SOLUBLE HYDROPHOBIC CORE CARRIER COMPOSITIONS FOR DELIVERY OF THERAPEUTIC AGENTS, METHODS OF MAKING AND USING THE SAME

摘要

The present invention relates to a soluble hydrophobic-core carrier composition comprising (i) a linear polymeric backbone; (ii) a plurality of hydrophilic polymeric protective chains covalently linked and pendant to the polymeric backbone and (iii) at least one hydrophobic moiety covalently linked and pendant to the polymeric backbone. In certain embodiments, the weight ratio of hydrophilic protective chains to hydrophobic moieties in the carrier is at least 15:1. In other embodiments, at least 90% of the residues of the polymeric backbone are coupled to a hydrophilic polymeric protective chain or a hydrophobic moiety. In other embodiments, the composition further comprises (iv) a hydrophobic load molecule dissociably linked to the hydrophobic moiety of the carrier.

主权项

1. A method of making a soluble hydrophobic-core carrier, comprising:
step (a): contacting and reacting a carboxyl group or an alkyl carboxyl group of a hydrophilic polymeric protective chain with a carbodiimide reagent to provide a hydrophilic polymeric protective chain having an activated carboxyl group or an activated alkyl carboxyl group; step (b): mixing and reacting a plurality of the hydrophilic polymeric protective chain having the activated carboxyl group or the activated alkyl carboxyl group of step (a) and a polymer comprising a linear polymeric backbone comprising NH2-containing residues to provide a polymer comprising a linear polymeric backbone comprising a plurality of covalently-linked hydrophilic polymeric protective side chains and NH2-containing residues; step (c): contacting and reacting a hydrophobic molecule comprising a free carboxyl group with a carbodiimide reagent to provide a hydrophobic molecule comprising an activated carboxyl group; step (d): mixing and reacting the hydrophobic molecule comprising the activated carboxyl group of step (c) and the polymer comprising the linear polymeric backbone comprising a plurality of covalently-linked hydrophilic polymeric protective side chains and NH2-containing residues of step (b) to provide a hydrophobic-core carrier, wherein the hydrophobic-core carrier comprises
(i) a linear polymeric backbone;(ii) a plurality of hydrophilic polymeric protective side chains covalently linked and pendant to the linear polymeric backbone, wherein each hydrophilic polymeric protective side chain has a molecular weight between about 400 and about 20,000 Daltons; and(iii) at least one hydrophobic moiety covalently linked and pendant to the linear polymeric backbone; wherein the total weight ratio of the plurality of hydrophilic polymeric protective side chains and the hydrophobic moieties is in the range of 15:1 to 43:1 and wherein the hydrophobic-core carrier is soluble in water.