Biodegradable low molecular weight triblock poly (lactide-co-glycolide) polyethylene glycol copolymers having reverse thermal gelation properties

An aqueous biodegradable polymeric drug delivery composition possessing reverse thermal gelation properties comprised of an aqueous phase having uniformly contained therein:

• (a) an effective amount of a drug;
• and
• (b) a biodegradable ABA- or BAB-type triblock polymer said ABA triblock having the formula:
• PL(G).sub.z-1 A-PEG-PL(G).sub.z-1 A
• and said BAB triblock having the formula:
• PEG-PL(G).sub.z-1 A-PEG
• wherein z is an integer of 1 or 2, wherein the A block is represented by PL(G).sub.z-1 A such that when z is 2 the A block is a poly(lactide-co-glycolide) or PGLA copolymer, and when z is 1 the A block is a poly(lactide) or PLA polymer and wherein the B block is represented by PEG which is a hydrophilic polyethylene glycol polymer, said triblock polymer having a weight average molecular weight of between about 2000 to 4990, and wherein, in the triblock polymer, the PL(G).sub.z-1 A A-block comprises about 51 to 83% by weight of said polymer and the PEG B-block comprises about 17 to 49% by weight of said polymer.

A method for the administration of a drug to a warm blooded animal in a controlled release form which comprises:

• (1) providing an aqueous biodegradable polymeric drug delivery composition possessing reverse thermal gelation properties comprised of an aqueous phase having uniformly contained therein:
• (a) an effective amount of a drug;
• and
• (b) a biodegradable ABA- or BAB-type triblock polymer said ABA triblock having the formula:
• PL(G).sub.z-1 A-PEG-PL(G).sub.z-1 A
• and said BAB triblock having the formula:
• PEG-PL(G).sub.z-1 A-PEG
• wherein z is an integer of 1 or 2, wherein the A block is represented by PL(G).sub.z-1 A such that when z is 2 the A block is a poly(lactide-co-glycolide) or PLGA copolymer and when z is 1 the A block is a poly(lactide) or PLA polymer and wherein the B block is represented by PEG which is a hydrophilic polyethylene glycol polymer, said block copolymer having a weight average molecular weight of between about 2000 to 4990, and wherein, in the triblock polymer, the PL(G).sub.z-1 A A-block comprises about 51 to 83% by weight of said polymer and the PEG B-block comprises about 17 to 49% by weight of said polymer,
• (2) maintaining said composition as a liquid at a temperature below the gelation temperature of said triblock polymer;
• and
• (3) administering said composition as a liquid to said warm blooded animal with the subsequent formation of a gel as the temperature of said composition is raised by the body temperature of said animal to be above the gelation temperature of said triblock polymer.

A method for enhancing the solubility of a drug comprising uniformly admixing an effective amount of said drug in an aqueous biodegradable polymeric drug delivery composition possessing reverse thermal gelation properties said aqueous composition being comprised of an aqueous phase having uniformly contained therein a biodegradable ABA- or BAB-type triblock polymer said ABA triblock having the formula:

• PL(G).sub.z-1 A-PEG-PL(G).sub.z-1 A
• and said BAB triblock having the formula:
• PEG-PL(G).sub.z-1 A-PEG
• wherein z is an integer of 1 or 2, wherein the A-block is represented by PL(G).sub.z-1 A such that when z is 2 the A-block is a poly(lactide-co-glycolide) or PLGA copolymer, and when z is 1 the A-block is a poly(lactide) or PLA polymer and wherein the B-block is represented by PEG which is a hydrophilic polyethylene glycol polymer, said triblock polymer having a weight average molecular weight of between about 2000 to 4990, and wherein, in the tri-block polymer, the PL(G).sub.z-1 A A-block comprises about 51 to 83% by weight of said polymer and the PEG B-block comprises about 17 to 49% by weight of said polymer.

A method for enhancing the stability of a drug comprising uniformly admixing an effective amount of said drug in an aqueous biodegradable polymeric drug delivery composition possessing reverse thermal gelation properties said aqueous composition being comprised of an aqueous phase having uniformly contained therein a biodegradable ABA- or BAB-type triblock polymer said ABA triblock having the formula:

• PL(G).sub.z-1 A-PEG-PL(G).sub.z-1 A
• and said BAB triblock having the formula:
• PEG-PL(G).sub.z-1 A-PEG
• wherein z is an integer of 1 or 2, wherein the A-block is represented by PL(G).sub.z-1 A such that when z is 2 the A-block is a poly(lactide-co-glycolide) or PLGA copolymer, and when z is 1 the A-block is a poly(lactide) or PLA polymer and wherein the B-block is represented by PEG which is a hydrophilic polyethylene glycol polymer, said triblock polymer having a weight average molecular weight of between about 2000 to 4990, and wherein, in the triblock Polymer, the PL(G).sub.z-1 A A-block comprises about 51 to 83% by weight of said polymer and the PEG B-block comprises about 17 to 49% by weight of said polymer.