Bioactivable nanocarrier systems have favorable characteristics such as high cellular uptake, target specificity, and an efficient intracellular release mechanism. In this study, we developed a bioreducible methoxy polyethylene glycol (mPEG)-triphenylphosphonium (TPP) conjugate (i.e., mPEG-(ss-TPP) conjugate) as a vehicle for mitochondrial drug delivery. A bioreducible linkage with two disulfide bond-containing end groups was used at one end of the hydrophilic mPEG for conjugation with lipophilic TPP molecules. The amphiphilic mPEG-(ss-TPP) self-assembled in aqueous media, which thereby formed core-shell structured nanoparticles (NPs) with good colloidal stability, and efficiently encapsulated the lipophilic anticancer drug doxorubicin (DOX). The DOX-loaded mPEG-(ss-TPP) NPs were characterized in terms of their physicochemical and morphological properties, drug-loading and release behaviors, in vitro anticancer effects, and mitochondria-targeting capacity. Our results suggest that bioreducible DOX-loaded mPEG-(ss-TPP) NPs can induce fast drug release with enhanced mitochondrial uptake and have a better therapeutic effect than nonbioreducible NPs.
In this study, a series of amphiphilic phospholipid structure-mimetic AB 2 miktoarm copolymers consisting of hydrophilic poly(ethylene glycol) (PEG) and biodegradable poly(trimethylene carbonate) (PTMC) were synthesized and compared with typical linear di-block copolymers in terms of self-assembling and drug carrier properties. All the synthesized polymers were characterized by 1 H NMR, FTIR, GPC and DLS measurements to confirm their chemical structures and found to self-assemble in aqueous media to form spherical micelle structures with about 40~70 nm in diameter. A poorly soluble drug, paclitaxel, as a model drug was loaded into polymer micelles by a solid dispersion method and the drug loading efficiency and content was significantly dependent on the loading conditions and the polymer structures. In particular, the miktoarm polymers demonstrated better drug-loading capacity and colloidal stability than the corresponding di-block copolymers, increasing their potential for drug delivery applications.
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