected using precision livestock farming methods enabling earlier reaction and prevention of tail damage. However, there is a lack of scientific studies on how best to respond to outbreaks: the effectiveness of, for example, removing biters and/or bitten pigs, increasing enrichment, or applying substances to tails should be investigated. Finally, some breeding companies are exploring options for reducing the genetic propensity to tail bite. If these various approaches to reduce tail biting are implemented we propose that the need for tail docking will be reduced. © 2014 The Animal Consortium.