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ARTIFICIAL beta-CELLS AND METHODS OF USE THEREOF

A technology of granule and membrane fusion, applied in the field of treatment of diseases, can solve the problems of elusive replication and so on

Pending Publication Date: 2020-06-30
NORTH CAROLINA STATE UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although multi-compartmental assemblies have been created to recreate the hierarchical architecture of cells for the delivery of drug mixtures or cascade reactions (Boyer, C. et al., ACS Nano 1, 176-182 (2007); Wong, B. et al. , Adv.Mater.23, 2320-2325 (2011); Marguet, M. et al., Angew.Chem.Int.Ed.51, 1173-1176 (2012); Peters, R. et al., Angew.Chem.Int. .Ed.53, 146-150 (2014); Elani, Y. et al., Nat.Commun.5, 5305-5309 (2014); Chiu, H. et al., Angew.Chem.Int.Ed.47, 1875-1878 (2008)), but replication of native cellular 'sense-response' behavior remains elusive

Method used

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  • ARTIFICIAL beta-CELLS AND METHODS OF USE THEREOF
  • ARTIFICIAL beta-CELLS AND METHODS OF USE THEREOF
  • ARTIFICIAL beta-CELLS AND METHODS OF USE THEREOF

Examples

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example 1

[0135] Materials and general methods.

[0136] Material. All lipids, including egg phosphatidylcholine (EPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), dipalmitoylphosphatidylcholine (DPPC), 1,2- Dioleoyl-sn glycerol-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) (ammonium salt) and 1,2-dioleoyl-sn - Glycerol-3-Phosphatidylethanolamine - Lissamine - Rhodamine B, all purchased from Avanti Polar Lipids, Inc. All peptides were synthesized by Biochem Co., Ltd. (Shanghai, China). All DNA was purchased from DNA Technologies, Inc. (Coralville, IA, USA). Cholesterol, glucose oxidase, catalase, gramicidin A, methoxypolyethylene glycol maleimide (mPEG-Mal, molecular weight = 5000), phenylmethylsulfonyl fluoride (PMSF), Dialkyl β-D-maltoside (DDM) and 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) were purchased from Sigma-Aldrich. Human recombinant insulin was purchased from Life Technology. Anti-Glucose Transporter 2 antibody was purchased fr...

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Abstract

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.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Patent Application Serial No. 62 / 559,909 filed September 18, 2017, the disclosure of which is expressly incorporated herein by reference in its entirety. technical field [0003] The disclosure herein relates to granules, methods for delivering therapeutic agents, and methods for treating diseases such as diabetes. Background technique [0004] Pancreatic β cells dynamically regulate insulin secretion to maintain blood glucose homeostasis. Destruction or dysfunction of these cells leads to type 1 and type 2 diabetes, a family of chronic diseases that currently affect more than 415 million people in the world (Rorsman, P., Annu. Rev. Physiol. 75, 155-179( 2013); Yu, J. et al., Proc. Natl Acad. Sci. USA 112, 8260-8265 (2015); Ohkubo, Y. et al., Diabetes. Res. Clin. Pract. 28, 103-117 (1995)). Insufficient glycemic control due to loss of β-cell function can lead to...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/69A61K9/51A61K31/00A61K31/04A61K31/44
CPCA61K9/127A61K47/6911A61K38/28A61K47/42
Inventor 顾臻陈昭伟
Owner NORTH CAROLINA STATE UNIV
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