Polymeric nanoparticles that are easily modified and can carry therapeutic and diagnostic agents deep into the lung can also be made biocompatible and have localized action with few side effects, according to research published in Acta Biomaterialia this month. [J U Menon et al, 2014, Acta Biomaterialia, online; DOI: 10.1016/j.actbio.2014.01.033]
Kytai Nguyen of The University of Texas at Arlington, Arlington and the Southwestern Medical Center at Dallas and colleagues point out that there have been no studies investigating the details of such nanoparticles for the delivery of protein or nucleic acids to the lung.
They have now studied six polymeric NPs: gelatin, chitosan, alginate, poly(lactic-co-glycolic) acid (PLGA), PLGA–chitosan and PLGA–poly(ethylene glycol) (PEG), as carriers for protein or DNA that can be delivered to the patient by inhalation. The researchers tested particle uptake by human alveolar type-1 epithelial cells in vitro as well as inhalation of a nanoparticles bearing DNA encoding for yellow fluorescent-tagged and nanoparticles encapsulating rhodamine-conjugated erythropoietin in laboratory rats.
They demonstrated that PLGA-based and natural polymer nanoparticles made from gelatin, for instance, were the most biocompatible with the live cells and gave the best dose-dependent in vitro uptake. They also showed that a single inhalation of the nanoparticles was able to induce widespread distribution of the erythropoietin in the rat lung, which persisted for up to ten days. Similarly, they could see yellow fluorescent protein being expressed continuously by the encapsulated DNA in the rat lung for up to a week.
Given that conventional methods of delivering biological agents to the lung are limited by toxicity, low bioavailability and instability issues, the team's findings suggest that nanotechnology might represent the way forward in this area of research. Moreover, inhalation is a non-invasive delivery route, avoids the issues of oral agents having to pass through the harsh and denaturing environment of the alimentary tract. The size of the optimal nanoparticles - 160 and 187 nanometers for PLGA and gelatin, respectively) are amenable to nebulization while being too small to trigger an attack from white blood cells, phagocytes, in the alveolar pockets of the lung.
The researchers point out that their work highlights an important point in that the results differ between in vitro and in vivo experiments. Although greater cellular uptake of natural polymer-based nanoparticles was observed in vitro, the in vivo tissue distribution profiles following nebulization were relatively similar for both PLGA and gelatin particles. It will, therefore, be necessary for future research not to make assumptions about the properties of a given nanoparticle based solely on in vitro tests.
"Our future work will determine the optimal therapeutic dose and frequency of administration as well as the local and systemic effects of specific encapsulated therapeutic reagents following nanoparticle delivery to facilitate lung regeneration," Nguyen told Materials Today.
David Bradley blogs at http://www.sciencebase.com and tweets @sciencebase, he is author of the popular science book "Deceived Wisdom".