Photoactivatable lipid-based nanoparticles as vehicles for dual agent delivery
Inventors
Puri, Anu • Blumenthal, Robert P. • Joshi, Amit • Tata, Darayash B. • Viard, Mathias
Assignees
Baylor College of Medicine • US Department of Health and Human Services
Publication Number
US-10117942-B2
Publication Date
2018-11-06
Expiration Date
2034-07-09
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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.
Core Innovation
The invention relates to photoactivatable, lipid-based nanoparticles, specifically liposomes, that include a vesicle wall surrounding a cavity. The vesicle wall comprises a lipid bilayer formed of 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC), dipalmitoylphosphatidylcholine (DPPC), and 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), a tetrapyrollic photosensitizer. The nanoparticles may encapsulate an agent within the cavity. Upon irradiation with near-infrared light (650-670 nm), the HPPH is activated, which destabilizes the lipid bilayer and triggers release of the encapsulated agent, enabling dual agent delivery.
The problem addressed by the invention is the need for liposomes that allow precise spatial and temporal control of therapeutic agent release at target sites, particularly for cancer therapy. Previous photo-triggerable liposomes commonly require ultraviolet light for activation, which is unsuitable for in vivo applications due to poor tissue penetration. There is a lack of liposomes responsive to wavelengths capable of penetrating tissue effectively to allow on-demand drug release in vivo.
The disclosed liposomes incorporate DC8,9PC and DPPC to form segregated lipid pockets within the lipid bilayer, with HPPH preferentially localizing within the DC8,9PC regions. This preferential location is believed to facilitate lipid bilayer destabilization upon near-infrared light photoactivation of HPPH, resulting in controlled release of an agent from the liposomal cavity. Additionally, the liposomes may include a stabilizing lipid such as DSPE-PEG to improve in vivo stability and circulation time. Methods of manufacturing, pharmaceutical compositions, and methods of using these liposomes for targeted delivery and treatment, especially cancer therapy, are also disclosed.
Claims Coverage
The patent contains 3 independent claims focusing on the nanoparticle composition, pharmaceutical composition, and methods of using and activating the nanoparticle.
Photoactivatable lipid-based nanoparticle composition
A lipid-based nanoparticle comprising a vesicle wall with a lipid bilayer including 10-20 mol % DC8,9PC, 3-5 mol % DSPE-PEG, DPPC, and HPPH located within the lipid bilayer.
Pharmaceutical composition containing the photoactivatable nanoparticle
A pharmaceutical composition comprising the photoactivatable lipid-based nanoparticle and a pharmaceutically acceptable carrier.
Method for delivering an agent using photoactivation
Providing a photoactivatable lipid-based nanoparticle containing an agent within its cavity and irradiating it with targeted light of 650-670 nm wavelength and selected intensity (1-500 mW) for an effective period (at least 30 seconds) to activate HPPH and release the agent.
The claims cover the composition of the photoactivatable lipid-based nanoparticle with defined lipid and photosensitizer constituents, pharmaceutical formulations containing the nanoparticle, and methods of targeted near-infrared light activation for controlled agent release and therapeutic use.
Stated Advantages
Allows precise spatial and temporal control of therapeutic agent release at target sites using near-infrared light activation suitable for in vivo applications.
Dual delivery of activated HPPH and an encapsulated agent provides combination chemotherapy at the tumor site.
Near-infrared light penetrates tissue more effectively than ultraviolet light, enabling non-invasive or minimally invasive treatment.
PEGylation of liposomes increases blood circulation time and stability in vivo.
Photo-triggering does not destroy liposomes, allowing for gradual release and potential repeated activation.
Documented Applications
Targeted delivery and on-demand release of anti-cancer agents to tumor tissue in vivo.
Photodynamic therapy combining activated HPPH and chemotherapy for tumor shrinkage and growth inhibition.
Nano-imaging tools and diagnostics using encapsulated imaging agents.
Use as delivery vehicles for anti-inflammatory agents or nucleic acid molecules such as siRNA.
Potential for oral vaccines and biomimetic applications.
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