Drug release kinetics, cell uptake, and tumor toxicity of hybrid VVVVVVKK peptide-assembled polylactide nanoparticles

Jabbari, Esmaiel; Yang, Xiaoming; Moeinzadeh, Seyedsina; He, Xuezhong

doi:10.1016/j.ejpb.2012.12.012

Cited by 42 publications

(29 citation statements)

References 91 publications

(110 reference statements)

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“…The number of peptides in a peptide/lactidecapped PEG conjugate was determined using the acrylate/ PEG molar ratios before and after conjugation as previously described. 28 The average number of peptides per conjugate for L0, L2, L4, and L6 macromers was 0.57, 0.49, 0.52, and 0.45, respectively. Several studies have demonstrated that >95% of acrylated PEG/peptide conjugates are integrated in PEGDA hydrogel network during photocrosslinking.…”

Section: Resultsmentioning

confidence: 99%

“…25,28 The number of lactide repeat units per chain end of the lactide-capped PEG macromer was determined from the ratio of the peaks at 1.6 and 5.2 ppm (lactide hydrogens) to those at 3.6 and 4.3 ppm (PEG hydrogens). 25 The average number of lactide repeat units per chain end for L2, L4, and L6 macromers was 1.9, 3.6, and 5.6, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…The number of peptides per lactide-capped PEG chain was determined by 1 H-NMR as we described previously. 28 The conjugate is hereinafter referred to as PLn where ''P,'' ''L,'' and ''n'' stand for BMP-2 peptide, lactide-capped PEG macromer, and number of lactide monomers per chain end, respectively.…”

Section: Bmp-2 Peptide Synthesis and Conjugation To The Macromermentioning

confidence: 99%

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Experimental and Computational Investigation of the Effect of Hydrophobicity on Aggregation and Osteoinductive Potential of BMP-2-Derived Peptide in a Hydrogel Matrix

Moeinzadeh

Barati²,

Sarvestani³

et al. 2015

Tissue Engineering Part A

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An attractive approach to reduce the undesired side effects of bone morphogenetic proteins (BMPs) in regenerative medicine is to use osteoinductive peptide sequences derived from BMPs. Although the structure and function of BMPs have been studied extensively, there is limited data on structure and activity of BMP-derived peptides immobilized in hydrogels. The objective of this work was to investigate the effect of concentration and hydrophobicity of the BMP-2 peptide, corresponding to residues 73-92 of the knuckle epitope of BMP-2 protein, on peptide aggregation and osteogenic differentiation of human mesenchymal stem cells encapsulated in a polyethylene glycol (PEG) hydrogel. The peptide hydrophobicity was varied by capping PEG chain ends with short lactide segments. The BMP-2 peptide with a positive index of hydrophobicity had a critical micelle concentration (CMC) and formed aggregates in aqueous solution. Based on simulation results, there was a slight increase in the concentration of free peptide in solution with 1000-fold increase in peptide concentration. The dose-osteogenic response curve of the BMP-2 peptide was in the 0.0005-0.005 mM range, and osteoinductive potential of the BMP-2 peptide was significantly less than that of BMP-2 protein even at 1000-fold higher concentrations, which was attributed to peptide aggregation. Further, the peptide or PEG-peptide aggregates had significantly higher interaction energy with the cell membrane compared with the free peptide, which led to a higher nonspecific interaction with the cell membrane and loss of osteoinductive potential. Conjugation of the BMP-2 peptide to PEG increased CMC and osteoinductive potential of the peptide whereas conjugation to lactide-capped PEG reduced CMC and osteoinductive potential of the peptide. Experimental and simulation results revealed that osteoinductive potential of the BMP-2 peptide is correlated with its CMC and the free peptide concentration in aqueous medium and not the total concentration.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Bmp-2 Peptide Synthesis and Conjugation To The Macromermentioning

confidence: 99%

See 1 more Smart Citation

Experimental and Computational Investigation of the Effect of Hydrophobicity on Aggregation and Osteoinductive Potential of BMP-2-Derived Peptide in a Hydrogel Matrix

Moeinzadeh

Barati²,

Sarvestani³

et al. 2015

Tissue Engineering Part A

Self Cite

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show abstract

“…Moreover, the experiments have demonstrated that the PLA-V6K2 nanoparticles conjugated with anticancer drugs have higher toxicity to cancer cells and no toxicity to normal cells compared with free doxorubicin or paclitaxel and pure PLA nanoparticles conjugates. Therefore, this study demonstrated the higher efficacy of these PLA-V6K2 nanoparticles for anticancer drug delivery that could be potentially useful in cancer therapy [123].…”

Section: Anticancer Drug Deliverymentioning

confidence: 99%

Peptide Self-Assembled Nanostructures for Drug Delivery Applications

Fan

Shen

et al. 2017

Journal of Nanomaterials

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Peptide self-assembled nanostructures are very popular in many biomedical applications. Drug delivery is one of the most promising applications among them. The tremendous advantages for peptide self-assembled nanostructures include good biocompatibility, low cost, tunable bioactivity, high drug loading capacities, chemical diversity, specific targeting, and stimuli responsive drug delivery at disease sites. Peptide self-assembled nanostructures such as nanoparticles, nanotubes, nanofibers, and hydrogels have been investigated by many researchers for drug delivery applications. In this review, the underlying mechanisms for the self-assembled nanostructures based on peptides with different types and structures are introduced and discussed. Peptide self-assembled nanostructures associated promising drug delivery applications such as anticancer drug and gene drug delivery are highlighted. Furthermore, peptide self-assembled nanostructures for targeted and stimuli responsive drug delivery applications are also reviewed and discussed.

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“…In this study, we have explored new thermoresponsive polymeric micelles (Ward and Georgiou, 2011;Dhar et al, 2011;Jabbari et al, 2013) PNIPAAm-VP to overcome some of the limitations of currently available polymer micelles. The objectives of this work were to synthesize PNIPAAm-VP nanoparticles and to study the efficacy enhancement on cancer cell lines MCF-7 and B16F0 and size distribution properties of the particles.…”

Section: Introductionmentioning

confidence: 99%

Development of Polymeric Nanopaclitaxel and Comparison with Free Paclitaxel for Effects on Cell Proliferation of MCF-7 and B16F0 Carcinoma Cells

Yadav

Anwar²,

Garg³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Paclitaxel is hydrophobic in nature and is recognized as a highly toxic anticancer drug, showing adverse effects in normal body sites. In this study, we developed a polymeric nano drug carrier for safe delivery of the paclitaxel to the cancer that releases the drug in a sustained manner and reduces side effects. N-isopropylacrylamide/ vinyl pyrrolidone (NIPAAm/VP) nanoparticles were synthesized by radical polymerization. Physicochemical characterization of the polymeric nanoparticles was conducted using dynamic light scattering, transmission electron microscopy, scanning electron microscopy and nuclear magnetic resonance, which confirmedpolymerization of formulated nanoparticles. Drug release was assessed using a spectrophotometer and cell viability assays were carried out on the MCF-7 breast cancer and B16F0 skin cancer cell lines. NIPAAm/ VP nanoparticles demonstrated a size distribution in the 65-108 nm range and surface charge measured -15.4 mV. SEM showed the nanoparticles to be spherical in shape with a slow drug release of ~70% in PBS at 38°C over 96 h. Drug loaded nanoparticles were associated with increased viability of MCF-7 and B16F0 cells in comparison to free paclitaxel. Nano loaded paclitaxel shows high therapeutic efficiency by sustained release action for the longer period of time, i increasing its efficacy and biocompatibility for human cancer therapy. Therefore, paclitaxel loaded (NIPAAm/VP) nanoparticles may provide opportunities to expand delivery of the drug for clinical selection.

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Drug release kinetics, cell uptake, and tumor toxicity of hybrid VVVVVVKK peptide-assembled polylactide nanoparticles

Cited by 42 publications

References 91 publications

Experimental and Computational Investigation of the Effect of Hydrophobicity on Aggregation and Osteoinductive Potential of BMP-2-Derived Peptide in a Hydrogel Matrix

Experimental and Computational Investigation of the Effect of Hydrophobicity on Aggregation and Osteoinductive Potential of BMP-2-Derived Peptide in a Hydrogel Matrix

Peptide Self-Assembled Nanostructures for Drug Delivery Applications

Development of Polymeric Nanopaclitaxel and Comparison with Free Paclitaxel for Effects on Cell Proliferation of MCF-7 and B16F0 Carcinoma Cells

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