Drug release from pH‐responsive thermogelling pentablock copolymers

Abstract

A novel pH-dependent injectable sustained delivery system was developed by utilizing a cationic pentablock copolymer that exhibits a thermoreversible sol-gel transition. Aqueous solutions of the pentablock copolymer, consisting of poly(2-diethylaminoethyl-methyl methacrylate)-poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)-poly(2-diethylaminoethyl-methyl methacrylate) (PDEAEM(25)-PEO(100)-PPO(65)-PEO(100)-PDEAEM(25)) exhibit temperature and pH dependent micellization due to the lower critical solution temperature of the PPO blocks and the polyelectrolyte character of the PDEAEM blocks, respectively. Aqueous solutions of the copolymers above 12 wt % are free flowing liquids at room temperature and form elastic physical hydrogels reversibly above 37 degrees C. Hydrophobic probe absorbance studies indicate that pentablock copolymer micelles increase the solubility of sparingly soluble drugs. Solutions of the pentablock copolymer that form gels at body temperature exhibit sustained zero-order release in in vitro experiments. The release rates of model drugs and proteins were significantly influenced by the pH of the release media, thereby making these polymers ideal candidates for modulated drug delivery.

Synthesis and Characterization of Ionic Block Copolymer Templated Calcium Phosphate Nanocomposites

“…These micelles entangle to form viscous gels at higher temperatures or concentrations, typically above 25 uC. 9 The temperaturedependent phase transformation of the copolymers allows mixing of the solutions of copolymer and inorganic constituents followed by formation of a homogeneous mixture of the micelle spheres and calcium phosphate by manipulating the temperature and/or pH of the solution. While previous studies were limited to calcium phosphate-polymer interaction on the surface of a bulk polymer, or agglomerates of nanocomposites at the sub-micro scale from solution, these polymers make it possible to precipitate calcium phosphate in the interstitial spaces between and on the surfaces of the concentrated spherical micelles within a macro-scale copolymer gel formed completely by self-assembly.…”

Nanostructures and Nanostructured Networks for Smart Drug Delivery

“…Temperature-and pH-dependent micellization was demonstrated for the pentablock copolymer, consisting of poly(2-diethylaminoethyl-methyl methacrylate)-poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)-poly(2-diethylaminoethyl-methyl methacrylate) (PDEAEM25-PEO100-PPO65-PEO100-PDEAEM25) [169]. Such responsiveness enables the preparation of in situ gelling solutions that, once at body temperature, can regulate drug release precisely as a function of small changes in pH.…”

Drug release characteristics of modified PHEMA hydrogel containing thermo-responsive pluronic copolymer

“…1 Among the different types of hydrogels, stimuli-responsive polymers and hydrogels, which undergo a phase transition in response to external stimuli like temperature, 2-6 pH, 7,8 and light, 9 have received much attention during the last several years. In particular, temperature-responsive hydrogels like poly(N-isopropylacrylacrylamide) (PNIPAAm) or poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic ® ) have been widely studied for use in diverse applications such as drug delivery, 10,11 tissue engineering, 12 and cell culture.…”