Reflections on guest lectures performed by Dr. Furong Tian overviewing the relevance of nanotechnology for drug delivery and Dr. Christine O’Connor overviewing Metal Drugs for multi-model applications

Dr. Furong Tian has a Bachelor’s degree in medicine, a master’s in Biochemistry and a PhD in Chemifurongstry currently working as the assistant lecturer in Dublin Institute of Technology while continuing research in the field of Nanotechnology for different disease treatments and diagnostics where Dr. Tian has received funding under a Marie Curie Intra European fellowship and the European Network Program ERANET Nanoscience to continue her research in nanotechnology.

Dr Christine O’Connor is currently a lecturer in Chemical and Pharmaceuticchrisal sciences in Dublin Institute of Technology who completed her PhD in Dublin City University in 1999 under Professor Han Vos. Dr. O’Connor’s research is focused on metal based drugs for multi-model applications, which she has published and co-published many papers within the area of modern pharmaceuticals and drug delivery.


Dr. Furong Tian – “The study and application of Nanotechnology based drugs and diagnostic techniques”

Dr. Tian began her guest lecture explaining and introducing the basics of nanotechnology. Tian compared the size of a strand of hair, to a bacteria cell, to a virus, with an aim of creating an image in her listener’s head of how small the scale for sizing different objects and cells is. Tian explained that 1mm is equal to 1000µm, whereas 1µm is equal to 1000nm. Most drugs are produced with a dosage in µg, which shows how much less dosage nanotechnology based drugs deliver in comparison, where Tian also stated that only 0.5% of a drug reaches its desired target. The scale at which nanotechnology is performed is so small, that drugs produced using nanoparticles are mainly focused and implemented to pass through hard to access areas of the body to reach areas such as the brain and central nervous system which are protected by the blood brain barrier.


Figure 1 – Different applications for Nanomedicine and functionalized nanoparticles [1]

Tian discussed topics such as the use of nanoparticles in IVIS imaging and Vevo imaging systems as non-invasive strategies for mapping the spread of disease in the body, and locating tumours within animal models using bioluminescence and ultrasound techniques. Tian discussed her own research in these areas, discussing factors such as the length of time research must be conducted for before reaching in-vivo model research and displayed promising results from her own experimental data showing that these strategies were effective at identifying tumours in rats during in-vivo studies. Tian discussed areas of her own in-vivo research where she has performed analysis of radio labelled NP’s through inhalation, intra-tracheal and intra-venous application.

Dr. Christine O’Connor – The use of metal-based drugs for multi-model applications in drug delivery

Dr. O’Connor structured her talk about the use of metal-based drugs for multi-model applications, and simplified the topic down for her audience by describing the mechanism of these drugs as “using a metal to pretend it is iron in a biological system”. The metal based drugs are compound specific, and have molecules manipulated for specific reasons based on logical assumptions using inorganic chemistry. O’Connor discussed her own research and the use of rare earth metals, maximising expensive Ruthenium Complexes which have promising electronic and structural properties for compounds within metal based drugs.


Figure 2 – The Elemental Properties and electron valency of Ruthenium [2]

O’Connor discussed the different PIP signalling pathways that a drug can travel through, BPIP < NPIP < FPIP < CPIP with regards to electron affinity. Metal based drugs research has come to a standstill in recent years, with the last published research coming in 2001 and 2005 in this area, which O’Connor believes that there is potential for the synthesis of new metal based compounds for analysis and for new research to be performed on adding to the existing knowledge in this area.

Another topic that was discussed was bioassay testing, in which O’Connor stated that when new compounds are synthesised, testing these compounds on healthy cell lines determining cytotoxicity is also essential because it is also important to see what effects these compounds have on the healthy cell lines as well as the cancerous cell lines. When a compound has a low cytotoxicity in healthy cell lines, there are less side effects caused during chemotherapy treatments.

The final topic discussed was the susceptibility rate of the Irish population to cancer, with 1/10 people developing breast cancer and 1/2 people developing some form of cancer in general. O’Connor discussed the ability of targeting cancerous cells folate receptors using cyclodextrin to enhance the delivery of drugs to the target cancerous cells through increasing the binding affinity of drugs.

Conclusion and Relevance

This discussion about the importance of nanotechnology for the development of new drug delivery strategies and systems is essential to progression within the drug delivery field, because the use of these nanomaterials to deliver compounds to areas of the body that could not be reached previously, opens the door for new drugs to be developed, which is why this topic is so relevant to the learning module. Tian’s research relates to the learning content in this module since some drugs that have already been developed, that are known to work and create a therapeutic response for the treatment of specific diseases, but are not able to reach their targeted destination due to barriers of delivery that degrade the drug within the body. Through the use of nanotechnology, these drugs can be altered to change the way the drug is administered and delivered which can improve efficacy.

Current research ongoing for nanomedicines are focused on the delivery of specific therapeutic compounds using nanomaterials called “Nano Vehicles” such as Liposomes, Polymeric micelles, Dendrimers, etc. These Nano-Vehicles are currently hot topics in nanotechnology research due to the non-toxic, biocompatible, non-immunogenic and biodegradable properties that they hold for drug delivery systems. Nanomedicines are also focusing on imaging techniques similar to Tian’s research, such as passive and active targeting through nanoparticles, where the mechanism of action can be seen in Figure 3 where Qdot-antibody probes were used to map out the area of tumors within the body.

Passive active tumour targetting

Figure 3 – An example of Passive and Active tumor targetting mechanisms using Qdot-antibody probes to identify tumour antigens during in-vivo studies [1]

Nanotechnology studies for drug delivery are being further developed in the area by using DNA as a “Smart Material” for the construction of nanovehicles. The applications of DNA based nanostructures are still in their infancy, and possess many obstacles for implementation and delivery, but possess great potential for facilitating and passing biological barriers in targeted drug delivery [3].

For an example of research into the use of nanotechnology for the delivery of compounds that have a proven therapeutic response, but cannot reach their target destination with a strong efficacy due to the barriers of distribution, is a study performed using biodegradable core multishell nanocarriers to carry the anti-inflammatory drug “Dexamethasone” resulting a better transport capacity for the drug when administered using the nanocarrier. Two variations of the multishell nanocarriers were analysed and exhibited good stability, low cytotoxicity, and opportunity for production upscale [4].

In regard to metal based drugs with current ongoing research, Graphene based nanocarriers are being developed in research being conducted for novel based drug carriers to aid drug delivery of anti-cancer drugs, drugs with poor solubility, antibiotics, antibodies, peptides and genes; specifically the application of Graphene and Graphene Oxide (GO) based drugs [5].


[1] – Y. liu, H. Miyoshi (June 2007). Nanomedicine for drug delivery and imaging: A promising avenue for cancer therapy and diagnosis using targeted functional nanoparticles. International Journal of Cancer. n/a (120), 2527-2537.

[2] – LiveScience Staff. (29/05/2013). Facts about Ruthenium. Available: Last accessed 20/04/2017.

[3] – Anders H. Okholm. (2016). DNA nanovehicles and the biological barriers. Advanced Drug Delivery Reviews. 106 (Abstract), 183-191.

[4] – Fang Du. (2016). Development of biodegradable hyperbranched core-multishell nanocarriers for efficient topical drug delivery. Journal of Controlled Release. 242 (Abstract), 42-49.

[5] – Qi Zhang. (2017). Advanced review of graphene-based nanomaterials in drug delivery systems: Synthesis, modification, toxicity and application. Materials Science and Engineering C. n/a (6. Drug Delivery Applications of Graphene), n/a.




“The Delivery of therapeutics through the Blood Brain Barrier” – A critical review of the paper “Nanomedicine as a non-invasive strategy for drug delivery across the blood brain barrier” by Vivienne H.Tam, Chris Sosa and Rui Lui for the International Journal of pharmaceuticals.


Vivienne H. Tam. (2016). Nanomedicine as a non-invasive strategy for drug delivery across the blood brain barrier. International Journal of Pharmaceutics. 515 (n/a), 331-342.

Figure 1

Figure 1 – The cerebral capillary of the BBB and an example of the obstacles presented by the structure [1]

The paper that has been chosen to be critically reviewed was published in 2016 by Vivienne H. Tam, Chris Sosa, and Rui Lui for the International Journal of Pharmaceuticals targeting individuals within the field of drug delivery. The title of this paper is “Nanomedicine as a non-invasive strategy for drug delivery across the blood brain barrier” and researches invasive and non-invasive strategies for treating the Central Nervous System (CNS) through the Blood Brain Barrier (BBB). The paper is well researched with 70+ references, focusing heavily on nanomedicine as a non-invasive strategy, and the strengths and weaknesses of the types of nanocarriers, types of targeting mechanisms and methods of applications for these nanomedicine therapies [1].

Background to the BBB [6]

The paper states that the BBB serves a natural protective function to prevent entry of toxic substances into the CNS [1,2], which has shown to be the most tightly regulated and biologically complex structure to penetrate within the drug delivery field [1,3]. The focus of this paper is on the lack of available treatments for neurological diseases, such as Alzheimer’s and Parkinson’s, and how nanomedicines can penetrate the BBB and access the CNS to treat such diseases. Current nanoparticles characteristics that are essential to the implementation within food and medicine products are displayed in Figure 2, with nanomaterials present in food products being monitored and regulated by OSHA and the EPA, while nanomaterials used in nanomedicines are monitored and regulated by the FDA [7]. These organisations are essential for the collaboration between industry and manufacturing agencies to ensure the production of safe and effective nanomedicines and therapies in the future. Currently there is a wide range of materials being employed in the synthesis of nanocarriers, which can be grouped into inorganic, polymer and lipid-based materials [8] used in the production of invasive and non-invasive nanomedicines.



Figure 2 – Comparative characteristics of nanomaterials used in medicine and foods regulated by the OSHA, EPA and FDA [7]

The BBB can transport essential nutrients, for the normal metabolism of the brain cells, while providing protection against harmful toxic compounds and bacteria [4]. The BBB is a major obstacle in the field of drug delivery due to its complex structure of endothelial cells, surrounding its microvasculature network of blood vessels, which make it nearly impermeable to drug therapies. The article displays an excellent figure displaying the structure and components of the BBB that can be seen in “figure 1”. Tam states that the main obstacle for the development of therapies related to the brain is the mechanism of transportation of the drugs through and into the BBB matrix which is backed up by numerous papers in the field [1,2,3,5]. Tight junctions in between the endothelial cells prevent the passage of larger molecules, by limiting diffusion of polar molecules, from the blood, through the capillaries, with the additional defence of P-Glycoprotein efflux pumps expelling any foreign substances that gain access to the BBB [1,2]. Compounds that are lipophilic have shown that they can diffuse across the BBB, but endogenous membrane transport proteins, as mentioned before, expel the molecules back into the bloodstream before they can perform their pharmacodynamic functions. The largest molecule able to pass through the BBB is >500 Da, which eliminates nearly 100% of drugs and therapeutics for the treatment of the CNS due to the inability of the compounds to diffuse across the BBB [2]. The development of specific targeting ligands, endogenous proteins, or antibodies against specific receptors (TFRC; INSR) that can cause receptor mediated transcytosis, and can pass the biological therapeutics through the BBB, are some of the new innovative ideas implemented within drug delivery research [3]. [Reference new therapies here]


Figure 2

Figure 3 – Transport routes across the BBB [1]

Invasive and Non-invasive strategies for Drug Delivery

There are two main strategies for the treatment of the CNS through the BBB that this paper focused on, which are invasive and non-invasive strategies. Invasive methods involve the disruption of the structure of the BBB’s endothelial cells which can temporarily increase permeability and pass macromolecular drugs directly through the BBB, with methods such as injections into the CNS tissue to cause a therapeutic effect, and disruptive techniques; such as Osmotic Shock to shrink the endothelial cells and allow sufficient drug molecules to pass the BBB, and Ultrasound mediated drug delivery (USMD) that uses 1-10µm microbubbles to disrupt the tight junctions and allow for enhanced chemotherapy treatments. Invasive strategies can be accompanied by high neurosurgical costs and increased risk of infections, when the BBB has been exposed, for undesirable elements to enter [1], so, as invasive strategies are more effective on the removal or treatment of well-defined tumours, they are less desirable in the treatment of less localized diseases such as Alzheimer’s and Parkinson’s disease or multiple sclerosis [1,2]. From November 1999 to May 2005, a clinical trial was conducted on the treatment of cerebral metastases in 38 volunteers using invasive methods, which are the most common intracranial brain tumours among adults, using palliative radio therapy by D. Fortin, in which the trial evaluated the effectiveness of the treatment in enhancement of the survival rate associated with multiple cerebral metastases conditions. The results of the trial determined the mean survival rates of patients with various carcinomas, with ”promising results occurring for multiple brain metastasis of ovarian carcinoma, adeno- carcinoma of lung, small cell lung carcinoma, and systemic lymphoma” [9].

The paper points out that the adverse consequences of using invasive therapies have led to the development of new non-invasive therapies that can penetrate the BBB without exposing the brain to harmful infections or bacteria. Intranasal mechanisms were designed to permit transport to the brain through non-invasive perineural or perivascular channels through olfactory nerves, but poor absorption across the nasal epithelium has limited the delivery efficacy. The use of Mannitol as a chemical disruption mechanism has also been implemented to cause osmotic-driven movement of fluid out of the cells causing them to shrink leading to fenestration of cerebral cells [5].

Figure 3Figure 4 – Nanoparticles and their biophysicochemical characteristics [1]

The main topic of this paper is nanomedicines, which is discussed in detail to give the reader insights on the delivery of macromolecules to the CNS through the BBB using nanocarriers such as Liposomes, Polymeric nanoparticles, Solid-Lipid Nanoparticles (NPLs), and Magnetic nanoparticles (MNPs). The paper also discusses the targeting mechanisms involved in delivering drugs past the BBB with mechanisms such as Carrier Mediated Transport (CMT), Receptor Mediated Transport (RMT), and Absorptive-Mediated Transport (AMT) [1]. Tam states that the use of nanoparticles in the development of therapeutics and diagnostics, that are functionalized with multiple ligands and probes, gives the ability to produce specific properties in nanomedicines that researchers desire called “Theranostic agents”. In an in-vivo study performed on rats by G.R Reddy in 2006, Reddy showed by using F3 targeted nanoparticles that have both an imaging agent and a photosensitizer (Photofrin), Reddy could make brain gliomas sensitive to laser light irradiation with aims to target the cancer cells with the nanoparticles and the laser light, killing 90% of cancer cells present, which opens the door for possible use of laser light to kill cancer cells after treatment with the nanoparticles [10].

Overall, final evaluation of this paper by H. Tam; This paper gives great insights into new nanoparticles, targeting therapies, delivery mechanisms and strategies being developed and researched in recent years. Non-invasive methods appear to be the most important strategy for the treatment of CNS related diseases, according to Tam, as they display less adverse health effects and risk to the patient than invasive strategies, although research is still on going. This paper was very informative and gives great insights into the types of nanocarriers and targeting mechanisms in development within the field of drug delivery.



[1] – Vivienne H. Tam. (2016). Nanomedicine as a non-invasive strategy for drug delivery across the blood brain barrier. International Journal of Pharmaceutics. 515 (n/a), 331-342.

[2] – Lindsey Crawford. (2015). Concepts, technologies, and practices for drug delivery past the blood– brain barrier to the central nervous system. Journal of Controlled Release. 240 (n/a), 251-266.

[3] – Imre Mager. (2016). Targeting blood-brain-barrier transcytosis e perspectives for drug delivery. Neuropharmacology. XXX (n/a), 1-4.

[4] – S. Aday. (2016). Stem Cell-Based Human Blood–Brain Barrier Models for Drug Discovery and Delivery. Cell Press – Trends in Biotechnology. 34 (5), n/a.

[5] – Kelsie F. Timbie, Brian P. Mead, Richard J. Price. (2015). Drug and gene delivery across the blood–brain barrier with focused ultrasound. Journal of Controlled Release. 219 (n/a), 61-75.

[6] – Neuroscientifically Challenged. (2015). 2-Minute Neuroscience: Blood-Brain Barrier. Available: Last accessed 04/04.2017.

[7] – Frank J. Malinoski. (2014). The nanomedicines alliance: an industry perspective on nanomedicines. Nanomedicine: Nanotechnology, Biology, and Medicine. 10 (n/a), 1819-1820.

[8] – I. Fernandez-Piñeiro. (2017). Nanocarriers for microRNA delivery in cancer medicine. Biotechnology Advances. 35 (1.2. Nanomedicine in cancer treatment), 350-360.

[9] – David Fortin. (2007). Enhanced Chemotherapy Delivery by Intraarterial Infusion and Blood-Brain Barrier Disruption in the Treatment of Cerebral Metastasis. American Cancer Society. n/a (Results), 751-760.

[10] – G. Reddy. (2006). Vascular Targeted Nanoparticles for Imaging and Treatment of Brain Tumors. Clinical Cancer Research. 12 (n/a), 6677-6686.

A critical review of the research paper wrote by Robert Langer – “Where a pill won’t reach – How to get drugs where they need to go” for the Scientific American, Inc in 2003.

This paper was written by Professor Robert Langer of MIT, who has written and published over 1300 scientific articles in the fields of Drug Delivery, Chemistry, Biotechnology, and pharmaceuticals, making him the most cited engineer in History [1]. The central purpose of this article is to outline the route in which different drugs take to navigate through the body and retain their pharmacodynamic functions. The article outlines the process in which drugs are designed and administered to the body, to give the reader an understanding of the different limitations that different methods encounter, such as “Getting past the Gut”, “Penetrating the skin”, “Entering the Lungs” and “Controlling Release” [2]. Langer’s article is laid out in a hard to read fashion, but displays brilliant insights into the drug delivery field in the areas he covers.

R. Langer

Figure 1 – Robert Langer

In the introductory paragraph of the article, a statement is made that “pills can be coated with a shell that protects them against the stomach secretions due to the insolubility of the shell, but dissolves readily once the pill has reached a more alkaline environment in the small intestine”. Langer goes on to state that if the drug is made of proteins, by which most biotechnological agents are, that the drug also needs to be able to avoid the protein destroying enzymes called proteases. Drugs that are coated also presented the problem of limited control on their pharmacokinetics. Langer suggests coating the drugs in their own bodyguards, but proceeds to state that the drugs will then be too large to cross through the gut lining and into the bloodstream. Langer’s arguments show that his ideas were before their time, and it can be seen from a paper conducted in 2014, by Kinam Park, about “the controlled drug delivery systems, past, present and future”, that the development of new drug delivery systems requires consideration of multiple parameters, such as the drugs starting point or administration, delivery route, drug release kinetics and materials within the drug, before the drug can ultimately be used in human patients [3]. Langer’s methods were correct, and were the basis for what the field of drug delivery is now, as he was investigating the parameters involved to deliver the most optimal dose of a drug through the most effective drug delivery system specific to the target area.


Figure 2 – Overview of drug delivery systems from basic research to clinical applications

Figure 1 offers an overview of drug delivery research from an article published in 2014. This article was written 12 years after Langer’s paper, and as can be seen from the image, Drug delivery systems that Langer was focused on, are still the core parameters involved in present drug delivery systems. Langer’s ideas were focused on release kinetics and pharmacokinetics, which, as can be seen from Figure 2, are all interlinked with eachother. Langer stated that all aspects of drug delivery needed to be accounted for when developing a new drug delivery system, and this principle is still essential in the present day research being conducted in the field [3].


Figure 3 – Diffusion as a Drug Release Mechanism

Langer offers solutions to solve the issue of penetrating the gut’s intestinal wall, which were quite innovative and effective for a paper wrote in 2002, as Langer’s suggested methods such as bioadhesive polymer coatings that allow the drug to bind to the gut lining and squeeze between the cells, linking the drugs with carrier molecules in order to be taken up by the cells receptors and passed through into the bloodstream, linking drugs to targeting molecules that aim to bind with cell receptors on the intestinal cells, which pass the drug through the cells, in order to be taken up by the bloodstream. Langer identified the parameters in which may directly affect the delivery of the drug through the gut, but failed to account for the changing physiological environment of the fed gut, the physiochemical interactions between the drug and the fed gut, and the characteristics of the fed gut. There are still gaps in the knowledge related to the exact effects in which food and alcohol have in the gut environment, which Langer doesn’t account for in his assessment of “Getting Past the Gut”, but more recent studies in drug delivery systems are trying to account for by using in-silico and in-vitro testing with similar environments and parameters [5].


Figure 4 – Gastrointestinal physiology [5]

When comparing this method to more advanced drug delivery systems in recent years, a study wrote in 2015 by Ritu Goyal, about “Nanoparticles and Nanofibers for topical drug delivery” detailing the use of iontophoresis as a method for drug delivery through the skin, which uses physical enhancers such as ultrasound to temporarily disorder the skins Stratum Corneum, which is the principal barrier to drug diffusion, to increase the ability to administer the drug by up to 5000 times. Although effective, this drug delivery system has been said to be invasive and cause damage to the skins barrier properties in the long term, while causing numerous side effects [4].

Langer suggests that the lungs are an excellent route to pass drugs through to reach the bloodstream, and goes into details about the difficulties in designing inhaler devices that can administer sufficient amounts of aerosol particles that can penetrate the lung deeply, while making the statement, that lung administered drugs only deliver less than 10% of their contents. In recent years, formulation strategies to sustain drug release in the lungs has been focused on, with advancements coming in the ability to enhance the drug residence time in the lungs, protect the drug against degradation, and release the drug in a controlled manner at a therapeutically optimal rate [6]. Langer’s Suggestions that the lowering of the density of the particles present in the drugs while increasing their size and porosity proved to be another ahead of its time proposal, as new drugs such as microparticles and nanomedicines are being designed to be administered through the lungs due to their aerodynamic properties [6].

Finally, the development of drug delivery systems that have the ability of controlling release may be the most important aspect of this paper that Langer introduces to the field of drug delivery. Langer goes into detail about the control of the therapeutic level of the drug in the body without the need for frequent administration, and offers a solution of gold capped microchips that can be dissolved by electrical charges to release the drug inside the microchip at the desired times. Langer’s innovative mind set is one of his strongest qualities, as he had the ability to look ahead and propose ideas that are still being researched and developed in modern times.

Langer’s main points to take from this articles were the aspirations of developing drugs that could be administered at any time, at the correct dosage, anywhere in the body with specificity and efficacy. Through Langer’s research and suggestions, modern drug delivery systems have been developed and based off technologies and idea’s that Langer proposed, which is why Robert Langer is known as possibly the most successful chemical engineer in the drug delivery field.


[1] – Langer Labs. (06/01/17). Professor Robert Langer. Available: Last accessed 09/03/17.

[2] – Robert Langer. (2003). Where a pill won’t reach. Scientific American. n/a (n/a), 50-57.

[3] – Kinam Park. (2014). Controlled drug delivery systems – Past, Present and Future. Journal of Controlled Release. 190 (n/a), 3-8.

[4] – Ritu Goyal. (2015). Nanoparticles and Nanofibers for Topical drug delivery. Journal of Controlled Release. 2040 (n/a), 77-92.

[5] – F.J.O Varum. (2013). Food, Physiology and Drug Delivery. International Journal of Pharmaceuticals. n/a (n/a), n/a.

[6] – Cristina Loira-Pastoriza. (2014). Delivery strategies for sustained drug release in the lungs. Advanced Drug Delivery Reviews. 75 (n/a), 81-91.