Single coated paperboard

Abstract

The present invention provides methods, systems, and compositions for ARMM-mediated delivery of molecules of interest (e.g., therapeutic agents) to cells and tissues of the eye. The present invention further relates to compositions and methods of producing, testing, and administering ARRDC1-mediated microvesicles (“ARMMs”) to internal structures of the eye. More particularly, the present invention provides compositions and methods of producing, testing, and administering ARMMs particles comprising one or more therapeutic agents (e.g., biological molecules including, but not limited to, CRISPR/Cas9 and other similar endonucleases, base editors, small molecules, proteins, and nucleic acids (e.g., DNA, RNA, siRNA, mRNA, miRNA, and the like)). Also provided are methods of administering therapeutic agents associated with ARMMs, including, but not limited to, methods of treating or contacting cells and tissues of the eye in one or more dosing regimens. In particular, the present invention provides methods of administering therapeutic agents via ARMMs to the cells and tissues that comprise the retina or into the subretinal space. Additionally, the present invention relates to methods of manufacturing (e.g., culturing, clarifying, separating, and concentrating) the inventive compositions from stable producer cell lines and from cell cultures.

1 . A coated paperboard comprising a paperboard substrate and a coating layer applied directly to a surface of a first side of the paperboard substrate, wherein:
 the coating layer comprises a polymeric binder and a calcium carbonate pigment in a dry weight ratio between 10:100 and 17:100;   the polymeric binder and the calcium carbonate pigment amount to at least 85% of the dry weight of the coating layer;   the particle size distribution (%<2 μm) of said calcium carbonate pigment is between 50 and 70; and   the coating layer is the only pigment-based coating applied to the first side of the coated paperboard.   
     
     
         2 . The coated paperboard of  claim 1 , wherein the coating layer is applied by dispersion coating and is the only coating layer applied to the first side of the coated paperboard by dispersion coating. 
     
     
         3 . The coated paperboard of  any one of previous claims , wherein the polymeric binder is a styrene-based copolymer. 
     
     
         4 . The coated paperboard of  claim 3 , wherein the styrene-based copolymer is a styrene-butadiene copolymer or a styrene-acrylate copolymer. 
     
     
         5 . The coated paperboard of  any one of previous claims , wherein the calcium carbonate pigment is ground calcium carbonate. 
     
     
         6 . The coated paperboard of  any one of the previous claims , wherein the coat weight of the coating layer is at least 10 g/m 2 , preferably at least 12 g/m 2 . 
     
     
         7 . The coated paperboard of  claim 6 , wherein the coat weight of the coating layer is 10-20 g/m 2 , such as 10-18 g/m 2 . 
     
     
         8 . The coated paperboard of  claim 6 , wherein the coat weight of the coating layer is 12-20 g/m 2 , such as 12-18 g/m 2 , such as 12-16 g/m 2 . 
     
     
         9 . The coated paperboard of  any one of previous claims , which is a liquid packaging board (LPB). 
     
     
         10 . The coated paperboard of  claim 9 , wherein the paperboard substrate comprises at least two, such as at least three, layers and each layer comprises hydrophobic size. 
     
     
         11 . The coated paperboard of  claim 10 , wherein each layer of the paperboard substrate comprises at least 1.5 kg/tonne fibre of hydrophobic size. 
     
     
         12 . The coated paperboard of  claim 11 , wherein the hydrophobic size is ASA, AKD and/or rosin size.