Development of biodegradable polymeric implants of RGD-modified PEG-PAMAM-DOX conjugates for long-term intratumoral release

Wang, Ke; Zhang, Xiaofeng; Zhang, Lihong; Qian, Lili; Liu, Chang; Zheng, Jiajun; Jiang, Yanyan

doi:10.3109/10717544.2014.895457

Cited by 31 publications

(19 citation statements)

References 40 publications

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“…of the system (conjugated or co-administrated) exhibited better tumor penetration and accumulation and this translated to higher survival rates in vivo [76]. Even given this success, further studies explored the added potential of RGD-PPCD loaded onto poly(lactic-co-glycolic acid)-poly(lactic acid) (PLGA-PLA) implants for long-term intratumoral release [77]. These implants led to better intratumoral drug accumulation (~4-fold compared to free DOX implants) and consequently, they exhibited enhanced antitumor activity in C6 glioma xenografts (~2-and ~1.3-fold lower tumor volume when compare to DOX and untargeted implants, respectively).…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Modulating angiogenesis with integrin-targeted nanomedicines

Duro‐Castaño

Gallon

Decker

et al. 2017

Advanced Drug Delivery Reviews

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Targeting angiogenesis-related pathologies, which include tumorigenesis and metastatic processes, has become an attractive strategy for the development of efficient guided nanomedicines. In this respect, integrins are cell-adhesion molecules involved in angiogenesis signaling pathways and are overexpressed in many angiogenic processes. Therefore, they represent specific biomarkers not only to monitor disease progression but also to rationally design targeted nanomedicines. Arginine-glycine-aspartic (RGD) containing peptides that bind to specific integrins have been widely utilized to provide ligand-mediated targeting capabilities to small molecules, peptides, proteins, and antibodies, as well as to drug/imaging agent-containing nanomedicines, with the final aim of maximizing their therapeutic index. Within this review, we aim to cover recent and relevant examples of different integrin-assisted nanosystems including polymeric nanoconstructs, liposomes, and inorganic nanoparticles applied in drug/gene therapy as well as imaging and theranostics. We will also critically address the overall benefits of integrin-targeting.

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Section: Accepted M Manuscriptmentioning

confidence: 99%

Modulating angiogenesis with integrin-targeted nanomedicines

Duro‐Castaño

Gallon

Decker

et al. 2017

Advanced Drug Delivery Reviews

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“…PEG has been widely used as a drug carrier and addition of PEG can facilitate the dissolution and increase the release rate of the drug from implants by promoting the water diffusion into the implants. 25 – 27 …”

Section: Discussionmentioning

confidence: 99%

Enhanced antitumor efficacy of poly(D,L-lactide-co-glycolide)-based methotrexate-loaded implants on sarcoma 180 tumor-bearing mice

Gao¹,

Xia²,

Zhang³

et al. 2017

DDDT

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PurposeMethotrexate is widely used in chemotherapy for a variety of malignancies. However, severe toxicity, poor pharmacokinetics, and narrow safety margin of methotrexate limit its clinical application. The aim of this study was to develop sustained-release methotrexate-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation.Materials and methodsWe prepared the implants containing methotrexate, poly(D,L-lactide-co-glycolide), and polyethylene glycol 4000 with the melt-molding technique. The implants were characterized with regards to drug content, morphology, in vitro, and in vivo release profiles. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were carried out to investigate the physicochemical properties of the implants. Furthermore, the antitumor activity of the implants was tested in a sarcoma 180 mouse model.ResultsThe implants were prepared as solid rods. Scanning electron microscopy images showed a smooth surface of the implant, suggesting that methotrexate was homogeneously dispersed in the polymeric matrix. The results of DSC and FTIR indicated that no significant interaction between methotrexate and the polymer was observed in the implants. Both in vitro and in vivo release profiles of the implants were characterized by burst release followed by sustained release of methotrexate. Intratumoral implantation of methotrexate-loaded implants could efficiently delay tumor growth. Moreover, an increase in the dose of implants led to a higher tumor suppression rate without additional systemic toxicity.ConclusionThese results demonstrate that methotrexate-loaded implants had significant antitumor efficacy in a sarcoma 180 mouse model without dose-limiting side effects, and suggest that the implants could be potentially applied as an intratumoral delivery system to treat cancer.

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“…A number of RGD sequences containing cyclic peptides, such as RGDyC [45], RGDfK [46], and RGD-DTyr-C [47], have been identified to possess improved activity profiles and been extensively applied in polymer-drug conjugates (shown in Table 2). These cyclic peptides could increase tumor targeting and deeply increased the antitumor efficacy of drug in vitro and in vivo.…”

Section: Peptide-targeted Polymer-drug Conjugatesmentioning

confidence: 99%