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Itís all in the delivery
From patches and injections and self-delivering RNAi and nanodrills—covering the range from cardiology to nausea to cancer—we have quite the list of drug delivery refinements and breakthroughs to share with you from spring through summer of this year.
Cell-penetrating ‘nanodrills’ show promise for intracellular drug delivery
PORTLAND, Ore.—Although it’s our oldest piece of news for this roundup, from March, it’s also perhaps the most novel bit of news too, so we will start with researchers at Oregon State University (OSU) and Oregon Health & Science University (OHSU), who have created new nanomaterials able to cross cell membranes, establishing a novel platform for the intracellular delivery of molecular drugs and other cargo.
The researchers explored materials known as cell-penetrating self-assembling peptide nanomaterials, or CSPNs, using sequential ligation of peptide building blocks to create CSPNs that formed distinct shapes resembling a drill bit—these “nanodrills” reportedly showed a strong capacity for encapsulating guest molecules for therapy or imaging. Findings were published in the Journal of Controlled Release, and a provisional patent application was filed with the U.S. Patent and Trademark Office.
“CSPNs represent a new modular drug delivery platform that can be programmed into exquisite structures through sequence-specific fine-tuning of amino acids,” said corresponding author Gaurav Sahay, assistant professor of pharmaceutical sciences at the OSU/OHSU College of Pharmacy. “The fine-tuning of amino acids imparted versatile properties like flexibility, self-assembly, higher drug loading, biodegradability and biocompatibility for effective intracellular delivery of CSPNs.”
The Sahay lab team and collaborators, including researchers from the OHSU School of Medicine and the University of California, San Diego, generated five different CSPNs, conjugating Tat peptides to a (RADA)2 linker and adding different numbers of phenylalanine residues.
“We chose (RADA)2 because it contains alternating amino acids that repel water and mix with water; that imparted the property of self-assembly,” said first author Ashwani Narayana, postdoctoral scholar in the College of Pharmacy. “We demonstrated the transition of secondary structure in these CSPNs, which in turn played a vital role in self-assembly and drug delivery potential. The in-vivo efficacy of these nanodrills will extend the frontiers beyond intracellular delivery.”
These nanodrills reportedly demonstrated a high capacity to encapsulate hydrophobic guest molecules, and coarse-twisted nanodrills in particular were able to localize rapamycin in the liver in a mouse model. Rapamycin is an antifungal metabolite of the Streptomyces hygroscopicus bacterium and among its many properties is the ability to induce autophagy—the regulated, orderly degradation and recycling of cellular components. Defects in autophagy lead to accumulation of toxic materials in various disease conditions ranging from infectious diseases to neurodegenerative disorders.
“These modular CSPNs could be a new platform for delivering molecules across biological barriers thought to be impenetrable,” Sahay said. “And minute changes can direct self-assembly into myriad defined nanostructures, making them ideal hosts for a range of different molecules.”
Zosano announces positive data for ADAM technology
FREMONT, Calif.—In July, Zosano Pharma, a clinical-stage biopharmaceutical company developing and commercializing targeted therapies that deliver rapid systemic absorption using a novel and proprietary technology called Adhesive Dermally-Applied Microarray (ADAM), announced the recent publication of a peer-reviewed paper regarding ADAM technology for the delivery of zolmitriptan in the Journal of Pharmaceutical Science.
“This study enabled us to understand the delivery and tolerability of M207 in a nonclinical setting so as to aid us in setting reasonable expectations of our platform when studying in human subjects,” said Hayley Lewis, senior vice president of operations at Zosano Pharma. “The results from this animal study add to a growing body of evidence which indicate that absorption through the epidermis or dermis seems to be a suitable delivery platform for products that have limitations when delivered orally.”
Aequus and Corium team up against nausea
VANCOUVER, British Columbia—Specialty pharmaceutical company Aequus Pharmaceuticals Inc. recently announced an expansion of its relationship with Corium International Inc. to include the company’s long-acting transdermal patch, AQS1303, for the treatment of nausea and vomiting in pregnancy. Under the terms of the agreement, Corium will use its Corplex technology to improve the clinical performance of AQS1303 and will be the exclusive clinical and commercial manufacturer for the product.
“The momentum of our anti-nausea program continues to build with this collaboration. We had multiple parties express interest in the commercial manufacturing rights as we continue to advance this program,” said Doug Janzen, CEO and Chairman of Aequus.
Newest generation of heart stent approved
ABBOTT PARK, Ill.—Abbott announced this spring that it had received approval from the U.S. Food and Drug Administration (FDA) for XIENCE Sierra, the newest generation of the company’s XIENCE everolimus-eluting coronary stent system. Design and technology advances in this generation of XIENCE include features specifically designed for the treatment of complex blockages that now account for up to 70 percent of cases.
“We developed XIENCE Sierra so that physicians can more easily deliver the stent even in challenging cases,” said Chuck Brynelsen, senior vice president of Abbott’s vascular business. “The updated design and improved deliverability mean doctors can access and unblock difficult-to-treat lesions with more flexibility and precision than other stents.”
Self-delivering RNAi for immuno-oncology
MARLBOROUGH, Mass.—In May, RXi Pharmaceuticals Corp. announced that it had entered into a research collaboration with Iovance Biotherapeutics to evaluate the potential synergies with RXi’s novel sd-rxRNA therapeutic compounds and Iovance’s autologous cell therapy based on tumor-infiltrating lymphocytes (TILs) for the use in the treatment of cancer.
“Iovance is the leading company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology. Our agreement will allow Iovance to explore their proprietary TIL technology and our proprietary sd-rxRNA technology,” explained Dr. Geert Cauwenbergh, president and CEO of RXi Pharmaceuticals. “Under this research collaboration, we will further investigate and expand the recently published data with TIL and sd-rxRNA products, which demonstrated potentially enhanced tumor killing activity of TIL.
“As such, we may be able to improve potency of the TIL product and also possibly broaden the applicability of TIL in other tumors types. We see this new research collaboration with the highly experienced Iovance team using TIL, as a major step to advance life-saving treatment approaches for solid tumors, a space where there is still a dire need for improved therapies for these patients.”
Creating cannabinoid delivery technologies
SEATTLE—Cannabis Leaf Inc., a developer of medical products, nutraceuticals and formulation and delivery technologies for the healthcare and consumer care industry, announced in the spring that it had entered into a merger agreement with Apotheca Biosciences Inc., with the surviving corporation to be Apotheca Biosciences.
Apotheca Biosciences also develops medical products, nutraceuticals and formulation and delivery technologies , and its pipeline of products includes transdermal, sublingual and nasal delivery technologies for precise and controlled dosing of cannabinoids.
Apotheca Biosciences calls itself “a pioneering biotech company with an emphasis on research and development in addition to the creation of high-grade nutraceuticals and cosmetics” and its goal is to lay the groundwork and continue research of cannabinoid receptiveness in patients and create nutraceuticals that reflects that research.