Drug releasing behavior of hybrid micelles containing polypeptide triblock copolymer

Lin, Jiaping; Zhu, Jiaojun; Chen, Tao; Lin, Shaoliang; Cai, Chunhua; Zhang, Liangshun; Zhuang, Yi; Wang, Xiaosong

doi:10.1016/j.biomaterials.2008.09.010

Cited by 166 publications

(115 citation statements)

References 74 publications

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“…Similar behavior has been reported earlier for other drug-loaded polymeric micelles. 37 It was also important to verify the location of the TPP cation because it should be at the micelle surface to direct them to the mitochondria. Signals at δ 7.4−7.8 ppm in Figure 3D,E confirmed that the TPP cation is located in the corona of the micelles.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Design and Evaluation of Multifunctional Nanocarriers for Selective Delivery of Coenzyme Q10 to Mitochondria

et al. 2011

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Impairments of mitochondrial functions have been associated with failure of cellular functions in different tissues, leading to various pathologies. We report here a mitochondria-targeted nanodelivery system for coenzyme Q10 (CoQ10) that can reach mitochondria and deliver CoQ10 in adequate quantities. Multifunctional nanocarriers based on ABC miktoarm polymers (A = poly(ethylene glycol (PEG), B = polycaprolactone (PCL), and C = triphenylphosphonium bromide (TPPBr)) were synthesized using a combination of click chemistry with ring-opening polymerization, self-assembled into nanosized micelles, and were employed for CoQ10 loading. Drug loading capacity (60 wt %), micelle size (25−60 nm), and stability were determined using a variety of techniques. The micelles had a small critical association concentration and were colloidally stable in solution for more than 3 months. The extraordinarily high CoQ10 loading capacity in the micelles is attributed to good compatibility between CoQ10 and PCL, as indicated by the low Flory−Huggins interaction parameter. Confocal microscopy studies of the fluorescently labeled polymer analog together with the mitochondria-specific vital dye label indicated that the carrier did indeed reach mitochondria. The high CoQ10 loading efficiency allowed testing of micelles within a broad concentration range and provided evidence for CoQ10 effectiveness in two different experimental paradigms: oxidative stress and inflammation. Combined results from chemical, analytical, and biological experiments suggest that the new miktoarm-based carrier provides a suitable means of CoQ10 delivery to mitochondria without loss of drug effectiveness. The versatility of the click chemistry used to prepare this new mitochondria-targeting nanocarrier offers a widely applicable, simple, and easily reproducible procedure to deliver drugs to mitochondria or other intracellular organelles.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Design and Evaluation of Multifunctional Nanocarriers for Selective Delivery of Coenzyme Q10 to Mitochondria

et al. 2011

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“…As a result, the release of physically encapsulated Nap is dramatically accelerated. [ 5 ] However, the release of DOX is mainly controlled by the break of hydrazone bond. As a result, the effect of temperature could be less marked.…”

Section: Full Papermentioning

confidence: 99%

Polypeptide‐Based “Smart” Micelles for Dual‐Drug Delivery: A Combination Study of Experiments and Simulations

Chen

Jiang

Cai

et al. 2014

Adv Healthcare Materials

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A dual-drug-loaded micelle is designed and constructed from a mixture of poly(propylene oxide)-b-poly(γ-benzyl-l-glutamate)-b-poly(ethylene glycol) (PPO-b-PBLG-b-PEG) triblock terpolymers and two model drugs, doxorubicin (DOX) and naproxen (Nap). In the micelles, the DOX is chemically linked to the PBLG backbones through an acid-cleavable hydrazone bond, whereas the Nap is physically encapsulated in the cores. The drug loading and releasing behaviors of the dual-drug-loaded micelles as well as single drug-loaded micelles (DOX-conjugated or Nap-loaded micelles) are studied. The structures of micelles are characterized by means of microscopies and dynamic light scattering, and further examined by dissipative particle dynamics (DPD) simulations. It is revealed that the micelles possess a core-shell-corona structure in which the PPO/Nap, PBLG/DOX, and PEG aggregate to form the core, shell, and corona, respectively. In vitro studies reveal that the release of DOX and Nap is pH- and thermosensitive. Such drug releasing behaviors are also examined by DPD simulations, and more information regarding the mechanism is obtained. In addition, the bio-related properties such as cellular uptake of the micelles and biocompatibility of the deliveries are evaluated. The results show that the dual-drug-loaded micelles are biocompatible at normal physiological conditions and retain the anti-cancer efficiency.

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“…Using this naturally responsive feature, researchers prepared pH responsive aggregates such as micelle and vesicles. [24][25][26][27][28] Here, we will mainly focus on recent developments of design and responsive mechanism of stimuli-responsive polypeptides other than pH.…”

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confidence: 99%

Stimuli‐responsive polypeptide materials prepared by ring‐opening polymerization of α‐amino acid N‐carboxyanhydrides

Zhang

2013

J Polym Sci B Polym Phys

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Design and synthesis of biodegradable stimuli-responsive polypeptides are important areas considering their promising applications in biomedical fields. This article summarizes the most recent progresses in the development of stimuli-responsive polypeptide materials prepared via ringopening polymerization of a-amino acid N-carboxyanhydrides. We discuss the design, synthesis and structure-property correlation of emerging materials including thermo-responsive, redox-responsive, photo-responsive and biomolecule responsive polypeptides. Considering the unique structural features of amino acids, we try to emphasize that the thermo-responsive properties not only depend on the amino acid structure but also rely on the secondary structures of polypeptides. V C 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 546-555

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Drug releasing behavior of hybrid micelles containing polypeptide triblock copolymer

Cited by 166 publications

References 74 publications

Design and Evaluation of Multifunctional Nanocarriers for Selective Delivery of Coenzyme Q10 to Mitochondria

Design and Evaluation of Multifunctional Nanocarriers for Selective Delivery of Coenzyme Q10 to Mitochondria

Polypeptide‐Based “Smart” Micelles for Dual‐Drug Delivery: A Combination Study of Experiments and Simulations

Stimuli‐responsive polypeptide materials prepared by ring‐opening polymerization of α‐amino acid N‐carboxyanhydrides

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