University of California

Huan Meng

Andre E Nel

Xiangsheng Liu

Jeffrey I Zink

Zongxi Li

Monty Liong

April D Pyle

Tian Xia

Min Xue

Melissa J Spencer

Courtney S Young

Ying Ji

Michael Reza Emami

Derrick Y Tarn

Sanaz Gardner

Kuo-Ching Mei

Zhaoxia Ji

In order to facilitate the approval and commercialization of silicasome drug delivery systems (e.g. irinotecan silicasomes) it is necessary to scale up synthesis of the drug-loaded silicasomes. In this regard, it was discovered that the synthesis protocols used for laboratory synthesis of drug-loaded silicasomes (e.g., 500 mg/batch) do not scale to large scale silicasome production, because the resulting products were too heterogeneous for use as pharmaceuticals. Accordingly, new methods are provided herein that effectively afford the large-scale production of mesoporous silica nanoparticles (MSNPs) and lipid bilayer coated MSNPs (silicasomes).

Scale up synthesis of silicasome nanocarriers

A nanocarrier including a silica body having a surface and defining a plurality of pores that are suitable to receive molecules therein is described. The nanocarrier also includes a lipid bilayer coating the surface, and a cargo-trapping agent within the phospholipid bilayer. The phospholipid bilayer stably seals the plurality of pores. The cargo-trapping reagent can be selected to interact with a desired cargo, such as a drug.

Mesoporous silica nanoparticles with lipid bilayer coating for cargo delivery

A submicron structure comprising a silica body defining a plurality of pores that are suitable to receive molecules therein, and having a surface, and a phospholipid bilayer coating the surface, wherein said submicron structure has a maximum dimension of less than one micron, and wherein the phospholipid bilayer stably seals the plurality of pores; and wherein the submicron structure is a member of a monodisperse population of submicron structures.

Lipid bilayer coated mesoporous silica nanoparticles with a high loading capacity for one or more anticancer agents

In various embodiments a polyrotaxane carrier for in vivo delivery of a nucleic acid is provided. In certain embodiments the carrier comprises: a multi-arm polyethylene glycol (PEG) backbone comprising at least three arms; at least one cyclic compound having a cavity, where an arm of said multi-arm PEG backbone is threaded into the cavity of said cyclic compound forming an inclusion complex; a bulky moiety capping the terminal of the arm(s) threaded into said cyclic compound where said moiety inhibits dethreading of the cyclodextrin from the arm(s) of said backbone; and where at least one arm of said PEG backbone is free of cyclic compounds; and where said carrier has a net positive charge.

Multi-armed polyrotaxane platform for protected nucleic acid delivery

In certain embodiments a platform technology for the facilitating immune therapy in the treatment of cancer is provided. In certain embodiments nanocarriers are provided that facilitate delivery of an IDO inhibitor in conjunction with an inducer of cell death (ICD-inducer). In certain embodiments the IDO inhibitor is conjugated to a component of a lipid bilayer forming a nanovesicle. In still another embodiment, methods and compositions are provided where an ICD-inducing agent (e.g., doxorubicin, oxaliplatin, mitoxantrone etc.) and an IDO pathway inhibitor (e.g., an IDO inhibitor-prodrug) are integrated into a nanocarrier (e.g. a lipid-bilayer (LB)-coated nanoparticle), that allows systemic delivery to orthotopic pancreatic cancer site.

Nano-enabled immunotherapy in cancer

Mesoporous silica nanoparticles with a lipid bilayer coating for cargo delivery

A submicron structure having a silica body defining a plurality of pores is described. The submicron body may be spherical or non-spherical, and may include a cationic polymer or co-polymer on the surface of said silica body. The submicron structure may further include an oligonucleotide and be used to deliver the oligonucleotide to a cell. The submicron structure may further include a therapeutic agent and be used to deliver the therapeutic agent to a cell. An oligonucleotide and therapeutic agent may be used together. For example, when the oligonucleotide is an siRNA, the composition may be used to decrease cellular resistance to the therapeutic agent by decreasing translation of a resistance gene.

Cationic polymer coated mesoporous silica nanoparticles and uses thereof

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Los Angeles, CA, United States of America

Huan Meng