Aspartic acid-based modified PLGA–PEG nanoparticles for bone targeting: In vitro and in vivo evaluation

Fu, Yaw-Syan; Fu, Tzu Fun; Wang, Hung‐Jen; Lin, Che; Lee, Gang Hui; Wu, Shun-Cheng; Wang, Chih Kuang

doi:10.1016/j.actbio.2014.07.015

Cited by 57 publications

(32 citation statements)

References 36 publications

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“…35,42 In this study, (Asp) 8 -PEG-PCL nanoparticles showed similar binding affinity to hydroxyapatite in vitro, as reported in previous studies using polyaspartic acid peptide-linked nanoparticles. 35,42 Intravenously administered (Asp) 8 -PEG-PCL and PEG-PCL nanoparticles were able to reach the bone niche; due to bone surface specificity of the (Asp) 8 -PEG-PCL nanoparticles, they accumulated in higher amount in comparison to the PEG-PCL nanoparticles. Interestingly, in vivo bone surface binding affinity of (Asp) 8 -PEG-PCL was stronger (2.8-fold) than that of (Asp) 3 -PEG-PLGA nanoparticles (1.5-fold) reported previously.…”

Section: Discussionsupporting

confidence: 67%

“…41 Bone-targeting nanoparticles should be 70-200 nm in size to reach the bone tissues by passing through the vascular structures and live organs of interest. 42 (Asp) 8 -PEG-PCL nanoparticles designed in this study had the hydrophilic surface of PEG and the hydrophilic The effect of nanoparticles on erythrocyte aggregation indicates hemocompatibility of the nanoparticles. 43 Copolymer containing PEG-PCL has been reported to be hemocompatible and biocompatible.…”

Section: Discussionmentioning

confidence: 99%

“…35 Briefly, hydroxyapatite was suspended in ultrapure water at a concentration of 5 mg/mL. Hydrophobic fluorescent Nile red added PEG-PCL or (Asp) 8 -PEG-PCL (the weight ratio is 1:10) was added to the crystallized hydroxyapatite suspensions and mixed at room temperature by rotating for 24 h. The mixture was shaken for 30 min, 1 h, 2 h, 7 h, and 24 h, respectively.…”

Section: In Vitro Hydroxyapatite Binding Assaymentioning

confidence: 99%

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Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

Liu¹,

Zeng²,

Shi

et al. 2017

IJN

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Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp) 8 , has a strong affinity to bone surface. The aim of this study was to synthesize (Asp) 8 -PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone. 1 H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp) 8 -PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp) 8 -PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp) 8 -PEG-PCL nanoparticles by cancer cells. (Asp) 8 -PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10–800 μg/mL. (Asp) 8 -PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp) 8 -PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp) 8 -PEG-PCL. (Asp) 8 -PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp) 8 -PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic ability in vitro. Therefore, (Asp) 8 -PEG-PCL nanoparticles could be a potent carrier of hydrophobic anticancer drugs to treat the cancer metastasized to bone.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: In Vitro Hydroxyapatite Binding Assaymentioning

confidence: 99%

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Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

Liu¹,

Zeng²,

Shi

et al. 2017

IJN

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“…The binding capacity of NPs to HAp was evaluated using a method similar to that described in some previous reports. 26,27 In brief, NPs loaded with the hydrophobic fluorescent dye ODA-FITC were used at a dilution of 4 mL (0. …”

Section: Alizarin Red S Assaymentioning

confidence: 99%

Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system

Wang¹,

Liu²,

Tao³

et al. 2015

IJN

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Purpose Nanoparticles (NPs) that target bone tissue were developed using poly(lactic-co-glycolic acid) (PLGA) copolymers and tetracycline (TC)-based bone-targeting moieties. These NPs are expected to enable the transport of drugs, such as simvastatin (SIM), for the treatment of osteoporosis. Methods The molecular structures of TC–PLGA were validated by 1 H-NMR, and the SIM-loaded NPs were prepared using the solvent emulsification method. The surface properties, cytotoxicity, cellular uptake, cell mineralization, bone targeting potential, and animal pharmacodynamics of the TC–PLGA NPs were evaluated and compared to those of PLGA NPs. Results It was confirmed that the average particle size of the NPs was approximately 220 nm. In phosphate-buffered saline (PBS, pH 7.4), the SIM-loaded NPs exhibited a cumulative release of up to 80% within 72 hours. An in vitro cell evaluation indicated that the NPs had an excellent cellular uptake capacity and showed great biocompatibility with MC3T3-E1 cells, thereby reducing the cytotoxic effects of SIM. The cell mineralization assay showed that the SIM-loaded NPs induced osteogenic differentiation and mineralized nodule formation in MC3T3-E1 cells, thereby achieving the same effect as SIM. Preliminary findings from in vitro and in vivo bone affinity assays indicated that the TC–PLGA NPs may display increased bone-targeting efficiency compared to PLGA NPs lacking a TC moiety. The use of SIM-loaded TC–PLGA NPs in treating osteoporosis was tested through animal pharmacodynamics analyses performed in ovariectomized rats, and the results suggested that the SIM-loaded TC–PLGA NPs can improve the curative effects of SIM on the recovery of bone mineral density compared to either SIM-loaded PLGA NPs or SIM alone. Conclusion Bone-targeting NPs, which were based on the conjugation of TC to PLGA copolymers, have the ability to target bone. These NPs may be developed as a delivery system for hydrophobic drugs, and they are expected to improve the curative effects of drugs, reduce the administered drug doses, and reduce side effects in other organs.

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“…In these experiments, curcumin showed a lower cytotoxicity in C6 and HeLa cells than the corresponding NPs due to the improved biocompatibility and affinity to cells of the PEG-PLGA incorporated in the NPs. 24 The cHP/Cur-NPs were more lethal to C6 cells than Cur-NPs in the low integrin-expressing HeLa cells. In HeLa cells, no significant difference was observed in the cytotoxicity between Cur-NPs and cHP/Cur-NPs in most cases, possibly because the RGD sequence peptides can bind to integrin-α v β 3 in C6 cells but not in HeLa cells, 25,26 and the …”

mentioning

confidence: 99%

Cyclic hexapeptide-conjugated nanoparticles enhance curcumin delivery to glioma tumor cells and tissue

Zhang¹,

Li²,

Hua³

et al. 2017

IJN

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Glioma has one of the highest mortality rates among primary brain tumors. The clinical treatment for glioma is very difficult due to its infiltration and specific growth locations. To achieve improved drug delivery to a brain tumor, we report the preparation and in vitro and in vivo evaluation of curcumin nanoparticles (Cur-NPs). The cyclic hexapeptide c(RGDf(N-me) VK)-C (cHP) has increased affinity for cells that overexpress integrins and was designed to target Cur-NPs to tumors. Functional polyethyleneglycol-modified poly( d , l -lactide-co-glycolide) (PEG-PLGA) conjugated to cHP was synthesized, and targeted Cur-NPs were prepared using a self-assembly nanoprecipitation process. The physicochemical properties and the in vitro cytotoxicity, accuracy, and penetration capabilities of Cur-NPs targeting cells with high levels of integrin expression were investigated. The in vivo targeting and penetration capabilities of the NPs were also evaluated against glioma in rats using in vivo imaging equipment. The results showed that the in vitro cytotoxicity of the targeted cHP-modified curcumin nanoparticles (cHP/Cur-NPs) was higher than that of either free curcumin or non-targeted Cur-NPs due to the superior ability of the cHP/Cur-NPs to target tumor cells. The targeted cHP/Cur-NPs, c(RGDf(N-me)VK)-C-modified Cur-NPs, exhibited improved binding, uptake, and penetration abilities than non-targeting NPs for glioma cells, cell spheres, and glioma tissue. In conclusion, c(RGDf(N-me)VK)-C can serve as an effective targeting ligand, and cHP/Cur-NPs can be exploited as a potential drug delivery system for targeting gliomas.

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Aspartic acid-based modified PLGA–PEG nanoparticles for bone targeting: In vitro and in vivo evaluation

Cited by 57 publications

References 36 publications

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system

Cyclic hexapeptide-conjugated nanoparticles enhance curcumin delivery to glioma tumor cells and tissue

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Aspartic acid-based modified PLGA–PEG nanoparticles for bone targeting: In vitro and in vivo evaluation

Cited by 57 publications

References 36 publications

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (&epsilon;-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (&epsilon;-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system

Cyclic hexapeptide-conjugated nanoparticles enhance curcumin delivery to glioma tumor cells and tissue

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Resources

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Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone