# US 10,117,942 B2 · Photoactivatable lipid-based nanoparticles as vehicles for dual agent delivery > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,117,942 B2 - Document ID: US10117942B2 - Status: Granted - Kind: B2 - Application number: 14/904,385 - Filed: 2014-07-09 - Published: 2016-05-19 - Granted: 2018-11-06 - Earliest claimed: 2013-07-12 - Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services; Baylor College of Medicine - Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Services; Baylor College of Medicine - Inventors: Anu Puri; Robert P. Blumenthal; Amit Joshi; Darayash B. Tata; Mathias Viard - Web page: https://patentgrep.com/patent/US10117942B2 ## CPC - A61K 47/546: {Porphyrines; Porphyrine with an expanded ring system, e.g. texaphyrine} - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) - A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} - A61K 41/0042: {Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion} - A61K 41/0071: {PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines} - A61K 47/6911: {the form being a liposome} - A61N 5/062: {Photodynamic therapy, i.e. excitation of an agent} - A61P 35/00: Antineoplastic agents - A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides} - A61N 5/067: using laser light - A61N 2005/0663: {Coloured light} - 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) - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Embodiments of photoactivatable, lipid-based nanoparticles are disclosed, as well as methods of making and using the nanoparticles. Pharmaceutical compositions including the nanoparticles also are disclosed. The lipid-based nanoparticles include a vesicle wall surrounding a cavity, wherein the vesicle wall includes (i) a lipid bilayer comprising 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC), dipalmitoylphosphatidylcholine (DPPC), and (ii) 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) within the lipid bilayer. The nanoparticles may further include an agent within the cavity. ## Claims ### Claim 1 A photoactivatable lipid-based nanoparticle, comprising: a vesicle wall surrounding a cavity, the vesicle wall comprising (i) a lipid bilayer comprising (a) from 10 mol % to 20 mol % 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC), (b) from 3 mol % to 5 mol % 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol) (DSPE-PEG), and (c) dipalmitoylphosphatidylcholine (DPPC), and (ii) 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) within the lipid bilayer, wherein the vesicle wall has a lipid:HPPH weight ratio from 80:1 to 10:1, and wherein the lipid bilayer is destabilized by targeted application of light having a wavelength of 650-670 nm and a selected intensity for an effective period of time. ### Claim 2 (depends on 1) The photoactivatable lipid-based nanoparticle of claim 1, wherein the lipid bilayer comprises one or more segregated regions of DC8,9PC and the HPPH is preferentially located within the one or more segregated regions of DC8,9PC. ### Claim 3 (depends on 1) The photoactivatable lipid-based nanoparticle of claim 1, wherein the nanoparticle has a diameter from 80 nm to 200 nm. ### Claim 4 (depends on 1) The photoactivatable lipid-based nanoparticle of claim 1, further comprising at least one agent within the cavity. ### Claim 5 (depends on 4) The photoactivatable lipid-based nanoparticle of claim 4, wherein the agent is an anti-cancer agent, an imaging agent, or an anti-inflammatory agent. ### Claim 6 (depends on 5) The photoactivatable lipid-based nanoparticle of claim 5, wherein the agent is an anti-cancer agent. ### Claim 7 (depends on 6) The photoactivatable lipid-based nanoparticle of claim 6, wherein the agent is topotecan. ### Claim 8 (depends on 1) A pharmaceutical composition comprising a photoactivatable lipid-based nanoparticle according to claim 1 and a pharmaceutically acceptable carrier. ### Claim 9 (depends on 1) The method of claim 1, wherein the lipid bilayer comprises 76-86 mol % DPPC. ### Claim 10 (depends on 4) A method for delivering an agent from a photoactivatable lipid-based nanoparticle, the method comprising: providing a photoactivatable lipid-based nanoparticle according to claim 4; and subsequently irradiating the photoactivatable lipid-based nanoparticle with targeted application of light having a wavelength of 650-670 nm and a selected intensity for an effective period of time to activate at least a portion of the HPPH and release at least a portion of the agent from the cavity of the photoactivatable lipid-based nanoparticle. ### Claim 11 (depends on 10) The method of claim 10, wherein irradiating the photoactivatable lipid-based nanoparticle with targeted application of light comprises irradiating the photoactivatable lipid-based nanoparticle with a laser that produces the light having a wavelength of 650-670 nm. ### Claim 12 (depends on 10) The method of claim 10, wherein: (a) the selected intensity is from 1 mW to 500 mW; (b) the effective period of time is at least 30 seconds; or (c) both (a) and (b). ### Claim 13 (depends on 10) The method of claim 10, wherein the agent is a bioactive agent, the method further comprising: identifying a subject as having a condition that may be treated with HPPH, the bioactive agent, or both HPPH and the bioactive agent; administering the photoactivatable lipid-based nanoparticle to the subject; and subsequently irradiating the photoactivatable lipid-based nanoparticle by targeted application of light having a wavelength of 650-670 nm and a selected intensity to a targeted portion of the subject for the effective period of time. ### Claim 14 (depends on 13) The method of claim 13, wherein the subject has a tumor and the targeted portion of the subject includes an area proximate a location of the tumor. ### Claim 15 (depends on 14) The method of claim 14, wherein administering the photoactivatable lipid-based nanoparticle to the subject comprises administering an amount of the photoactivatable lipid-based nanoparticle effective to induce tumor size regression. ### Claim 16 (depends on 13) The method of claim 13, wherein irradiating is performed 4-6 hours after administering the photoactivatable lipid-based nanoparticle to the subject. ### Claim 17 (depends on 13) The method of claim 13, wherein administering the photoactivatable lipid-based nanoparticle to the subject comprises intravenously injecting the photoactivatable lipid-based nanoparticle into the subject. ### Claim 18 (depends on 13) The method of claim 13, wherein administering the photoactivatable lipid-based nanoparticle to the subject comprises administering a pharmaceutical composition comprising the photoactivatable lipid-based nanoparticle to the subject. ### Claim 19 (depends on 13) The method of claim 13, wherein subsequently irradiating the photoactivatable lipid-based nanoparticle by targeted application of light comprises: externally applying the light to the targeted portion of the subject for the effective period of time, thereby transcutaneously applying the light to the tumor; or internally applying the light to the targeted portion of the subject for the effective period of time. ### Claim 20 (depends on 13) The method of claim 13, wherein the bioactive agent is an anti-cancer agent. ### Claim 21 (depends on 20) The method of claim 20, wherein the anti-cancer agent is topotecan.