The researchers showed that thioketal nanoparticles have the chemical and physical properties needed to overcome the obstacles
of gastrointestinal fluids, intestinal mucosa, and cellular barriers to provide therapy to inflamed intestinal tissues. The
researchers are currently working on increasing the degradation rate of the nanoparticles and enhancing their reactivity with
reactive oxygen species. The team also plans to conduct a biodistribution study to detail how the nanoparticles travel through
the body.
"Polymer toxicity is something we'll have to investigate further, but during this study, we discovered that thioketal nanoparticles
loaded with siRNA have a cell-toxicity profile similar to nanoparticles formulated from the FDA-approved material poly(lactic-co-glycolic
acid)," said Murthy in the press release. In the future, thioketal nanoparticles may become a significant player in the treatment
of numerous gastrointestinal diseases linked to intestinal inflammation, including gastrointestinal cancers, inflammatory
bowel diseases and viral infections, according to Murthy.
In other work, researchers from the University of Texas at Austin used nanoparticles in oral drug delivery to the colon. They
noted that oral drug delivery to the colon is a difficult, but desirable method of administration. A dosage form to the colon
must overcome several challenges, including barriers in the gastrointestinal tract. These challenges may include a steep pH
gradient, binding to the mucus layer, premature clearance, and premature cellular uptake. The researchers reported on nanoparticles
that have been designed to address these problems. These areas include drug entrapment with particle coating, surface modification,
drug adhesion to a nanoparticle surface, and nanogel systems to target drug delivery to the colon following oral administration.
Nanoparticles may be further used to target specific cells in the colon, such as tumor cells or inflamed tissues (2). Converting
a drug powder into nanoparticles can often solubilize a compound that is poorly soluble in water or increase bioavailability
through an increase in the surface-area-to-volume ratio. Smaller particles mean a bigger surface area to interact with absorbing
surfaces in the gastrointestinal tract.
In addition to advancing oral drug delivery, nanotechnology can play an important role in all routes of administration by
addressing specific problems, such as poor solubility. Poor solubility is particularly problematic when developing anticancer
therapeutics because the goal is to achieve clinical efficacy while limiting the dosage of chemotherapeutic agents. To address
this issue, researchers at Northwestern University in Evanston, Illinois, recently used nanodiamond-mediated delivery for
several water-insoluble drugs. In their study, the researchers reported that nanodiamonds enhanced the water dispersion of
three anticancer agents: purvalanol A, a treatment for liver cancer; 4-hydroxytamoxifen, a drug to treat breast cancer; and
dexamethasone, an antiflammatory agent to treat complications from certain types of cancer (3, 4).
The researchers showed that the water-insoluble compounds interact with the nanodiamonds, a biocompatible material, and form
complexes that disperse the drug in water for sustained periods of time, while maintaining the functionality of the drug.
Nanodiamonds are a class of nanomaterials, 4–6 nm in diameter in single-particle form, that can be manipulated to form clusters
with diameters in the range of 50–100 nm. This composition makes them suitable for drug delivery by shielding and slowly releasing
drugs that are trapped with the clusters of the diamond aggregates. Benefits in drug delivery from the nanodiamond cluster
include the capability of trapping more drug in the nanodiamond cluster compared with conventional drug-delivery methods and
easy dissolution of the nanodiamond in water. Nanodiamonds' surfaces are functionalized with carboxyl groups that promote
their dispersibility in water.
References
1. D.S. Wilson et al., Nat. Mater.
9 (11), 923–928 (2010).
2. K. O' Donnell and R.O. Williams, Int. J. Nanotechnol.
8 (1–2), 4–20 (2011).
3. P. Van Arnum, Pharm. Technol.
34 (1), 48 (2010)
4. D. Ho et al., ACS Nano
3 (7), 2016–2022 (2009).
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