North Carolina State University

University of California

Columbia University

Zhen Gu

Yanqi Ye

Chao Wang

Jicheng Yu

Jinqiang Wang

Yunfeng Lu

Yi Tang

Ming Yan

Anuradha Biswas

Guoping Fan

Zhaowei Chen

Quanyin Hu

Li Qiang

Yuqi Zhang

Wanyi Tai

Guojun Chen

Ran Mo

Xiuli Hu

Tianyue Jiang

Hongjun Li

Zejun Wang

Qian Chen

Di Wen

Xudong Zhang

Disclosed herein is a particle containing an inner liposomal vesicle (ILV) encapsulating a therapeutic agent; an outer liposomal vesicle (OLV) encapsulating the ILV; a membrane fusion-promoting agent; and a pH-altering agent. Also disclosed are methods of delivering a therapeutic agent to a subject comprising: a) providing a herein disclosed particle b) triggering ILV and OLV fusion; and c) releasing the therapeutic agent outside of the OLV. Also disclosed are methods for treating a disease in a subject in need thereof comprising: administering to a subject a herein disclosed particle. Also disclosed are methods to release insulin to an environment comprising increased glucose levels, the method comprising exposing to the environment a herein disclosed particle.

Artificial beta cells and methods of use thereof

Disclosed are therapeutic agent delivery vehicle comprising a modified platelet comprising a therapeutic agent cargo and a targeting moiety and methods for treating cancer comprising administering the same to a subject.

Cell assembly-mediated delivery of checkpoint inhibitors for cancer immunotherapy

Disclosed are compositions and methods for microneedle patches comprising copolymer designed for glucose triggered insulin delivery. In one aspect, disclosed herein are microneedle patches comprising insulin loaded copolymers; wherein the insulin dissociates from the microneedle in an hyperglycemic environment; wherein the copolymer comprises poly(N-vinylpyrrolidone-co-2-N(dimethylamino)ethyl acrylate-co-3-(acrylamido)phenylboronic acid and methods of their use.

Microneedle-array patches with glucose-responsive matrix for closed-loop insulin delivery

Disclosed herein are methods of treating/inhibiting/reducing a non-immunogenic cancer in a subject or inducing blockade inhibitor susceptibility (such as, for example, PD-1/PDLI, CTLA-4/B7-1/2, and/or CD47/SIRPa inhibitor susceptibility) in a tumor in a subject with a cancer, said methods comprising administering to the subject a hydrogel matrix comprising a chemotherapeutic agent (including, but not limited to gemcitabine) and a blockade inhibitor (including, but not limited to a PD-1/PD-LI blockade inhibitor, such as, for example nivolumab, pembrolizumab, pidilizumab, atezolizumab, avelumab, durvalumab, and BMS-936559; a CTLA-4/B7-1/2 inhibitor such as, for example, Ipilimumab; and/or a CD47/SIRPa inhibitor such as, for example Hu5F9-G4, CVI, B6H12, 2D3, CC-90002, and TTI-621).

Compositions comprising chemotherapeutic agents and checkpoint inhibitors and methods of use

Disclosed herein are self-degradable microneedle devices for the controlled-release of an immunotherapeutic agent. Also disclosed are methods for treating a disease (for example, cancer) using a self-degradable microneedle patch for the sustained delivery of an immunotherapeutic agent (for example, a PD1 antibody).

Enhanced cancer immunotherapy by microneedle patch-assisted delivery

Disclosed herein is a glucose-responsive insulin delivery system based on the interaction between the glucose-modified insulin and glucose transporters (GLUTs) on erythrocytes (or red blood cells, RBCs). After being conjugated with glucose, insulin can efficiently bind to RBC membranes. The binding is reversible in the setting of hyperglycemia, resulting in fast release of insulin and subsequent drop of blood glucose (BG) level in vivo. In some embodiments, the delivery vehicle can include: 1) intravenously injectable polymeric nanoparticles (˜100 nm in diameter) coated with RBC membrane and loaded with glucose-modified insulin and/or 2) painless microneedle (MN) patches loaded with the complex of GLUT and glucose-modified insulin.

Glucose responsive insulin delivery compositions and methods

Embodiments of the present disclosure relate generally to photoimmunotherapy for treating cancer. More particularly, the present disclosure provides photo-responsive dermal applicators that use transdermal microneedle arrays to administer an immunogenic composition and a photo-sensitive biological pigment to a subject to treat and/or prevent cancer. Photo-responsive dermal applicators of the present disclosure provide the ability to target cancerous tumors in a manner that is safer and less invasive than conventional means.

Dermal applicator for use in cancer photoimmunotherapy

A composition comprising an insulin-polymer conjugate and an insulin aptamer-glucagon conjugate is described. Depending upon the amount of insulin in the environment surrounding the composition, the insulin aptamer of the insulin aptamer-glucagon conjugate can bind to insulin in the insulin-polymer conjugate to form a non-covalent conjugate. When the amount of insulin in the surrounding environment rises, the insulin aptamer-glucagon conjugate can be released. Thus, the composition can be used to deliver glucagon in an insulin responsive manner. The composition can be loaded into microneedles, for example, to prepare microneedle arrays for skin patches. Methods of delivering glucagon to a subject are also described.

Insulin-responsive glucagon delivery patch

Disclosed herein are compositions and methods for delivering adipose tissue browning agents and/or fat modulating agents.

Locally-induced adipose tissue browning by microneedle patch for obesity treatment

A composition comprising a glucose-responsive charge-switchable polymer is described. In the absence of glucose or under normoglycemic conditions, the positively charged polymer can be complexed with negatively charged therapeutic agents, such as insulin. Under hyperglycemic conditions, the positive charge of the polymer is reduced, and the polymer/therapeutic agent complex can disassemble, allowing the therapeutic agent to be released. Pharmaceutical compositions, nanoparticles, and microneedle arrays of the polymer and/or polymer/therapeutic agent complex and methods of treating diabetes are also described.

Charge-switchable polymeric depot for glucose-triggered insulin delivery with ultrafast response

Disclosed herein are microneedle devices, kits comprising the microneedle devices, and methods of using the microneedle devices. Specifically, disclosed is a device for transport of a material across a biological barrier of a subject comprising: a plurality of microneedles each having a base end and a tip, with at least one pathway disposed at or between the base end and the tip; a substrate to which the base ends of the microneedles are attached or integrated; and at least one reservoir which is in connection with the base ends of the microneedles array, wherein the reservoir comprises an agent delivery system, wherein the agent delivery system comprises an agent to be transported across the biological barrier, or a means for producing an agent to be transported across the biological barrier, and a means for detecting a physiological signal from the recipient.

Methods and compositions related to physiologically responsive microneedle delivery systems

Disclosed herein is a glucose-responsive insulin delivery system based on the interaction between the glucose-modified insulin and glucose transporters (GLUTs) on erythrocytes (or red blood cells, RBCs). After being conjugated with a competitive inhibitor of a glucose transporter, insulin can efficiently bind to RBC membranes. The binding is reversible in the setting of hyperglycemia, resulting in fast release of insulin and subsequent drop of blood glucose (BG) level in vivo.

Glucose transporter inhibitor-modified insulin for glucose-responsive insulin delivery

Disclosed are compositions and methods for microneedle patches comprising diblock copolymer micelles designed for pH cascade and HOtriggered insulin delivery.

Core-shell microneedle patch for HOand pH cascade-triggered insulin delivery

The present disclosure provides compositions and methods for targeted delivery of therapeutic agents. The present disclosure further provides methods for treating or preventing the metastasis or recurrence of a cancer using platelets loaded with a therapeutic agent (for example, an immunotherapeutic agent).

Platelet compositions and methods for the delivery of therapeutic agents

The present disclosure relates to microneedle devices and methods for treating a disease (for example, diabetes) using a degradable cross-linked gel for self-regulated delivery of a therapeutic agent (for example, insulin).

Growing community of inventors

Los Angeles, CA, United States of America

Zhen Gu