Comparison of micelles formed by amphiphilic star block copolymers prepared in the presence of a nonmetallic monomer activator

Abstract

In this article, we describe the synthesis of PEG‐b‐polyester star block copolymers via ring‐opening polymerization (ROP) of ester monomers initiated at the hydroxyl end group of the core poly(ethylene glycol) (PEG) using HCl Et2O as a monomer activator. The ROP of ε‐caprolactone (CL), trimethylene carbonate (TMC), or 1,4‐dioxan‐2‐one (DO) was performed to synthesize PEG‐b‐polyester star block copolymers with one, two, four, and eight arms. The PEG‐b‐polyester star block copolymers were obtained in quantitative yield, had molecular weights close to the theoretical values calculated from the molar ratio of ester monomers to PEG, and exhibited monomodal GPC curves. The crystallinity of the PEG‐b‐polyester star block copolymers was determined by differential scanning calorimetry and X‐ray diffraction. Copolymers with a higher arm number had a higher tendency toward crystallization. The crystallinity of the PEG‐b‐polyester star block copolymers also depended on the nature of the polyester block. The CMCs of the PEG‐b‐PCL star block copolymers, determined from fluorescence measurements, increased with increasing arm number. The CMCs of the four‐arm star block copolymers with different polyester segments increased in the order 4a‐PEG‐b‐PCL < 4a‐PEG‐b‐PDO < 4a‐PEG‐b‐PLGA < 4a‐PEG‐b‐PTMC, suggesting a relationship between CMC and star block copolymer crystallinity. The partition equilibrium constant, Kv, which is an indicator of the hydrophobicity of the micelles of the PEG‐polyester star block copolymers in aqueous media, increased with decreasing arm number and increasing crystallinity. A key aspect of the present work is that we successfully prepared PEG‐b‐polyester star block copolymers by a metal‐free method. Thus, unlike copolymers synthesized by ROP using a metal as the monomer activator, our copolymers do not contain traces of metals and hence are more suitable for biomedical applications. Moreover, we confirmed that the PEG‐b‐polyester star block copolymers form micelles and hence may be potential hydrophobic drug delivery vehicles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2084–2096, 2008

Star‐shaped amphiphilic block polyurethane with pentaerythritol core for a hydrophobic drug delivery carrier

“…CMC is an important parameter to evaluate the stability of micelles as drug delivery carriers. The lower the CMC is, the stronger the anti‐dilution ability of micelles is in body fluid . In order to measure the CMC of SAPU, the intensity ratio of the peak at 337.0 nm to the peak at 334.5 nm ( I 337.0 / I 334.5 ) from excitation spectra was plotted against the logarithm of micelle concentration (Fig.…”

“…However, many reports have mainly focused on researching linear amphiphilic polyurethane micelles as delivery vehicles of drugs and genes . Generally, linear amphiphilic copolymers have a larger critical micelle concentration (CMC) and micelles are formed only through physical interaction, which are not beneficial to maintaining micellar stability . Because the micellar structure will be easily disrupted and the burst release of entrapped drugs will happen after intravenous injection into the bloodstream, the bioavailability of drugs will be reduced and the large drug concentration fluctuation will produce toxic side effects to healthy tissue .…”

Dry powder cationic lipopolymeric nanomicelle inhalation for targeted delivery of antitubercular drug to alveolar macrophage

“…This is in accordance with the general observation that crystallization of individual blocks in star shaped copolymer micelles is hampered, resulting in shifting of the endothermic curve. 36,37 The SABPEI 5050 combination was found to be more crystalline, indicating the ability of folded SA moieties in complete crystallization. Earlier studies on star shaped micelles revealed that micellization ability is directly proportional to crystallinity.…”

AB2‐type amphiphilic block copolymers composed of poly(ethylene glycol) and poly(N‐isopropylacrylamide) via single‐electron transfer living radical polymerization: Synthesis and characterization

“…Recently, micellization of block copolymers with a complex architecture was investigated 11, 12. Typically, star‐shaped (AB n ‐type) block copolymers exhibit fundamentally different micellization behavior when compared with the corresponding linear counterparts 13. Their micellization is less favorable with a considerably lower association number.…”