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Patent Issued for Functionalized Nanoceria Composition for Ophthalmic Treatment

August 19, 2014



By a News Reporter-Staff News Editor at Life Science Weekly -- University of Central Florida Research Foundation, Inc. (Orlando, FL) has been issued patent number 8795737, according to news reporting originating out of Alexandria, Virginia, by NewsRx editors (see also University of Central Florida Research Foundation, Inc.).

The patent's inventors are Seal, Sudipta (Oviedo, FL); Patil, Swanand D. (Orlando, FL); Haldar, Manas K. (Fargo, ND); Malik, Sanku (West Fargo, ND).

This patent was filed on December 21, 2012 and was published online on August 5, 2014.

From the background information supplied by the inventors, news correspondents obtained the following quote: "Countless individuals suffer from the ocular disease glaucoma. This condition describes a destruction of optic nerve cells and deterioration of eyesight as a result of increased intraocular pressure. The pressure is caused in part by a buildup of carbon dioxide in the eye. An enzyme that aids in the production of CO2 is human carbonic anhydrase II (hCAII). This Zn.sup.2+ containing metalloenzyme (FIG. 1) catalyzes the reversible hydration of carbon dioxide to bicarbonate and is commonly found in living organisms.

"Sulfonamide compounds have been shown to selectively inhibit hCAII even at low concentratons..sup.1 Therefore, inhibition of hCAII with sulfonamides constitutes one of the most physiological approaches for treatment of glaucoma. In 1958 Beasley et al. reported the in vitro binding of 4-carboxybenzene sulfonamide (CBS) to the carbonic anhydrase (CA) enzymes..sup.2 Since then, many other hCAII inhibitors based on this moiety have been reported..sup.3-5 A remarkable increase in the hCAII inhibition activity was observed for simple aliphatic esters of CBS..sup.5 Also, it is now extensively documented that significant enhancement of CA inhibition can be achieved through coupling the primary recognition aromatic sulfonamide motif with secondary binding elements..sup.3,5-9 The mechanism for inhibition of hCAII by CBS involves coordination of the sulfonamide group (as the anion) to the zinc atom in the active site of hCAII to form a complex in an exothermic reaction. 6, 10, 11.

"In ophthalmic diseases such as glaucoma, treatment with conventional liquid eye drops is an inefficient mode of therapy because of lachrymal drainage losses. Because of the high elimination rate, only a very small amount of about 1-3% of the dosage actually penetrates through the cornea and is able to reach intraocular tissues..sup.12-14 Nanoparticles provide a promising potential as drug carriers for ophthalmic applications. The colloidal nanoparticles may be applied in liquid form just like eye drop solutions. After optimal drug binding to the nanoparticles, the ocular bioavailability of many drugs is significantly enhanced in comparison to normal aqueous eye drop solutions..sup.12 Also, smaller particles improve patient comfort during administration as a scratchy feeling tends to occur with larger particles. Nanoparticles and microspheres of various synthetic polymers such as poly-butylcyanoacrylate,.sup.15,16 polylactic acid,.sup.17 polymethylmethacrylate,.sup.16 and so forth as well as natural biocompatible polymers like albumin.sup.18,19 have been used for ophthalmic drug delivery applications."

Supplementing the background information on this patent, NewsRx reporters also obtained the inventors' summary information for this patent: "With the foregoing in mind, in one embodiment, the present invention advantageously provides a composition comprising a plurality of nanoceria particles, a sufficient amount of at least one inhibitor of human carbonic anhydrase II associated with said plurality of nanoceria particles, and a pharmaceutically acceptable carrier containing said plurality of nanoceria particles with associated inhibitor. The at least one inhibitor of human carbonic anhydrase II preferably comprises 4-carboxybenzene sulfonamide. Preferably, the enzyme inhibitor is effective against human carbonic anhydrase II and the composition is used in treating an eye disease, particularly glaucoma, by contacting the eye with the composition.

"The composition may also further comprise a detectable tag associated with the plurality of nanoceria particles. The skilled will recognize that the term 'tag' indicates any atom or molecule which, when associated with the nanoceria, imparts a property which allows for tracking of the nanoceria during treatment. Tracking may be by any known method, for example, fluorescence responsive to ultraviolet light. In effect, the tag may be a fluorescent tag associated with said plurality of nanoceria particles and the fluorescent tag is preferably a fluorescein compound associated with said plurality of nanoceria particles, in particular, carboxyfluorescein.

"In this preferred embodiment of the invention, the nanoceria particles are made by a method comprising a reaction according to Scheme 1A, shown in FIG. 3. Moreover, the nanoceria particles associated with carboxyfluorescein are made by a method comprising a reaction according to Scheme 1B in FIG. 3.

"Another embodiment of the invention includes a composition comprising a plurality of nanoceria particles, a sufficient amount of at least one biologically active agent bound to said plurality of nanoceria particles, and a pharmaceutically acceptable carrier containing said plurality of nanoceria particles with bound inhibitor. Preferably, the biologically active agent comprises a medicinal drug and, particularly, an ophthalmically active drug, which could be an enzyme inhibitor. In particular, the biologically active agent could comprise a sulfonamide compound, especially one that inhibits human carbonic anhydrase.

"Another preferred embodiment of the invention includes a method of treating a patient's eye condition. The method comprises providing a composition containing a plurality of nanoceria particles associated with a drug and suspended in a pharmaceutically acceptable carrier, and contacting the patient's eye with the composition.

"In this embodiment, the drug preferably comprises an enzyme inhibitor and especially an inhibitor of human carbonic anhydrase. The eye condition comprises glaucoma and drug comprises 4-carboxybenzene sulfonamide. In the method, contacting the eye may be accomplished in any fashion known to the skilled but, typically would comprise a procedure selected from instilling, injecting, diffusing and combinations thereof.

"Nevertheless, while this disclosure preferably comprises nanoceria compositions and treatments directed to eye conditions and, particularly, to glaucoma, the invention includes within its scope the concept of associating a drug with the nanoceria particles as carriers. The range of drugs that can be employed in the invention is rather broad and includes any drug or pharmaceutical composition that can be complexed, associated with or otherwise bound to the nanoceria particles without significantly adversely affecting the biological activity of the drug."

For the URL and additional information on this patent, see: Seal, Sudipta; Patil, Swanand D.; Haldar, Manas K.; Malik, Sanku. Functionalized Nanoceria Composition for Ophthalmic Treatment. U.S. Patent Number 8795737, filed December 21, 2012, and published online on August 5, 2014. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=8795737.PN.&OS=PN/8795737RS=PN/8795737

Keywords for this news article include: Sulfones, Chemicals, Chemistry, Nanoparticle, Sulfonamides, Carbon Dioxide, Nanotechnology, Emerging Technologies, Enzymes and Coenzymes, University of Central Florida Research Foundation Inc.

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Source: Life Science Weekly


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