Abstract
AUS-CRS 2011, the 5th Annual Meeting of the Australian Chapter of the Controlled Release Society was held as a satellite meeting to the Australian Peptide Conference at Hamilton Island, Queensland, Australia in October 2011. The conference provides a forum for showcasing a range of research towards improving drug delivery across Australia and New Zealand, with international visitors from beyond also participating, this year from the UK and Sweden. This year‘s meeting had an emphasis on peptide and protein delivery because of its association with the Australian Peptide Conference, although invited and contributed talks from a range of other fields of delivery research were also presented with excellent talks on lipid-based drug delivery, pulmonary delivery, anticancer drug delivery and drug development from a range of academic and industry speakers.
Peptide & protein delivery
With dark skies and heavy rain outside, AUS-CRS 2011 was the place to be at Hamilton Island, a tropical island off the coast of northern Queensland. With formalities out of the way, the scientific program for the conference was underway, with the Plenary Speaker, Martin Malmsten from the University of Uppsala, Sweden giving his presentation titled ‘Peptides and proteins in polyelectrolyte microgels,‘ which highlighted the issues associated with charge association of peptides and proteins with hydrogels, the influence of microgel structure, and consequent potential for shell formation as opposed to uniform particle loading.
There were three papers presented in the interaction of peptides and proteins with solid inorganic materials and consequent release behavior. Michael (Chengzhong) Yu from University of Queensland (Australia) described his research using temperature-controlled vacuum-assisted vapour deposition to control the pore size in mesoporous materials. Application in both enrichment and detection of peptides in serum, and to the controlled loading and release of camptothecin were demonstrated. Continuing the theme of inorganic drug-delivery matrices, Ramin Rohanizadeh (University of Sydney, Australia) discussed the differential adsorption of proteins onto crystalline hydroxyapatite and amorphous calcium phosphate, and rationalized differences in protein release rate from the materials. A novel approach to reveal subtle changes in protein conformation at the surface of porous silicon using time-of-flight–secondary ion MS was described by Tim Barnes (University of South Australia). Differences in the complex amino-acid fragmentation patterns provided discrimination between native and denatured human serum albumin, insulin and papain as model compounds Citation[1].
To complete the protein- and peptide-delivery session, there were two presenters from New Zealand. The preparation of injectable implants using β-glucan was the topic presented by Ilva Rupenthal (University of Auckland, New Zeland). Rheological behavior was correlated with drug release profiles and the optimal matrix was found to comprise aβ-glucan and polyethylene glycol (PEG) mixture. Thomas Rades (University of Otago, New Zealand) gave an account of the preparation, release and efficacy of a GnRH analog from polyalkylcyanoacrylate nanoparticles. The potential for copolymerization of the peptide with poly(alkyl cyanoacrylate) during particle preparation was highlighted as a possible limitation in translation to human treatments, but the particles were shown to provide effective oral sterilization of brushtail possums, a devastating agricultural pest in New Zealand, the main target of the delivery system.
Lipid-based drug delivery
The lipid-based drug-delivery session had a focus on self-assembled lipid systems that form micelles and exotic mesophase structures such as bicontinuous cubic phases and cubosomes. Martina Stenzel (Centre for Advanced Macromolecular Design, The University of New South Wales, Sydney, Australia) presented her exciting work on designing RAFT polymers to form block co-polymer micelles where drug is either solubilized into the micelle via hydrophobic interactions Citation[2], or grafted covalently to the polymer. Impressive delivery results for platinum drugs were exemplified and attributed to enhanced stability of the micellar structures through design with very low critical micelle concentrations, but which disassemble upon cellular uptake. Three highly complementary talks followed, which expounded the virtues of self-assembled cubic phases as drug-delivery and bioimaging systems.
Patrick Hartley (Commonwealth Scientific and Industrial Research Organization [CSIRO], Clayton, Australia) presented recent studies investigating the influence of fusogenic lipids on the biological interactions of cubic-phase particles, cubosomes, with biological surfaces. Using primarily surface-sensitive techniques, it was shown that introduction of phosphatidyl serine residues into phytantriol-based cubosomes not only increases their cellular association and uptake, but also their cytotoxicity Citation[3]. The results have implications for the use of these particles as drug-delivery systems for siRNA and other therapeutics. Xavier Mulet (Monash Institute of Pharmaceutical Sciences and CSIRO) described his recent efforts towards constructing multifunctional cubosomes that possess targeting capability towards specific tissues. Addressing the colloidal stability and stealth capability of the particles is an important first stage for this work, and he presented recent work aimed at discovering novel stabilisers using high throughput technologies. The incorporation of quantum dots into the particles to impart an imaging functionality and future plans to control drug release through investigations of alternative novel self-assembled structures were highlighted.
The final speaker of the session was Ben Boyd (Monash Institute of Pharmaceutical Sciences, Parkville, Australia) who illustrated his group‘s efforts towards the development of light-activated drug-release systems, taking advantage of the thermodynamic stability and reversibility of self-assembled systems to design systems for ‘on-demand‘ release. Reversible control over drug release due to changes in light responsiveness have been demonstrated by his group. In this presentation, he focused on the use of photothermal and photochromic approaches to achieve remote activation of drug release for more convenient and effective treatment of macular degeneration.
An emerging formulation approach for poorly water-soluble drugs, ‘silica–lipid hybrid‘ capsules, similar to Pickering emulsions, was presented by Clive Prestidge (University of South Australia). The silica enables preparation of a dry powder that contains a high proportion of lipid enabling the benefits of both lipid formulations and solid dose forms manufacture. The particles modify the rate of lipolysis, drug release and inhibit drug precipitation, leading to improved bioavailability Citation[4].
Pulmonary delivery
Late speaker cancellations meant that only two presentations could be provided on pulmonary drug delivery. With increasing interest on controlling local availability of drug in the lung after pulmonary administration Citation[5], a fantastic perspective on the appropriateness of pharmacopoeial methods for studying drug dissolution to predict in vivo dissolution and release behavior of drug particles in the lung was provided by Daniela Traini (Faculty of Pharmacy, University of Sydney, Australia). Dissolution studies with sodium cromoglycate showed that the standard USP2 dissolution apparatus is a poor predictor of likely in vivo dissolution profiles, failing to discriminate between different formulations. However, Franz diffusion cells, essentially being a ‘wetted-surface model‘ are more representative of the in vivo lung surface and provided much greater discrimination between the performance of formulations.
David Cipolla from Aradigm Corp. (USA) followed with discussion of an atypical formulation behavior in vivo. A formulation expected to provide rapid dissolution and absorption of drug due to deep-lung penetration actually provided slower uptake than a formulation that demonstrated less effective deep-lung delivery. Reasons for the difference were speculated upon and discussion around preferential sites of drug absorption from lung ensued.
Anticancer drug delivery
A number of presentations centred on the discovery and delivery of anticancer compounds. Mary Bebawy (UTS, Pharmacy, University of Technology Sydney, Australia) has discovered a novel ‘non-genetic‘ pathway of multi-drug resistance acquisition by cancer cells, in which microparticles provide the vehicle for intercellular transfer of functional P-glycoprotein from resistant (MDR+) donor cells to drug sensitive (MDR-)recipient cells Citation[6].
Two new types of anticancer candidates were described at the meeting. Targeting anticancer drugs based on α-tocopherol succinate using a triphenylphosphine lipophilic cationic group provided a highly effective compound inhibiting mitochondrial aspiration and showing efficacy against human breast cancer xenografts Citation[7] (Steve Ralph, Griffith University, Queensland, Australia), Jackie Wilce (Monash University, Clayton, Australia) has been investigating a cell-permeable non-phosphorylated cyclic peptide (G7–18NATE) that specifically inhibits the SH2 domain in Grb7b protein, which plays a role in tyrosine kinase signaling, leading to inhibiting cancer cell proliferation and migration Citation[8].
In addition, two novel approaches in the delivery of anticancer compounds were also described. Lee-Yong Lim (University of Western Australia) described the interactions between wheat germ agglutinin, functionalized PLGA nanoparticles, loaded with paclitaxel. Greater cytotoxicity against LS174T mucin-secreting colon cancer cells was attributable to slow diffusion and retention in the mucous layer prolonging particle residence time in the vicinity of the cells compared with controls. YanYan from Frank Caruso‘s group at University of Melbourne, Australia, described the intracellular release of doxorubicin from layer-by-layer capsules, which correlated to cytotoxicity of paclitaxel loaded capsules against LIM 1899 human colorectal cancer cells. Binding of the capsules to cell surfaces was a key step facilitated by exofacialthiols on the cell membrane.
Drug development & delivery
Michael Kassiou (University of Sydney, Australia) presented a fascinating account of his research on using in vivo PET imaging in primates to detect overexpression of translocator protein an indicator of microglial activation leading to neurodegenerative diseases Citation[9]. The administration of neuroprotective agents was shown to mitigate microgliosis and the technique provides a new path to discovery of neuroprotective compounds that target translocator protein. The CNS delivery theme was continued by Pavla Simerska (University of Queensland, Australia), an expert in lipopolysaccharide synthesis for facilitating the delivery of vaccines. The lipid moiety increases the partition of compounds across biological barriers, while the polysaccharide units provide the targeting function and solubility. Her presentation described a new library of compounds designed for delivery and targeting of enkpentapeptide, a pain regulator, which binds to opioid receptors in the CNS.
Novel drug–polymer conjugates under development by PolyActiva (Australia) for the treatment of ocular diseases were described by Andrew Donohue. Release of ciprofloxacin for post-surgical prophylaxis against infection was at therapeutic levels (>MIC in the vitreous chamber) for over 120 days. A glaucoma treatment is also under development using the same technology.
Student poster prizes were awarded to Stephanie Phan from the Monash Institute of Pharmaceutical Sciences (‘Investigating the evolution of nanostructure during digestion of lipid-based drug-delivery systems‘) and Warren Truong from the University of New South Wales (‘The Release of Therapeutics from Self-Assembling Hydrogels‘) to support travel to the 2012 CRS Annual Meeting in Quebec City, Canada.
Summary
In summary, this highly informative and efficient 2-day meeting was a great success, with a number of collaborations arising from discussions and networking, as well as great exposure for the students involved. The quality of the meeting was, again, testament to the growing significance of drug-delivery research across Australia. Plans for the next meeting in Melbourne in December 2012 are already underway.
Financial & competing interests disclosure
BJ Boyd is currently President of the Australian Chapter of the Controlled Release Society. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.
No writing assistance was utilized in the production of this manuscript.
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