NanoViricides Inc. (NNVC)

[Ubertino]

I hope to see NNVC involved in this sort of siRNA delivery vehicle some day:

Pub. No.:
WO/2014/059430
International Application No.:
PCT/US2013/064887
Publication Date:
17.04.2014
International Filing Date: 14.10.2013

Applicants:
BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM [US/US]; 201 W. 7th Street Austin, TX 78701 (US)

Inventors:
PEPPAS, Nicholas; (US).
LIECHTY, William; (US)

DELIVERY OF SMALL INTERFERING RNA AND MICRO RNA THROUGH MEMBRANE-DISRUPTIVE, RESPONSIVE NANOSCALE HYDROGELS

STATEMENT OF GOVERNMENT INTEREST

[01] This invention was made with government support under Grant No. CBET 10-33746 awarded by the National Science Foundation. The government has certain rights in the invention.

CROSS-REFERENCE TO RELATED APPLICATION

[02] This Application claims the benefit of U.S. Provisional Application Serial No. 61/713,610 filed on October 14, 2012, which is incorporated by reference.

BACKGROUND

[03] Polymers have played an integral role in the advancement of drug delivery technology, providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and enabling tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In particular, hydrogels have been instrumental in the development of polymeric systems for controlled release of therapeutic agents. These materials are attractive for transmucosal and intracellular drug delivery because of their facile synthesis, inherent biocompatibility, tunable physicochemical properties, and capacity to respond to various physiological stimuli.

[04] The landmark discovery of RNA interference (RNAi) in 1998 has sparked a massive research effort in all fields of biological science and redefined our understanding of gene regulation mechanisms. Theoretically, RNAi mediated by small interfering RNA (siRNA) could be used as a powerful and versatile treatment modality to treat nearly any disease resulting from aberrant gene expression. Owing to its remarkable potency and low therapeutic dosage, siRNA holds extraordinary promise as a new biological therapeutic. However, efficient delivery has been implicated as the major hurdle to its widespread clinical application. Although much effort has been directed toward synthetic polymer carriers for siR A, there remains a paucity of data on the development of oral delivery systems. Nearly all delivery systems undergoing clinical trials (no RNAi therapeutic has achieved FDA approval) rely on naked siRNA, conjugated polymers, or lipid carriers for topical and intravenous administration and do not posses attributes that render them useful delivery vectors for GI targets. It is desirable to develop a novel hydrogel platform for siRNA delivery, a synthetic polymer carrier capable of providing siRNA to disease targets, especially those along the gastrointestinal tract.

SUMMARY

[05] The present disclosure generally relates to compositions useful in the delivery of anionic therapeutic agents. More particularly, in some embodiments, the present disclosure relates to nanoscale, pH-responsive polycationic networks useful for the delivery of anionic biologic therapeutics and associated methods. The present disclosure provides, according to certain embodiments pH-responsive polycationic networks comprising siRNA in the polymer network. Such siRNA-containing networks may be useful for delivery of siRNA.

[06] In this disclosure, a robust synthesis approach to expand the range of therapeutics currently delivered via hydrogel technology is outlined. Through judicious materials selection and careful design of copolymer composition and molecular architecture, systems capable of responding to distinct physiological cues, with tunable physicochemical properties that are optimized to load, protect, and deliver valuable macromolecular payloads to their intended site of action may be engineered.

http://patentscope.wipo.int/search/en/detail.jsf?docId=WO2014059430