Ravikumar Majeti, PhD, a professor of pharmaceutical sciences at the Texas A&M Irma Lerma Rangel College of Pharmacy, and his team are working on a means around this problem. They think nano systems (tiny particles that can interact with cells) are the answer to delivering these types of difficult-to-administer drugs orally, and they think they’ve found a way, which they’ve reported in an article published in the journal Scientific Reports.

In many ways, the team has taken pieces of existing knowledge to formulate a new drug carrier. The research team’s overall approach, targeted nanosystem drug delivery, is a popular method in modern pharmacology, because tiny materials can get the drug where it is needed far better than traditional methods can.

The trouble is, the current methods of targeted drug delivery use ligands that have to out-compete the ligands that are naturally present in the body. On the other hand, Kumar’s team’s nanoparticles bind non-competitively, meaning the cells will still take up the particle even if they’re saturated with naturally occurring ligands. In order to achieve the non-competitive active transport, the Kumar team used gambogic acid, a natural product that is known for its ability to kill cancer cells.

“Our strategy is non-competitive active transport,” Kumar said. “These nanosystems have the ability to cross the intestinal barrier to reach other parts of the body and stay in circulation for a long time.” This ability to cross the intestinal barrier in sufficient quantities has been a major problem with oral medications–and part of why insulin, for example, is injected, not swallowed. In this case, the nanoparticle makes the body itself help the drug become absorbed.

“The way we put these things together is completely novel,” Kumar said. “This approach enables the development of carrier systems that have no equivalent in the world of competitive ligands.”

The system can also penetrate the blood-brain barrier, which could have important implications for drugs that need to reach the brain–to attack brain tumors, for example.

“We can fine-tune the nanosystems to match the disease in question,” said Ganugula Raghu, PhD, one of the researchers in Kumar’s lab and a co-author of the paper. “It is also relatively easy to adjust the timing of the drug release, either fast or slow, depending on the needs of the patient. For example, such systems can be designed to benefit diabetic patients by facilitating hepatic (liver) and peripheral insulin in a single dose.”

Exact concentrations of the active pharmaceutical and the ligand density on the particle can also be ‘tuned’ by controlling the ratios of functional to non-functional polymers. This can be thought of as similar to adding both real sugar (the ‘functional polymer’) and artificial sweetener (the ‘non-functional polymer’) to your iced tea. If you are trying to get exactly a certain number of calories, you can add more or less real sugar to get to that goal. To make the beverage the same consistency and sweetness, you would then add artificial, calorie-free sweeteners to make up the difference. The same basic theory applies to obtaining just the right amount of active medication.

“We really think these small particles will open up new avenues in receptor-mediated oral delivery of poorly soluble and permeable compounds that constitute about 40 percent of the new chemical entities requiring specialized delivery systems,” said Meenakshi Arora, PhD, another member of Kumar’s lab and paper co-author.

“I’m excited that this work is very translatable to the clinic,” added Prabhjot Saini, PhD, another lab member and co-author of the study. “Our work is very applicable to actual patients in need of live-saving medication–and they’re the reason we do what we do.”

“The current method of estimating water use is very arbitrary,” says postdoctoral scholar Elizaveta Litvak, first author on the new study, published in the Journal of Arid Environments. “And there has been no scientific ground for more precise recommendations.”

Field of steam

Scientists study how much water plants lose so that landscape managers can know how much water they need to put back in. Water evaporates in a straightforward physical process that depends primarily on the temperature and humidity of the air. But plants also lose water through transpiration, breathing out water vapour as part of their metabolism. Transpiration is less predictable, because it’s controlled by the plant’s biological processes. Plants may restrict transpiration in drought conditions, for example. Transpiration rates can also vary from species to species. The combined measure of evaporation and transpiration is called “evapotranspiration” (ET) and it’s a difficult quantity to measure. “There is no direct way to measure it,” Litvak says. “It’s like trying to capture what’s not capture.”

Researchers attempt to determine a crop’s ET rates by placing a large greenhouse-like chamber over an area of plants and measure how temperature and humidity changed within the chamber. But the presence of such a large chamber changes the plants’ environment so much that the method is far from ideal.

The current state-of-the-art method involves placing tall towers, festooned with scientific instruments, in large crop fields. The towers measure slight atmospheric changes multiple times per second, and researchers feed the data into a mathematical model to compute ET rates for that field.

The lawns of LA

The present-day turfgrass ET model serves for estimating water use by forests and agricultural crops in various weather conditions. Urban lawns, however, are much smaller than crop fields. Although turf grass is the largest irrigated crop in the U.S., researchers aren’t certain how the ET model holds up in the fragmented urban landscape. Tall water vapor flux towers are not the answer. “You can’t use that method in urban lawns because they’re too small,” says U biology professor Diane Pataki. “It just can’t be done where lawns form a patchwork with streets and buildings. People hadn’t gone in to cities and measured what turf grass was actually doing.”

Urban lawns present challenges to the model. First, urban environments create heat islands as air heats up in developed areas like parking lots. The hot dry air likely enhances evaporation rates and changes plant water responses, compared with natural and agricultural settings. Second, shade from landscape trees and buildings may create the opposite effect and mitigate ET rates, perhaps on an hourly basis.

Yet, as the best method available, the turfgrass ET model is the foundation of California’s watering recommendations and guides the actions of advanced irrigation systems via nearby weather stations. “That’s the gold standard in California for watering,” Pataki says.

Because of the impracticality of building water vapor flux towers in residential lawns, Pataki and Litvak turned to the simple chamber method for measuring ET. They built a small clear box a bit bigger than a shoebox equipped with sensors that would instantaneously measure temperature and humidity within the box and, when set on a lawn, would provide a rapid estimate of ET. They carefully calibrated the method by weighing lawn pieces on a precise scale to capture weight losses caused by ET. Litvak says that she got some puzzled looks and questions while toting the mini-chamber around the LA area. Some asked if it was a science fair experiment. “It looks so primitive,” she says of the box. “It looks so simple.”

Throw some shade

Litvak and Pataki found that their measurements of turfgrass ET didn’t always match modeled predictions. The model’s recommendations for watering shaded lawns are very vague, Pataki says, and most lawns are shaded, to some degree at some parts of the day by trees or buildings. Shade dramatically reduces plants’ water needs, so a partly-shaded lawn will need less water than unshaded.

The model also doesn’t account for the Santa Ana winds, masses of hot dry air that periodically tumble out of the mountains and through the LA area. Temperatures go up and humidity plummets. “The models can’t deal with that at all,” Pataki says. “They predict very high ET, but not as high as what we observed during those time periods.”

Litvak says that the model performs best on dense unshaded grass, possibly intentionally overwatered to keep it green. On such lush lawns, actual ET is very close to predicted. Litvak and Pataki developed an approach to adjust ET rates for different urban conditions, including dry air or partial shade, that could lead to adjusted watering recommendations. “At some level, modeled methods work,” Litvak says. “But when we transition to really low humidity, they just don’t match our findings.”

“The water use we measured in the field was higher than the recommendations that California was already making,” Pataki says. “So if all people did was follow the recommendations, that’s a significant water savings right there. Plus the recommendations could be improved as well.”

On home turf

Turf grasses in California are typically fescue or Bermuda grass species, instead of the Kentucky blue grass that’s common in Utah. While the precise ET numbers may not be directly applicable in Utah, the general lessons of the study hold. Pataki and Litvak have one resounding suggestion for managing your grass in the summer: “Shade your lawn!” Then dial back irrigation water use accordingly.

“Do you know how much water you use to irrigate your lawn?” Litvak says. Many people don’t, including landscape managers she interviewed in her research. Utah water managers recommend two irrigation per week in early and late summer and three irrigation in the hottest months. Each irrigation should deliver half an inch of water, which should take 20-40 minutes, depending on the sprinkler system type.

“A lot of the lawn space we see in people’s yards doesn’t seem to be used for anything other than aesthetics,” Pataki says. “So that is going to cost some water.”

The urban jungle

Litvak’s doctoral dissertation work, of which this study is a continuation, results in an upcoming analysis of water use by plants in the entire LA area, including the “urban forest” of trees. The analysis, once completed, will be the first of its kind, a large-scale transpiration measure that can be applied to other urban areas as well.

“If you look out at this landscape in Salt Lake, how much water is coming off of this vegetation?” Pataki says, gesturing at her office window that overlooks the bustling Salt Lake Valley, covered with a canopy of trees. “No one knows.”

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