Synthesis and aqueous solution properties of functionalized and thermoresponsive poly(D,L‐lactide)/polyether block copolymers

Abstract

Tri‐ and pentablock amphiphilic copolymers containing hydrophobic poly(D,L‐lactide) block(s) and hydrophilic polyethers were synthesized in order to obtain new precursor architectures suitable for drug delivery systems. Polyglycidol‐6‐poly(ethylene oxide)‐b‐poly(D,L‐lactide) possess high hydroxyl functionality provided by the linear polyglycidol block. Thus very stable hydroxyl functionalized micelles in aqueous media were obtained. On the other hand poly(D,L‐lactide)‐b‐poly(ethylene oxide)‐b‐poly(propylene oxide)‐b‐poly(ethylene oxide)‐b‐poly(D,L‐lactide) form temperature sensitive aggregates. The copolymers obtained were analyzed by SEC and NMR, and their aqueous solution properties were followed by cloud point measurements and determination of critical micellization temperature. TEM was used for particles visualization.

Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelle

“…This was consistent with the data reported previously. [28][29][30][31] All the CMC values were low enough (0.52-1.8 × 10 −8 mol/L) to maintain thermodynamic stability of micelles after intravenous injection which induced severe dilution. 32,33 Physicochemical characterization of micelles…”

Biodegradable polymers suitable for tissue engineering and drug delivery systems

“…[98]. The core of the micelles is formed by hydrophobic polylactide block, while the hydrophilic shell is made of polyethylene oxide block with polyglycidol hydroxyl groups on the end that opens an attractive approach for attachment of drug-targeting agent [98,99].…”

“…lactic acid) [98,99], have drawn big attention regarding the capability of incorporating two different active substances or the possibility of surface functionalization for selective drug targeting processes. Polymer based micelles generally have spherical shape sized from 10 to 100 nm [100] and core -shell architecture where segments dissolved in a particular solvent form the outer shell stabilizing the inner hydrophobic core [101,102].…”

“…Polyglycidol-poly(ethylene oxide)-poly(DL-lactide) (PG-PEO-PL) triblock copolymers and poly(DLlactide)-poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)-poly(DL-lactide) (PL-PEO-PPO-PEO-PL) pentablock copolymers have been synthesized in order to obtain precursor architecture suitable for drug delivery systems [98,99]. The chemical composition of PG-PEO-PL provides formation of highly hydroxyl functionalized micelles in aqueous media, taking "hairy" structure as presented in Fig.…”

“…Polymer based micelles generally have spherical shape sized from 10 to 100 nm [100] and core -shell architecture where segments dissolved in a particular solvent form the outer shell stabilizing the inner hydrophobic core [101,102]. Important class of macromolecular surfactants are non-ionogenic block copolymers with polyoxyethylene hydrophilic part, while hydrophobic part is usually built of poly(propylene oxide) (PPO) [103], poly(butylene oxide) (PBO) [104] or biodegradable polymers, such as poly(-benzyl-L-aspartate) (PBLA) [105], poly((L)DL-lactic acid) (PLLA, PDLLA) [98,99,104], poly(lactic-co-glycolic acid) (PLGA) [106] or poly( -caprolactone) (PCL) [107,108]. Hydrophobic cores in the micelles serve as reservoirs of hydrophobic drugs protecting them from contact with aqueous solvents [109].…”