Novel Polymeric Micelles of AB₂ Type α-Methoxy-Poly(ethylene glycol)-b-Poly(γ-benzyl-L-glutamate)₂ Copolymers as Tamoxifen Carriers

Abstract

A novel AB2 type amphiphilic miktoarm-star copolymer of alpha-methoxy-poly(ethylene glycol)-b-poly(gamma-benzyl-L-glutamate)2 was synthesized by ring-opening polymerization of gamma-benzyl-L-glutamate N-carboxyanhydride. The polymerization was initiated by the terminal amino groups of alpha-methoxy-omega-N,N-bis(aminoethyl) poly(ethylene glycol). Structural properties of the star copolymer were confirmed by IR and 1H NMR spectra. Polymeric micelles were prepared in aqueous solution by dialysis method. Spherical core/shell structure of the micelles was confirmed by transmission electron microscopy and 1H NMR spectra. Dynamic light scattering results indicated that the sizes of the micelles were mostly in the range of 20-50 nm with a narrow size distribution. With the molecular weight of each poly(gamma-benzyl-L-glutamate) block increasing from 2.0 kDa to 13.2 kDa, Tamoxifen loading content increased from 7.34% to 20.30%, corresponding to the increase of Tamoxifen entrapment efficiency from 4.11% to 29.13% and Tamoxifen solubility in water from 11.75 microg/ml to 82.23 microg/ml. In vitro release study of Tamoxifen-loaded micelles at 37 degrees C demonstrated that Tamoxifen-release from micelles at pH 5.0 was much faster than that at pH 7.4. These polymeric micelles are expected to be utilized as promising new drug carriers.

Miktoarm Star Polymer Based Multifunctional Traceable Nanocarriers for Efficient Delivery of Poorly Water Soluble Pharmacological Agents

“…The size of curcumin‐loaded micelles was larger than that of the empty micelles which suggested curcumin incorporation into the micelle core (Table ) . Curcumin loading in these micelles was ≈3–5 wt% with an encapsulation efficiency of 27–55 wt% which is comparable to other miktoarm polymer micelles with similar drug loading capacities . Polymers with PEG 2000 and PCL 21000 precipitated in aqueous solution and did not form micelles.…”

Miktoarm Star Polymers: Branched Architectures in Drug Delivery

“…It has been argued that the branching architecture of miktoarm stars has favourable effects on drug loading and release properties, and increasing hydrophobic chain length can lead to an increase in drug encapsulation and prolonged drug release [ 32 , 48 , 62 ]. However, long hydrophobic segments may also prohibit micellar hydrophilic surface coverage [ 13 , 52 , 134 ]. This has been mainly a concern for diblock copolymers, and it can be lessened by making use of the branched architectures.…”

Self-Assembled Micelles Composed of Doxorubicin Conjugated Y-Shaped PEG-Poly(glutamic acid)2 Copolymers via Hydrazone Linkers

“…Simple alterations in the morphology, size, release profile or drug-loading content of nano-carriers can be readily achieved by modifying parameters like the generations of dendrimers [2,3], grafting percentage of graft copolymers [4,5] and the conformation of the blocks [6,7]. Recently, miktoarm-star copolymers with branches at the junction point of the linear copolymers have aroused increasing interest [8,9,10,11]. These non-linear copolymers exhibited unique self-assembly behaviors believed to be based on the conformational entropy reduction caused by the introduction of branches at the junction point [10,12].…”

“…These non-linear copolymers exhibited unique self-assembly behaviors believed to be based on the conformational entropy reduction caused by the introduction of branches at the junction point [10,12]. The architecture dependent self-assemble of these polymers affords conventional and non-conventional nano-structures like micelles [8,10,11], polymersomes [9,13], multicompartment micelles [14] and wormlike micelles [15]. More recently, polyamino acids were used to build a variety of polymers due to their high biocompatibility.…”

“…Another AB 2 type copolymer (mPEG-b-PBLG 2 ) was synthesized by Li et al . [8], and the tamoxifen loaded micelles also exhibited a sustained release pattern.…”