Target-specific delivery of doxorubicin to retinoblastoma using epithelial cell adhesion molecule aptamer

PURPOSE: To study target-specific delivery of doxorubicin (Dox) using an RNA aptamer against epithelial cell adhesion molecule (EpCAM) in retinoblastoma (RB) cells. METHODS: The binding affinity of the EpCAM aptamer to RB primary tumor cells, Y79 and WERI-Rb1 cells, and Müller glial cell lines were evaluated with flow cytometry. Formation of physical conjugates of aptamer and Dox was monitored with spectrofluorimetry. Cellular uptake of aptamer-Dox conjugates was monitored through fluorescent microscopy. Drug efficacy was monitored with cell proliferation assay. RESULTS: The EpCAM aptamer (EpDT3) but not the scrambled aptamer (Scr-EpDT3) bound to RB tumor cells, the Y79 and WERI-Rb1 cells. However, the EpCAM aptamer and the scrambled aptamer did not bind to the noncancerous Müller glial cells. The chimeric EpCAM aptamer Dox conjugate (EpDT3-Dox) and the scrambled aptamer Dox conjugate (Scr-EpDT3-Dox) were synthesized and tested on the Y79, WERI-Rb1, and Müller glial cells. The targeted uptake of the EpDT3-Dox aptamer caused cytotoxicity in the Y79 and WERI-Rb1 cells but not in the Müller glial cells. There was no significant binding or consequent cytotoxicity by the Scr-EpDT3-Dox in either cell line. The EpCAM aptamer alone did not cause cytotoxicity in either cell line. CONCLUSIONS: The results show that the EpCAM aptamer-Dox conjugate can selectively deliver the drug to the RB cells there by inhibiting cellular proliferation and not to the noncancerous Müller glial cells. As EpCAM is a cancer stem cell marker, this aptamer-based targeted drug delivery will prevent the undesired effects of non-specific drug activity and will kill cancer stem cells precisely in RB.

Differences in primary health care delivery to Australia's Indigenous population : a template for use in economic evaluations

Background Health economics is increasingly used to inform resource allocation decision-making, however, there is comparatively little evidence relevant to minority groups. In part, this is due to lack of cost and effectiveness data specific to these groups upon which economic evaluations can be based. Consequently, resource allocation decisions often rely on mainstream evidence which may not be representative, resulting in inequitable funding decisions. This paper describes a method to overcome this deficiency for Australia’s Indigenous population. A template has been developed which can adapt mainstream health intervention data to the Indigenous setting.

Methods The ‘Indigenous Health Service Delivery Template’ has been constructed using mixed methods, which include literature review, stakeholder discussions and key informant interviews. The template quantifies the differences in intervention delivery between best practice primary health care for the Indigenous population via Aboriginal Community Controlled Health Services (ACCHSs), and mainstream general practitioner (GP) practices. Differences in costs and outcomes have been identified, measured and valued. This template can then be used to adapt mainstream health intervention data to allow its economic evaluation as if delivered from an ACCHS.

Results The template indicates that more resources are required in the delivery of health interventions via ACCHSs, due to their comprehensive nature. As a result, the costs of such interventions are greater, however this is accompanied by greater benefits due to improved health service access. In the example case of the polypill intervention, 58% more costs were involved in delivery via ACCHSs, with 50% more benefits. Cost-effectiveness ratios were also altered accordingly.

Conclusions The Indigenous Health Service Delivery Template reveals significant differences in the way health interventions are delivered from ACCHSs compared to mainstream GP practices. It is important that these differences are included in the conduct of economic evaluations to ensure results are relevant to Indigenous Australians. Similar techniques would be generalisable to other disadvantaged minority populations. This will allow resource allocation decision-makers access to economic evidence that more accurately represents the needs and context of disadvantaged groups, which is particularly important if addressing health inequities is a stated goal.

Integrated microfluidic drug delivery devices : a component view

Research on drug delivery devices is progressing rapidly with the main objective being the delivery of precise quantity of drugs into the target area of the body. A drug delivery device (DDD) needs to accurately control the flow rate of drug delivery and protects the body from undesired additional doses. An integrated microfluidic drug delivery device (IMDDD) is a miniature device that can regulate and monitor the delivery of the right amount of drug using micro-scale components. IMDDDs offer several advantages including ease of use, electro-chemical controllability, low power consumption, simplicity, fast fabrication, and good bio-compatibility. Various IMDDDs have been developed for treatment of cancer, cardiovascular disorder, eye and brain diseases, stress, and diabetes. This paper presents a generic architecture for IMDDDs, discusses the existing drug delivery methods, summarizes the specifications of the components, and identifies a number of performance evaluation parameters. The operation of IMDDDs is presented through fourteen potential internal components. In addition, recommendations on how enhance the design and fabrication process of IMDDDs are given.

Novel alginate-enclosed chitosan–calcium phosphate-loaded iron-saturated bovine lactoferrin nanocarriers for oral delivery in colon cancer therapy

Aim: To develop polymeric-ceramic nanocarriers (NCs) in order to achieve oral delivery of the anticancer neutraceutical iron-saturated bovine lactoferrin (Fe-bLf) protein.

Materials & methods: Fe-bLf or paclitaxel (Taxol®) were adsorbed onto calcium phosphate nanocores, enclosed in biodegradable polymers chitosan and alginate. The Fe-bLf or Taxol-loaded NCs indicated as AEC–CP–Fe-bLf or AEC–CP–Taxol NCs, respectively, were made by combination of ionic gelation and nanoprecipitation. Size distribution, morphology, internalization and release profiles of the NCs were studied along with evaluation of in vitro and in vivo anticancer activities and compared with paclitaxel.

Results: AEC–CP–Fe-bLf NCs obtained spherical morphology and showed enhanced endocytosis, transcytosis and anticancer activity in Caco-2 cells in vitro. AEC–CP–Fe-bLf NCs were supplemented in an AIN 93G diet and fed to mice in both prevention and treatment human xenograft colon cancer models. AEC–CP–Fe-bLf NCs were found to be highly significantly effective when given orally, as a pretreatment, 1 week before Caco-2 cell injections. None of the mice from the AEC–CP–Fe-bLf NC-fed group developed tumors or showed any signs of toxicity, while the mice fed the control AIN 93G diet showed normal tumor growth. Fe-bLf or Taxol, when given orally in a diet as nanoformulations post-tumor development, showed a significant regression in the tumor size with complete inhibition of tumor growth later, while intratumoral injection of Taxol just delayed the growth of tumors. The pharmacokinetic and bioavailability studies indicated that nanoformulated Fe-bLf was predominantly present on tumor cells compared to non-nanoformulated Fe-bLf. Fe-bLf-loaded NCs were found to help in absorption of iron and thus may have utility in enhancing the iron uptake during iron deficiency without interfering with the absorption of calcium.

Conclusion: With the promising results of our study, the future potential of NC-loaded Fe-bLf in chemoprevention and in the treatment of human colon cancer, deserves further investigation for translational research and preclinical studies of other malignancies.

Nano-lactoferrin in diagnostic, imaging and targeted delivery for cancer and infectious diseases

Lactoferrin (Lf) is a natural occurring iron binding protein present in many mammalian excretions and involved in various physiological processes. Lf is used in the transport of iron along with other molecules and ions from the digestive system. However its the modulatory functions exhibited by Lf in connection to immune response, disease regression and diagnosis that has made this protein an attractive therapeutic against chronic diseases. Further, the exciting potentials of employing nanotechnology in advancing drug delivery systems, active disease targeting and prognosis have also shown some encouraging outcomes. This review focuses on the role of Lf in diagnosing infection, cancer, neurological and inflammatory diseases and the recent nanotechnology based strategies.

Integrated construction supply chain design and delivery solutions

This study describes the development of a decision framework to support multi-disciplinary information and knowledge management model which focuses on integrated design and delivery solutions for all construction supply chain actors. The framework was developed within the context of two national information technology research projects in Australia. The first study used diffusion theory to explain the barriers and enablers to future adoption of advanced information technology solutions such as building information modelling (BIM). A grounded theory methodology was deployed and a pathways model for innovative information technology diffusion accommodating diverse patterns of adoption and different levels of expertize was developed. The second study built on the findings of the first study but specifically focussed on innovators, early and late adopters of BIM and the development of a decision framework towards advanced collaborative platform solutions. This study summarizes the empirical results of the previous studies. The core of the decision framework is the creation, use and ownership of building information sub-models and integrated models. The decision framework relies on holistic collaborative design management. Design expertise is diffused and can be found in various locations along the construction supply chain within project teams. A wide definition of design is considered from conceptual to developed to detailed design. The recent development to the decision model offers much potential as the early upstream decisions are often made in a creative, collaborative and uncertain environment. However, decision making needs to balance both a reductionist and exploratory creative empowerment approach. Shared team expertise and competency and team mental models are explored as a fundamental requirement to collaborative BIM. New skills in interdisciplinarity are discussed as an implication of future construction industry collaborative platforms.

Nanostructured liquid crystalline particles as an alternative delivery vehicle for plant agrochemicals

Agrochemical spray formulations applied to plants are often mixed with surfactants that facilitate delivery of the active ingredient. However, surfactants cause phytotoxicity and off-target effects in the environment. We propose the use of nanostructured liquid crystalline particles (NLCP) as an alternative to surfactant-based agrochemical delivery. For this, we have compared the application of commercial surfactants, di (2-ethylhexyl) sulfosuccinate and alkyl dimethyl betaine, with NLCP made from phytantriol, at concentrations of 0.1%, 1% and 5% on the adaxial surface of leaves of four plant species Ttriticum aestivum (wheat), Zea mays (maize), Lupinus angustifolius (lupin), and Arabidopsis thaliana. In comparison with the application of surfactants there was less phytotoxicity on leaves of each species following treatment with NLCP. Following treatment of leaves with NLCP analysis of cuticular wax micromorphology revealed less wax solubilization in the monocot species. The results clearly show that there are advantages in the use of NLCP rather than surfactants for agrochemical delivery.

Chitosan-modified PLGA nanoparticles with versatile surface for improved drug delivery

Shortage of functional groups on surface of poly(lactide-co-glycolide) (PLGA)-based drug delivery carriers always hampers its wide applications such as passive targeting and conjugation with targeting molecules. In this research, PLGA nanoparticles were modified with chitosan through physical adsorption and chemical binding methods. The surface charges were regulated by altering pH value in chitosan solutions. After the introduction of chitosan, zeta potential of the PLGA nanoparticle surface changed from negative charge to positive one, making the drug carriers more affinity to cancer cells. Functional groups were compared between PLGA nanoparticles and chitosan-modified PLGA nanoparticles. Amine groups were exhibited on PLGA nanoparticle surface after the chitosan modification as confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The modified nanoparticles showed an initial burst release followed by a moderate and sustained release profile. Higher percentage of drugs from cumulative release can be achieved in the same prolonged time range. Therefore, PLGA nanoparticles modified by chitosan showed versatility of surface and a possible improvement in the efficacy of current PLGA-based drug delivery system.