# US 10,117,886 B2 · Hyaluronidase and a low density second PEG layer on the surface of therapeutic-encapsulated nanoparticles to enhance nanoparticle diffusion and circulation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,117,886 B2 - Document ID: US10117886B2 - Status: Granted - Kind: B2 - Application number: 14/726,770 - Filed: 2015-06-01 - Published: 2015-12-03 - Granted: 2018-11-06 - Earliest claimed: 2014-05-30 - Applicants: Hao Cheng; Hao Zhou - Inventors: Hao Cheng; Hao Zhou - Web page: https://patentgrep.com/patent/US10117886B2 ## CPC - A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} - A61K 9/5153: {Polyesters, e.g. poly(lactide-co-glycolide)} - A61K 47/6911: {the form being a liposome} - Y10T 428/2982: Particulate matter [e.g., sphere, flake, etc.] - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## Abstract A delivery system comprising an organic nanoparticle, a hyaluronidase anchored or conjugated to the organic nanoparticle. The organic nanoparticle may be selected from a polymer-based nanoparticle, a lipid-based nanoparticle and nanoparticle formed by lipid-like molecules. In some embodiments, the hyaluronidase is covalently bound to a linker or spacer which, in turn, is anchored or covalently bound to the organic nanoparticle. The delivery system may also comprise an active pharmaceutical agent, a diagnostic agent, and/or a cellular membrane. The organic nanoparticle may further have a low density poly(ethylene glycol) layer on the surface. Methods for using the delivery system including for treating or diagnosing a disease are also provided. The organic nanoparticle provides enhanced diffusion/penetration through the extracellular matrix found in tumors, as well as increased circulation time in a human or animal body. ## Claims ### Claim 1 A delivery system, comprising: an organic nanoparticle; and a hyaluronidase anchored or conjugated to the organic nanoparticle. ### Claim 2 (depends on 1) The delivery system of claim 1, wherein the organic nanoparticle is selected from a polymer-based nanoparticle, a lipid-based nanoparticle and a nanoparticle formed by lipid-like molecules. ### Claim 3 (depends on 1) The delivery system of claim 1, wherein the hyaluronidase is anchored or conjugated to the organic nanoparticle via a linker or spacer. ### Claim 4 (depends on 1) The delivery system of claim 1, wherein the organic nanoparticle has a diameter of from about 10 to about 500 nm, or from about 20 to about 400 nm, or from about 40 to about 300 nm, or from about 60 to about 250 nm. ### Claim 5 (depends on 2) The delivery system of claim 2, wherein the organic nanoparticle is a polymer-based nanoparticle that comprises one or more biodegradable polymers. ### Claim 6 (depends on 5) The delivery system of claim 5, wherein the one or more biodegradable polymers are selected from polyesters, polyhydroxybutyric acids, polyhydroxyvaleric acids, polycaprolactones, polyesteramides, polycyanoacrylates, poly(amino acids), polycarbonates, polyanhydrides, and combinations thereof. ### Claim 7 (depends on 5) The delivery system of claim 5, wherein the biodegradable polymers are selected from polylactic acid (polylactide), polylactide-polyglycolide, polyglycolide, poly(lactide-co-glycolide), polyethylene glycol-co-lactide and combinations thereof. ### Claim 8 (depends on 1) The delivery system of claim 1, wherein the organic nanoparticle is a liposome and the liposome has an aqueous inner core. ### Claim 9 (depends on 3) The delivery system of claim 3, wherein the linker or spacer is anchored or conjugated to the organic nanoparticle and covalently bound to the hyaluronidase. ### Claim 10 (depends on 9) The delivery system of claim 9, wherein the linker or spacer is a linker with two reactive groups capable of forming covalent bonds. ### Claim 11 (depends on 9) The delivery system of claim 9, wherein the linker or spacer is a spacer with one reactive group capable of forming a covalent bond. ### Claim 12 (depends on 9) The delivery system of claim 9, wherein the linker or spacer comprises a polyamino acid chain. ### Claim 13 (depends on 9) The delivery system of claim 9, wherein the linker or spacer comprises a maleimide group, an N-hydroxysuccinimide ester group, a sulfo-N-hydroxysuccinimide ester group, or an imidoester group. ### Claim 14 (depends on 1) The delivery system of claim 1, further comprising an active pham1 aceutical agent encapsulated in the organic nanoparticle, or conjugated or anchored to an outer surface of the organic nanoparticle. ### Claim 15 (depends on 14) The delivery system of claim 14, wherein the active pharmaceutical agent is an anti-cancer drug selected from alkylating agents, antimetabolites, antigens, and radiosensitizers. ### Claim 16 (depends on 14) The delivery system of claim 14, wherein the active pharmaceutical agent is a cytotoxic agent. ### Claim 17 (depends on 16) The delivery system of claim 16, wherein the cytotoxic agent is selected from docetaxel, paclitaxel and paclitaxel palmitate. ### Claim 18 (depends on 1) The delivery system of claim 1, further comprising a diagnostic agent encapsulated in the organic nanoparticle, or conjugated or anchored on an outer surface of the organic nanoparticle. ### Claim 19 (depends on 18) The delivery system of claim 18, wherein the diagnostic agent is selected from a radiolabelled compound, fluorescently labeled compound, enzymatically labeled compound, magnetic compound . ### Claim 20 (depends on 1) The delivery system of claim 1, further comprising an antigen encapsulated in the organic nanoparticle. ### Claim 21 (depends on 1) The delivery system of claim 1, wherein the organic nanoparticle comprises a lipid-based membrane on an outer surface thereof, and the linker or spacer is anchored or conjugated to the lipid-based membrane. ### Claim 22 (depends on 21) The delivery system of claim 21, wherein the lipid-based membrane is selected from plasm a membrane isolated from a live cell, membrane of cellular organelle isolated from a live cell, and viral membrane. ### Claim 23 (depends on 21) The delivery system of claim 21, wherein the lipid-based membrane is isolated from a blood cell selected from red blood cell, white blood cell and platelet. ### Claim 24 (depends on 1) The delivery system of claim 1, further comprising an antibody conjugated on surface of the organic nanoparticle, wherein the antibody specifically binds to a surface antigen on a target tissue for the delivery system. ### Claim 25 (depends on 1) The delivery system of claim 1, further comprising a polyethylene glycol polymer, a polysaccharide, a polyamino acid or a zwitterionic polymer anchored or conjugated on a same surface of the nanoparticle as the hyaluronidase.