Recent research into the structural development of infant lungs could have wider implications for nanoparticle drug delivery to infants.
Research emerging from a collaboration of researchers from the German Research Center for Environmental Health (Munich, Germany) and Harvard Medical School (Boston, MA, USA) has revealed new insights into inhaled nanoparticles in infant lungs. The research, published in a recent edition of PNAS, is the first of its kind and has implications for not only pulmonary drug delivery to infants, but also for the effect of pollution on their lungs.
The research team‘s aim was to study the effects of ‘chaotic mixing‘ on the deposition of inhaled nanoparticles. The theory of chaotic mixing describes the complex airflow within the lungs due to vortexes formed within the alveoli. The team chose to study this effect in infant lungs, since alveolar development is still occurring. They hypothesized that they would see the chaotic mixing effects materialize as the lungs developed.
The team measured particle deposition in vivo, in the lungs of infant rats. The rats ranged from newborn to 21 days old. This model system is seen as equivalent to the lung development in humans, from newborn to 2 years old. Apart from this differing time-scale, the researchers propose the structural change in developing lungs is essentially the same in rat and human systems, allowing them to draw certain conclusions.
The team elucidated that particle deposition in the lungs is initially very low and increased to a peak at 2 years. This coincided with the full development of the infant lung, with full alveolation having occurred (defined as the development of deep alveoli, from their initial shallow stage). The researchers‘ findings indicated a major structural change in the developing lungs, leading to an alteration in the airflow to the lungs.
This new research has numerous implications. In general, it shows that the airflow in infant lungs is not, as previously believed, a ‘miniature version‘ of adult lungs. Since particle deposition is highest in approximately 2 year olds, this may explain why children could be more susceptible to air pollution. Additionally, this new research should be taken into account when calculating dosage of pulmonary-delivered drugs. Speaking exclusively to Therapeutic Delivery, co-author Akira Tsuda from the Harvard School of Public Health (Boston, MA, USA) explains that he sees this “re-evaluation of inhaled drug dosage for the treatment of respiratory illness (e.g., currently, aerosolized β2 agonists are often used clinically for child asthma or other pulmonary disease treatment)” as one of the main implications of this work, since, “in the current treatment, the change of the postnatal airway structure is entirely ignored.”
Looking further into the future, since this research indicates a higher propensity to pulmonary drug delivery in small children, Tsuda suggests this may have far-reaching applications, “I am wondering whether we can vaccinate infants using the inhalation route. As the lung surface is large; it can work as an ideal site for immunization. An obvious advantage of the inhalation delivery is that it is non-invasive and can be easily applied for a large population.”
Looking forward, Tsuda explained his plans for future work. Building on previous work, he aims to study the absorption of nanoparticles into the infant alveolar epithelium and their subsequent delivery to their target organ.
– Written by Alice O‘Hare
Source: Semmler-Behnke M, Kreyling WG, Schulz H et al. Nanoparticle delivery in infant lungs. Proc. Natl Acad. Sci. USA 109(13), 5092–5097 (2012).
A study detailing an iota-carrageenan matrix encapsulating curcumin shows potential for the controlled release of unstable and hydrophobic nutraceuticals.
Researchers from Purdue University (IN, USA) have published work on a novel hydrocolloid matrix for encapsulation of a nutraceutical, which shows potential in the development of medicinal foods.
Neutraceuticals are defined as food (or food products) that are reported to provide a health benefit. Curcumin for instance, which was used in this study, is found in turmeric and has been reported to provide anti-inflammatory and anti-cancer properties. However, nutraceuticals are often unstable and hydrophobic, therefore much research has been carried out to find novel delivery systems for these molecules.
Srinivas Janaswamy and Susanne Youngren (IN, USA) describe their novel system in a recent edition of Food and Function. Using curcumin as a model nutraceutical, they encapsulated the molecules into a hydrocolloid matrix. The matrix comprised crystallized iota-carrageenan, trapping the curcumin molecules in a stable and hydrophilic matrix. The pair showed that their novel fiber maintained this organized structure and protected the curcumin molecules allowing controlled release.
Speaking exclusively to Therapeutic Delivery, Janaswamy describes other implications for their novel hydrocolloid system. He anticipates that it, “will lay a stimulating foundation for encapsulating nutraceuticals, flavor compounds, vitamins and drug molecules.” He continues, “The well-organized arrangement of hydrocolloid helices in the oriented fibers is deemed to serve as a stable platform during the actual delivery process and increase the bioavailability of embedded molecules, which in turn will aid in the design and development of value-added functional foods and medicinal foods.”
Janaswamy explains their plans for future work, “The mechanistic approach demonstrated in our article on the encapsulation of curcumin molecules in the sodium form of iota-carrageenan is quite convincing. However, we still need to determine the factors that control the achievable density, such as the maximum loading of molecules into the hydrocolloid matrix, as it determines the total amount of sample that can be used to reach therapeutic dose in biological studies.” He further explained that they aim to determine the effect of other charge-balancing cations on the hydrocolloid matrix and aim to study hydrocolloid matrices other than iota-carrageenan.
– Written by Alice O‘Hare
Source: Janaswamy S, Youngren SR. Hydrocolloid-based nutraceutical delivery systems. Food Funct. doi:10.1039/C2FO10281A (2012) (Epub ahead of print).
University of Cincinnati chemist describes preliminary work on chemotherapy agents that specifically target the reactive oxygen species created in a tumor environment.
In a recent news story on the University of Cincinnati (OH, USA) website, chemist Edward Merino from the university, describes his research into a “new generation of chemotherapy drugs.” He presented his findings at the conference ‘The Chemistry of Life: Spring National Meeting and Exposition of the American Chemical Society‘ (San Diego, CA, USA).
The aim of Merino‘s work is to find anticancer agents that avoid the side-effects of current chemotherapy drugs. These side-effects, such as hair- and weight-loss, are caused by the nonspecific targeting of cells. On administration of these chemotherapeutics, tumor cells are affected due to their fast-replicating nature; however so are other fast-replicating cells, which leads to these unwanted side-effects. In order to prevent this, Merino explains that other characteristics of the tumor environment need to be addressed.
Due to their differing metabolism, tumor cells release reactive oxygen species. This creates the environment that Merino and his team hope to target. As Merino describes, “We are looking for chemicals that operate like heat-seeking missiles that attack only cancerous cells. If we are successful, we can create drugs with far fewer side effects.”
At the conference, Merino presented a new anticancer agent that exploits this theory. Looking to the future, Merino and his team have one such agent moving into murine studies, as well as studying other agents that “look promising.”
–Written by Alice O‘Hare
Source: UC Researcher announces progress toward new chemotherapy agents (2012): www.uc.edu/news/NR.aspx?id=15402
Scientists from the Massachusetts Institute of Technology (MIT; MA, USA) monitored the release kinetics of human immunoglobulin (IgG) from the permeable structure of a two-layer nanofibrous self-assembling peptide hydrogel over a period of 3 months. The researchers found that varying the density of the hydrogel nanofibers affected the amount of IgG released, meaning that they were able to control the release kinetics. Sotirios Koutsopoulos, a research scientist at MIT and lead author of this research, described the aim of their work. “Our goal is to develop a system that provides sustained and controlled release of the therapeutic molecules. By varying the density of the peptide nanofibers we showed that the peptide hydrogel can release human antibodies from days to months. Furthermore, by creating a multi-layer and onion-like hydrogel system, we showed slow release of therapeutic molecules for up to 3 months.”
Recently, monoclonal antibody therapy has become increasingly important for effective therapies in a variety of diseases including cancer, multiple sclerosis and other neurodegenerative diseases. Thus this self-assembling peptide hydrogel sustained release medical technology will find a wide range of uses.
Koutsopoulos and his co-author Shuguang Zhang also observed that encapsulation in and release from the hydrogel structures did not affect the antigen-binding activity and conformation of the antibody, even after 3 months. The hydrogel designed by Koutsopoulos and Zhang is fully biocompatible and injectable, making it an ideal material, according to Koutsopoulos, for personalized therapies, “the peptide hydrogel system can be used by physicians or nurses with minimal training who can prepare the drug formulation and adjust the release of the therapeutic compound to the desired timeframe on site, simply by mixing the appropriate amount of peptide solution with the drug compound. This will address each patient‘s personal needs for optimal therapy because the patient will receive a treatment that will last as long as the prescription requires and optimal dosing, which will eliminate toxic side effects.”
The researchers also found that their hydrogel system allowed for 100% IgG loading efficiency, because the hydrogel itself is made up of 99.5% water. Therefore the maximum amount of drug or antibody loading in to the hydrogel depends solely on its solubility in water. Efficient drug loading is a challenge in drug delivery and Koutsopoulos hopes his system may be able to overcome this.
When explaining the next steps for this research, Koutsopoulos was aware that there is still a large amount of research to be done, “Future work will be focused on the release of therapeutic molecules like insulin to treat diabetes, hormones, growth factors, cancer drugs and eye medications. Furthermore, we want to explore the pharmacokinetics and biodistribution in animals and ultimately in humans.” However, he was optimistic about the future for this method of drug delivery, “The peptide hydrogel system has been tested in humans with success. This will facilitate the transfer of peptide hydrogel drug delivery technology from bench to bedside.”
–Written by Hannah Stanwix
Source: Koutsopoulos S, Zhang S. Two-layered injectable self-assembling peptide scaffold hydrogels for long-term sustained release of human antibodies. J. Control. Release doi:10.1016/j.jconrel.2012.03.014 (2012) (Epub ahead of print).
A new modality enabling the simultaneous control of shape memory polymer (SMP) and release of loaded drugs has been detailed in research published by a team of scientists from China and Canada. Their findings suggest that SMPs can be manipulated by ultrasound, allowing control over when and how drugs are released.
Lead researcher Hesheng Xia, from Sichuan University, Chengdu (China), explains that SMPs can be fixed into a temporary shape, then external stimuli can cause them to recover their original shape. “When a piece of polymer is placed in the body, it is subjected to heating at 37°C everywhere and the whole piece undergoes shape recovery” he adds.
As part of the present research, the scientists directed a high intensity focused ultrasound beam onto a specific area of polymer. This caused a local rise in temperature that triggered shape recovery that was limited to the area targeted. An additional benefit of the use of ultrasound is that it can easily penetrate body tissue.
The group also provides evidence illustrating spatial and temporal control of the shape-recovery process. The SMP sample was loaded with a drug and folded into a temporary ‘I‘ shape. The SMP could then be formed into a ‘V‘ and ‘N‘ shape, and back to the original ‘M‘ form, by directing the ultrasound onto different positions on the polymer. The process therefore gives SMPs the capability of forming multiple intermediate shapes, allowing the release of loaded drugs to be synchronized in a switchable way.
Drug release can be halted by the switching off of the ultrasound, which causes a rapid drop in temperature and allows the SMP to adopt a stable shape.
“Future challenges will involve developing ways to reduce the power and the irradiation time required for specific applications” commented Xia.
– Written by Lucy Marum
Source, Source: Li G, Fei G, Xia H, Han J, Zhao Y. Spatial and temporal control of shape memory polymers and simultaneous drug release using high intensity focused ultrasound. J. Mater. Chem. doi:10.1039/c2jm30848g (2012) (Epub ahead of print).