Amphiphilic depsipeptide‐based block copolymers as nanocarriers for controlled release of ibuprofen with doxorubicin

Abstract

Well‐defined amphiphilic multiblock copolymers PDMAEMA‐b‐P(IBMD‐co‐PDO)‐b‐PEG‐b‐P(IBMD‐co‐PDO)‐b‐PDMAEMA [PDMAEMA‐PIBMD‐PPDO‐PEG], based on poly(2‐(dimethylamino)ethyl methacrylate) block (PDMAEMA), poly(3(S)‐isobutyl‐morpholine‐2,5‐dione‐co‐p‐dioxanone) block (P(IBMD‐co‐PDO)), and poly(ethylene glycol) block (PEG) were successfully synthesized by combination of ring‐opening polymerization (using 3(S)‐isobutyl‐morpholine‐2,5‐dione and p‐dioxanone initiated by hydroxyl end of PEG) and atom transfer radical polymerization (ATRP). Furthermore, all these copolymers were characterized by 1H NMR, 13C NMR, Fourier transformed‐infrared, gel permeation chromatography, differential scanning calorimetry, and thermogravimetric analysis measurements. The degradation experiments showed that the molecular weight of PDMAEMA‐PIBMD‐PPDO‐PEG decreased along with degradation time. In addition, these copolymers could readily self‐assemble into nanosized microspheres in phosphate buffered solution. Ibuprofen (IBU) and doxorubicin (DOX) as a kind of combined model drugs were loaded into these microspheres by the combination of ionic interaction and hydrophobic effect. These copolymer microspheres exhibited high loading capacity (LC, up to 26.88%), encapsulation efficiency (EE, up to 61.29%), and sustained release behavior of IBU–DOX in phosphate buffered solution. The results of transmission electron microscopy and dynamic light scattering showed that the microspheres were well‐defined uniform spherical particles with average diameter less than 120 nm. Therefore, it can be envisaged that these copolymer systems are promising candidates for controlled release application. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3213–3226

Synthesis of Well‐Defined Dihydroxy Telechelics by (Co)polymerization of Morpholine‐2,5‐Diones Catalyzed by Sn(IV) Alkoxide

“…The amorphous cooligomers could also serve as solely depsipeptide‐based degradable matrices in controlled drug release systems . Their capability of exhibiting strong physical interactions might contribute to obtain higher drug loading or sustained release . The copolymers providing T g s few degrees above body temperature could also be used for solely depsipeptide‐based smart implants capable of a shape‐memory effect, in which the depsipeptide segment would act as switching segment …”

“…[9] Tin(II) 2-ethylhexanoate (Sn(Oct) 2 ) is the most commonly used catalyst for the polymerization of MDs as well as their copolymerization with other cyclic monomers, that is, lactide and ε-caprolactone. [7,[20][21][22] However, ROP catalyzed by Sn(Oct) 2 still encounters the challenge of poor reaction control of the polymer molecular weight, as well as loss of terminal groups caused by the side reactions resulting from any hydroxyl-containing species and by transesterification reactions (typical inter-and intramolecular reaction and backbiting transesterification and/or chain transfer reactions). [23] Impurities, that is, water and organic acids are diffluent in Telechelics Well-defined dihydroxy telechelic oligodepsipeptides (oDPs), which have a high application potential as building blocks for scaffold materials for tissue engineering applications or particulate carrier systems for drug delivery applications are synthesized by ring-opening polymerization (ROP) of morpholine-2,5-diones (MDs) catalyzed by 1,1,6,6-tetra-n-butyl-1,6-distanna-2,5,7,10-tetraoxacyclodecane (Sn(IV) alkoxide).…”

“…Several nontoxic, organometallic, and enzymatic catalysts as well as initiators have been examined for the synthesis of oDPs . Tin(II) 2‐ethylhexanoate (Sn(Oct) 2 ) is the most commonly used catalyst for the polymerization of MDs as well as their copolymerization with other cyclic monomers, that is, lactide and ε‐caprolactone . However, ROP catalyzed by Sn(Oct) 2 still encounters the challenge of poor reaction control of the polymer molecular weight, as well as loss of terminal groups caused by the side reactions resulting from any hydroxyl‐containing species and by transesterification reactions (typical inter‐ and intramolecular reaction and backbiting transesterification and/or chain transfer reactions) .…”

Electrospun Poly(lactide-co-glycolide-co-3(S)-methyl-morpholine-2,5-dione) Nanofibrous Scaffolds for Tissue Engineering

“…Moreover, the degradation products of MMD including L-amino acids can stimulate the proliferation of endothelial cells via a signal pathway and be properly metabolized by living tissues [42][43][44][45]. Based on the copolymers of MMD with other cyclic monomers, our group have developed some gene delivery systems for promoting the transfection and migration of endothelial cells [42,[46][47][48][49]. However, to the best of our knowledge, the study on electrospun nanofibrous scaffolds from the copolymers of MMD with other cyclic monomers for vascular tissue engineering has not been reported previously.…”

Noncytotoxic polycaprolactone-polyethyleneglycol-ε-poly(l-lysine) triblock copolymer synthesized and self-assembled as an antibacterial drug carrier

“…[7][8][9][10] Recently, more and more attention has been paid to synthesize biodegradable and biocompatible amphiphilic block copolymers to prepare vesicles including antibacterial vesicles. [11][12][13][14][15] Most of the cancer patients have lower resistance to bacterial infections during chemotherapy, which can be fatal to them. 16,17 The antibacterial vesicles can not only be used as a drug carrier, but they are also able to resist bacterial infections.…”