Delivering Complex Drugs With Nanotechnology-Based Solutions - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Delivering Complex Drugs With Nanotechnology-Based Solutions
Parenteral drug delivery offers a variety of challenges but also opportunities.


Pharmaceutical Technology
Volume 37, Issue 5, pp. s32-s34

Nanolipogels as drug-delivery vehicles

Researchers at Yale University developed nanolipogels as a new drug transport technology to deliver anticancer therapies. The nanolipogels are nanoscale, hollow, biodegradable spheres, which are capable of holding chemically diverse molecules, according to a July 15, 2012 press release by the National Science Foundation (NSF), which is providing funding for the research. The nanolipogels contained transforming growth factor (TGF-β) and interleukin-2 (IL-2). Specifically, the researchers developed nanoscale liposomal polymeric gels (i.e., nanolipogels) of drug-complexed cyclodextrins and cytokine-encapsulating biodegradable polymers to deliver small hydrophobic molecular inhibitors and water-soluble protein cytokines. The nanolipogel releasing TGF-β inhibitor and IL-2 significantly delayed tumor growth, increased survival of tumor-bearing mice, and increased the activity of natural killer cells and of intratumoral-activated CD8+ T-cell infiltration (3, 4).

“The cytokine can be thought of as a way to get reinforcements to cross the dry moat into the castle and signal for more forces to come in,” said Fahmy in the NSF release. “In this case, the reinforcements are T-cells, the body’s anti-invader ‘army.’ By accomplishing both treatment goals at once, the body has a greater chance to defeat the cancer,” he said.

An important aspect of the nanolipogels is their ability to “package” two completely different kinds of molecules--large, water-soluble proteins, such as IL-2, and smaller water-phobic molecules, such as the TGF-β inhibitor--into a single delivery vehicle, according to the NSF release. The outer shell of each nanolipogel is made from a biodegradable, synthetic lipid that degrades in a controlled manner, can encapsulate a drug-scaffolding complex, and is easy to form into a spherical shell. Each shell surrounds a matrix made from biocompatible, biodegradable polymers that are impregnated with the TGF-β inhibitor molecules. Those near-complete spheres are put in a solution containing IL-2, which gets entrapped within the scaffolding, a process called remote loading, according to the NSF release. The result is a nanoscale drug-delivery vehicle that is small enough to travel through the bloodstream but large enough to be entrapped for delivery to the tumor sites (3, 4).

Nanoparticles for protein synthesis

Researchers at the Massachusetts Institute of Technology (MIT) developed nanoparticles that can be controllably triggered to synthesize proteins. The hope is that particles could be used to deliver small proteins that kill cancer cells and eventually larger proteins such as antibodies that trigger the immune system to destroy tumors. The nanoparticles consist of lipid vesicles filled with the cellular machinery responsible for transcription and translation, including amino acids, ribosomes, and DNA caged with a photo-labile protecting group. These particles served as nanofactories capable of producing proteins including green fluorescent protein (GFP) and enzymatically active luciferase.

In vitro and in vivo protein synthesis was spatially and temporally controllable and could be initiated by irradiating micron-scale regions on the timescale of milliseconds (5).

The researchers designed the new nanoparticles to self-assemble from a mixture that includes lipids, which form the particles’ outer shells, plus a mixture of ribosomes, amino acids, and the enzymes needed for protein synthesis. Also included in the mixture are DNA sequences for the desired proteins. The DNA is trapped by DMNPE, which reversibly binds to it. This compound releases the DNA when exposed to ultraviolet light. In this study, particles were programmed to produce either GFP or luciferase. Tests in mice showed that the particles were successfully prompted to produce protein when UV light shone on them, according to an Apr. 9, 2012 MIT press release. Although more testing must be done to show that the nanoparticles can reach their intended destination in humans and that they can be used to produce therapeutic proteins, the research is an interesting start. The researchers are working on particles that can synthesize potential cancer drugs by targeting protein production that could be turned on only in the tumor, thereby avoiding side effects in healthy cells. The team also is working on new ways to activate the nanoparticles. Possible approaches include production triggered by acidity level or other biological conditions specific to certain body regions or cells, according to the MIT release.

Gold nanoparticles

Researchers at the University of Sydney in Australia, led by Nial Wheate, senior lecturer in the Faculty of Pharmacy, and researchers from the University of Strathclyde and the University of Glasgow in Scotland recently reported on delivering the anticancer drug cisplatin using gold-coated iron oxide nanoparticles for enhanced tumor targeting (6, 7). The researchers used this approach to overcome some challenges of cisplatin, namely poor bioavailability, severe dose-limiting side effects, and rapid development of drug resistance. The iron oxide core was coated in a protective layer of gold before the anticancer drug cisplatin was attached to the gold coating using spaghetti-like strings of polymer, according to a May 31, 2012 University of Sydney press release.

The iron oxide nanoparticles (FeNPs) were synthesised via a coprecipitation method before gold was reduced onto its surface (Au@FeNPs). Aquated cisplatin was used to attach {Pt(NH3)2} to the nanoparticles by a thiolated polyethylene glycol linker forming the desired product (Pt@Au@FeNP). The nanoparticles were characterized by dynamic light scattering, scanning transmission electron microscopy, UV visible spectrophotometry, inductively coupled plasma mass spectrometry, and electron probe microanalysis. Nanoparticle drug loading was found to be 7.9 10-4 moles of platinum per gram of gold. External magnets were used to show that the nanoparticles could be accumulated in specific regions and that cell-growth inhibition was localized to those areas (6, 7).

References

1. C. Bonnaud et al., IEEE Transaction on Magnetics 49 (1), 166-171 (2013).

2. P. Van Arnum, Pharm. Technol. Sourcing and Management, Feb. 6, 2013.

3. T. Fahmy et al., Nature Materials, online, DOI:10.1038/nmat3355, July 15, 2012.

4. P. Van Arnum, Pharm. Technol. Sourcing and Management, Aug. 1, 2012.

5. A. Schroeder et al, Nano Lett., online, DOI: 10.1021/nl2036047, Mar. 20, 2012.

6. P. Van Arnum, Pharm. Technol. Sourcing and Management, June 6, 2012.

7. N. Wheate et al., Inorg. Chimica Acta, online, DOI10.1016/j.ica.2012.05.012, May 30, 2012.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
70%
Breakthrough designations
4%
Protecting the supply chain
17%
Expedited reviews of drug submissions
2%
More stakeholder involvement
7%
View Results
Eric Langerr Outsourcing Outlook Eric LangerTargeting Different Off-Shore Destinations
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerAsymmetric Synthesis Continues to Advance
Jill Wechsler Regulatory Watch Jill Wechsler Data Integrity Key to GMP Compliance
Sean Milmo European Regulatory WatchSean MilmoExtending the Scope of Pharmacovigilance Comes at a Price
From Generics to Supergenerics
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Ebola Outbreak Raises Ethical Issues
Better Comms Means a Fitter Future for Pharma, Part 2: Realizing the Benefits of Unified Communications
Better Comms Means a Fitter Future for Pharma, Part 1: Challenges and Changes
Source: Pharmaceutical Technology,
Click here