This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins. These compositions are not subject to accelerated blood clearance and they have an improved toxicity profile in vivo.

The present invention provides a surfactant having a formula selected from the group consisting of: B((X).sub.x(CH.sub.2).sub.a-M.sub.n(VI), (A-(CH.sub.2)(X).sub.xB(X).sub.x(CH.sub.2).sub.a-A).sub.n (IV), (A-(CH.sub.2).sub.a(X).sub.xB).sub.n (V), and (B).sub.n(X).sub.x(CH.sub.2).sub.aA (VII), wherein A is a perfluoropolyether; a is a positive integer; X is either a covalent bond or a linking group; x is a positive integer; B is a polyalkylene oxide unit; n is a positive integer greater than 1 and, in compounds comprising more than one A, B, X, a and x, each may be the same or different. The present invention also relates to methods of making such surfactants, uses of such surfactants and emulsions comprising such surfactants.

Provided herein are water-soluble prodrugs, compositions comprising such prodrugs, and related methods of making and administering the same. The prodrugs of the invention comprise a water-soluble polymer having three or more arms, at least three of which are typically covalently attached to an active agent, e.g., a small molecule. The conjugates of the invention provide an optimal balance of polymer size and structure for achieving improved drug loading, since the conjugates of the invention possess three or more active agents releasably attached to a multi-armed water-soluble polymer. The prodrugs of the invention are therapeutically effective, and exhibit improved properties in-vivo when compared to unmodified parent drug.

Methods and compositions are described for enhancing tissue regeneration or wound repair in a mammalian subject comprising a composition comprising (a) a proline hydroxylase inhibitor component or molecule that increases or upregulates HIF1a and (b) a carrier component comprising a hydrogel.

A fluorine-containing ether compound represented by Formula (1) is provided.

R.sup.1R.sup.2CH.sub.2R.sup.3CH.sub.2R.sup.4R.sup.5 (1)

(In Formula (1), R.sup.1 and R.sup.5 each represents a group having a heterocyclic ring and may be the same as or different from each other, R.sup.2 and R.sup.4 each represents a divalent linking group having a polar group and play be the same as or different from each other, and R.sup.3 represents a perfluoropolyether chain.)

An example of a bottlebrush polymer has a polymer backbone and a plurality of individual brush moieties bonded to the polymer backbone. The individual brush moieties include a ketone, a hydrophilic segment, and a surface adhesive terminal group. The brush moieties can be functionalized and/or cross-linked.

Provided herein are water-soluble prodrugs, compositions comprising such prodrugs, and related methods of making and administering the same. The prodrugs of the invention comprise a water-soluble polymer having three or more arms, at least three of which are typically covalently attached to an active agent, e.g., a small molecule. The conjugates of the invention provide an optimal balance of polymer size and structure for achieving improved drug loading, since the conjugates of the invention possess three or more active agents releasably attached to a multi-armed water-soluble polymer. The prodrugs of the invention are therapeutically effective, and exhibit improved properties in-vivo when compared to unmodified parent drug.

Micro-nano materials, products obtained by covalently modifying the surfaces of micro/nano materials with hydrophilic materials, and methods for making the same. The micro/nano materials on the surfaces have carboxyl groups or/and pro-carboxyl groups which are converted into their active esters. The products are covalently modified by forming amide bonds between the active esters on the surfaces and the modification agents; where the modification agents are hydrophilic compounds and/or hydrophilic polymers bearing primary and/or secondary aliphatic amines. Monomers bearing carboxyl groups and/or pro-carboxyl groups are used to produce an adequate number of carboxyl groups and/or pro-carboxyl groups on the surface of a polymer material to be modified. The carboxyl groups and/or pro-carboxyl groups are converted into active esters. A reasonably-sized modification agent bearing primary and/or secondary amines, zwitterions and hydrophilic linear spacer arms is used to form amide bonds and obtain a covalently modified surface layer.

The present invention provides nanocarriers for delivering polynucleotide sequences to cells, specifically immune cells, including dendritic cells and methods of use. The methods provide improved delivery and reduced toxicity over prior methods. The method of the present disclosure provide a system for delivering nucleic acids to a cell, consisting of a synthetic PEG-b-PPS-linker-DP polymer for producing nanostructures comprising a poly(ethylene glycol)-blockpoly (propylene sulfide) copolymer (PEG-b-PPS) conjugated with a dendritic-specific branched cationic peptide (DP). The system provides a non-toxic in-vitro method of delivering a polynucleotide to immune cells, including dendritic cells, comprising of contacting the cell in cell culture medium with a nanocarrier wherein the method is non-toxic to the cells. The methods described in the invention can be used for treating a subject in need of gene therapy, comprising administering to the subject an effective amount of the system comprising of a polynucleotide, wherein the polynucleotide contains a gen of interest for gene therapy.

Interleukin-15 muteins and other interleukin-15-related molecules are described, as well as methods of identifying interleukin-15 muteins and other interleukin-15-related molecules. Also described herein are modifications of the foregoing, which modifications may enhance a property (e.g., half-life) of the muteins or other molecules compared to human interleukin-15. Pharmaceutical compositions and methods of use are also described herein.