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 conjugates having a degradable linkage and polymeric reagents useful in preparing such conjugates. The conjugates as well as the polymeric reagents used to form the conjugates include at least one of each the following: an aromatic moiety comprising an ionizable hydrogen atom, a spacer moiety, and a water-soluble polymer. Methods of making polymeric reagents and conjugates, as well as methods for administering conjugates and compositions, are also provided.

The invention provides compound of the general formula: ##STR00001##
in which each X independently represents a polymer chain; n represents an integer greater than 1; Q represents a linker; Y represents an amide group; and Z represents either CH.(CH.sub.2L).sub.2 or C(CH.sub.2L)(CH.sub.2), in which each L independently represents a leaving group. The compounds are useful reagents for the conjugation of polymers to proteins, the resulting conjugates being novel and also forming part of the invention.

The invention is based on the recognition that known antimicrobial compounds, such as nisin or other lantibiotics, can be made to form a long lasting antimicrobial surface coating by linking the peptide with a block polymer, such as PLURONIC F108 or an end group activated polymer (EGAP) in a manner to form a flexible tether and/or entrap the peptide. The entrapped peptide provides antimicrobial action by early release from entrapment while the tethered peptide provides longer lasting antimicrobial protection. Antimicrobial gels and foams may be prepared using the antimicrobial peptide containing block copolymers.

The present invention relates to micelle drug carriers and methods of using the micelles to deliver drugs to target cells. The micelles are useful, for example, for carrying and targeting drugs for the treatment of cancer to cancer cells. As one example, the disclosure provides pegylated octadecyl lithocholate micelles that are labeled with a peptide ligand for colorectal neo-plasia and that carry the small molecule mTOR inhibitor rapamycin to colorectal cancer cells.

A polyether group-containing compound of the formula (I). In each of the compound of the formula (I), one or two R are represented by (Rf-X.sup.f1-PE-X.sup.f2).sub.?X.sup.1, and one or two R are represented by R.sup.Si. The symbols are as defined in the description. ##STR00001##

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 respectively include a crosslinked oxyamine moiety, a hydrophilic segment, and a surface adhesive terminal group.

The present invention provides conjugates having a degradable linkage and polymeric reagents useful in preparing such conjugates. The conjugates as well as the polymeric reagents used to form the conjugates include at least one of each the following: an aromatic moiety comprising an ionizable hydrogen atom, a spacer moiety, and a water-soluble polymer. Methods of making polymeric reagents and conjugates, as well as methods for administering conjugates and compositions, are also provided.

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 respectively including a ketone, a hydrophilic segment, and a surface adhesive terminal group. The brush moieties can be functionalized and/or cross-linked.

Processes of preparing defined monomer sequence polymers are disclosed, in which a backbone portion of the polymer is first prepared by performing one or more sequential monomeric coupling reactions with intervening membrane diafiltration purification/isolation steps, followed by a step of decorating the backbone portion with one or more side chains at predetermined positions along its length. The process represents an improvement on prior art techniques, which impose limitations on the size of the side chains that may be present. Defined monomer sequence polymers that are obtainable by the processes are also disclosed.