Biocompatible crosslinked hydrogels, drug-loaded hydrogels and methods of using the same

A composition comprising a biocompatible hydrogel and an analgesic, wherein the analgesic is uniformly distributed in the hydrogel as in situ generated particles, and wherein the biocompatible hydrogel is produced by a method comprising:

• mixing a first compound and a second compound to obtain a first mixture,
• adding an acidic aqueous solution and the analgesic to the first mixture to obtain a first solution,
• adding a basic aqueous solution to the first solution, wherein,
• the first compound is a compound of Formula I:
• wherein
• each R1 is independently selected from the group consisting of hydrogen, alkyl, —C(═O)R3, and —C(═O)OR3;
• each R2 is independently selected from the group consisting hydrogen, alkyl, and —(CH2CH2O)n—R4,
• R3 is selected from the group consisting of hydrogen, halogen, amino, monoalkylamino, dialkylamino, alkyl, carbocyclyl, and heterocyclyl;
• each R4 is independently selected from the group consisting hydrogen, alkyl, —CH2CH2OH, and —CH2CH2OR1;
• each n is independently an integer greater than 1;
• wherein at least one of R1 is not hydrogen or alkyl;
• and
• the second compound is a compound of Formula III:
• wherein
• each R5 is independently selected from the group consisting of hydrogen, alkyl, —OR7, —SR7, and —N(R7)2;
• each R6 is independently selected from the group consisting hydrogen, alkyl, and —(CH2CH2O)n—R8;
• each R7 is independently selected from the group consisting of hydrogen, alkyl, carbocyclyl, and heterocyclyl;
• each R8 is independently selected from the group consisting hydrogen, alkyl, and —CH2CH2R5;
• each n is independently an integer greater than 1;
• wherein at least one of —R5 is not hydrogen or alkyl, and
• wherein the analgesic is a local anesthetic selected from the group consisting of bupivacaine, levobupivacaine, ropivacaine, lidocaine, mepivacaine, prilocaine, cinchocaine, etidocaine, articaine and salts thereof.