Synthesis and Evaluation of Water-Soluble Polymeric Bone-Targeted Drug Delivery Systems

Wang, Dong; Miller, Scott C.; Sima, Monika; Kopečková, Pavla; Kopeček, Jindřich

doi:10.1021/bc034090j

Cited by 149 publications

(139 citation statements)

References 25 publications

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“…The amount of D-Asp 8 was calculated by calibration with standard D-Asp. 8 (MA-Gly-Gly-D-Asp 8 ) was synthesized by manual solid phase peptide synthesis (SPPS) using Fmoc/tBu strategy on 2-chlortrityl chloride resin. 15 After the attachment of the eighth D-aspartic acid residue onto the resin, MA-GlyGly-OH was coupled to the N-terminus of the resin-bound peptide with the similar PyBOP® coupling procedure.…”

Section: Characterization Of the Synthetic Productsmentioning

confidence: 99%

Pharmacokinetic and Biodistribution Studies of a Bone-Targeting Drug Delivery System Based onN-(2-Hydroxypropyl)methacrylamide Copolymers

et al. 2006

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Osteotropicity of novel bone-targeted HPMA copolymer conjugates has been demonstrated previously with bone histomorphometric analysis. The pharmacokinetics and biodistribution of this delivery system were investigated in the current study with healthy young BALB/c mice. The 125 Ilabeled bone-targeted and control (non-targeted) HPMA copolymers were administered intravenously to mice and their distribution to different organs and tissues were followed using a gamma counter and single photon emission computed tomography (SPECT). Both the invasive and non-invasive data further confirmed that the incorporation of D-aspartic acid octapeptide (D-Asp 8 ) as bone-targeting moiety could favorably deposit the HPMA copolymers to the entire skeleton, especially to the high bone turnover sites. To evaluate the influence of molecular weight, three fractions (M w of 24, 46, and 96 kDa) of HPMA copolymer -D-Asp 8 conjugate were prepared and evaluated. Higher molecular weight of the conjugate enhanced the deposition to bone due to the prolonged half-life in circulation, but it weakened the bone-selectivity. A higher content of bonetargeting moiety (D-Asp 8 ) in the conjugate is desirable to achieve superior hard tissue selectivity. Further validation of the bone-targeting efficacy of the conjugates in animal models of osteoporosis and other skeletal diseases is needed in the future.

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Section: Characterization Of the Synthetic Productsmentioning

confidence: 99%

Pharmacokinetic and Biodistribution Studies of a Bone-Targeting Drug Delivery System Based onN-(2-Hydroxypropyl)methacrylamide Copolymers

et al. 2006

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“…18 A short peptide sequence of repetitive aspartic acid (4-10 amino acids) has been shown to interact exclusively with bone in vitro and in vivo. [19][20][21][22] (Asp) 8 is biodegradable, biocompatible, and has shown strong affinity to more crystalline hydroxyapatite and bone surface. 19,21,22 Therefore, (Asp) 8 -linked PEG-PCL nanoparticles can be a potent hydrophobic anticancer drug carrier targeting the bone niche.…”

Section: Introductionmentioning

confidence: 99%

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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“…To study the binding of these conjugates to bone, an in vitro HAP binding assay was set up using in vitro HAP binding methods (Wang et al, 2003). The conjugates were dissolved in water with various precise concentrations and the adsorption amounts were determined by a UV spectrophotometer at 274 nm to obtain the A-C linear regression equation.…”

Section: In Vitro Hap Binding Assaymentioning

confidence: 99%

Dual-targeting delivery system for bone cancer: synthesis and preliminary biological evaluation

et al. 2012

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Synthesis and Evaluation of Water-Soluble Polymeric Bone-Targeted Drug Delivery Systems

Cited by 149 publications

References 25 publications

Pharmacokinetic and Biodistribution Studies of a Bone-Targeting Drug Delivery System Based onN-(2-Hydroxypropyl)methacrylamide Copolymers

Pharmacokinetic and Biodistribution Studies of a Bone-Targeting Drug Delivery System Based onN-(2-Hydroxypropyl)methacrylamide Copolymers

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

Dual-targeting delivery system for bone cancer: synthesis and preliminary biological evaluation

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Synthesis and Evaluation of Water-Soluble Polymeric Bone-Targeted Drug Delivery Systems

Cited by 149 publications

References 25 publications

Pharmacokinetic and Biodistribution Studies of a Bone-Targeting Drug Delivery System Based onN-(2-Hydroxypropyl)methacrylamide Copolymers

Pharmacokinetic and Biodistribution Studies of a Bone-Targeting Drug Delivery System Based onN-(2-Hydroxypropyl)methacrylamide Copolymers

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

Dual-targeting delivery system for bone cancer: synthesis and preliminary biological evaluation

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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