Biodistribution of radiolabeled polyglutamic acid and PEG-polyglutamic acid nanocapsules

Abellan-Pose, Raquel; Rodríguez-Évora, María; Vicente, Sara; Csaba, Nœmi; Évora, Carmen; Alonso, Marı́a José; Delgado, Araceli

doi:10.1016/j.ejpb.2016.11.015

Cited by 18 publications

(17 citation statements)

References 34 publications

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“…The mechanical performance of these hybrid valves was higher while the calcification was lower. While PGA has been used in vivo as nanocapsules for therapeutic gene or for anti-cancer drug delivery in mice model [203][204][205], it has not been tested as a scaffold in vivo.…”

Section: Bioplastics Polymers As Implants In Vivomentioning

confidence: 99%

Recent Advances in Bioplastics: Application and Biodegradation

et al. 2020

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The success of oil-based plastics and the continued growth of production and utilisation can be attributed to their cost, durability, strength to weight ratio, and eight contributions to the ease of everyday life. However, their mainly single use, durability and recalcitrant nature have led to a substantial increase of plastics as a fraction of municipal solid waste. The need to substitute single use products that are not easy to collect has inspired a lot of research towards finding sustainable replacements for oil-based plastics. In addition, specific physicochemical, biological, and degradation properties of biodegradable polymers have made them attractive materials for biomedical applications. This review summarises the advances in drug delivery systems, specifically design of nanoparticles based on the biodegradable polymers. We also discuss the research performed in the area of biophotonics and challenges and opportunities brought by the design and application of biodegradable polymers in tissue engineering. We then discuss state-of-the-art research in the design and application of biodegradable polymers in packaging and emphasise the advances in smart packaging development. Finally, we provide an overview of the biodegradation of these polymers and composites in managed and unmanaged environments.

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Section: Bioplastics Polymers As Implants In Vivomentioning

confidence: 99%

Recent Advances in Bioplastics: Application and Biodegradation

et al. 2020

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“…At the same time, the formulation of polynucleotides within nanosystems is able to protect them from degradation (45). Bearing all this in mind, we have formulated poly(I:C) in the form of nanocomplexes enveloped with two biodegradable and stabilizing polymers (PEG-PGA and HA), known to facilitate the arrival to the tumor site (40,(46)(47)(48)(49)(50)(51)(52)(53). Once in the tumor, a preferential uptake of the nanosystems by macrophages could be anticipated due to their high phagocytic capacity, as already described for both, targeted and non-targeted nanosystems (15,54,55).…”

Section: Design and Development Of Poly(i:c) Nanocomplexesmentioning

confidence: 99%

“…The presence of PEG as the external layer of the system was intended to provide steric protection and increase its colloidal stability (62). Additionally, the combination of PEG and PGA as the outer layer of polymeric nanocapsules has already been shown to facilitate their access to the tumor site in a passive manner (46,47), and to improve the stability of C12r8-based nanocomplexes in biologically relevant media (61,63).…”

Section: Peg-pga-enveloped Nanocomplexesmentioning

confidence: 99%

Arginine-Based Poly(I:C)-Loaded Nanocomplexes for the Polarization of Macrophages Toward M1-Antitumoral Effectors

et al. 2020

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Tumor-associated macrophages (TAMs), with M2-like immunosuppressive profiles, are key players in the development and dissemination of tumors. Hence, the induction of M1 pro-inflammatory and anti-tumoral states is critical to fight against cancer cells. The activation of the endosomal toll-like receptor 3 by its agonist poly(I:C) has shown to efficiently drive this polarization process. Unfortunately, poly(I:C) presents significant systemic toxicity, and its clinical use is restricted to a local administration. Therefore, the objective of this work has been to facilitate the delivery of poly(I:C) to macrophages through the use of nanotechnology, that will ultimately drive their phenotype toward pro-inflammatory states. Methods: Poly(I:C) was complexed to arginine-rich polypeptides, and then further enveloped with an anionic polymeric layer either by film hydration or incubation. Physicochemical characterization of the nanocomplexes was conducted by dynamic light scattering and transmission electron microscopy, and poly(I:C) association efficiency by gel electrophoresis. Primary human-derived macrophages were used as relevant in vitro cell model. Alamar Blue assay, ELISA, PCR and flow cytometry were used to determine macrophage viability, polarization, chemokine secretion and uptake of nanocomplexes. The cytotoxic activity of pre-treated macrophages against PANC-1 cancer cells was assessed by flow cytometry. Results: The final poly(I:C) nanocomplexes presented sizes lower than 200 nm, with surface charges ranging from +40 to −20 mV, depending on the envelopment. They all presented high poly(I:C) loading values, from 12 to 50%, and great stability in cell culture media. In vitro, poly(I:C) nanocomplexes were highly taken up by macrophages, in comparison to the free molecule. Macrophage treatment with these nanocomplexes did not reduce their viability and efficiently stimulated the secretion of the T-cell recruiter chemokines CXCL10 and CCL5, of great importance for an effective anti-tumor immune response. Finally, poly(I:C) nanocomplexes significantly increased the ability of treated macrophages to directly kill cancer cells. Dacoba et al. Poly(I:C) Nanocomplexes for Macrophage M1-Polarization Conclusion: Overall, these enveloped poly(I:C) nanocomplexes might represent a therapeutic option to fight cancer through the induction of cytotoxic M1-polarized macrophages.

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“…Antibodies (13,42,43) exhibited the highest percentage of distributions lying within twofold error, followed by metal (37,(44)(45)(46), polymer (47)(48)(49)(50), and QD-based (51-54) NMs (Fig. 5E).…”

Section: Tissue-level Uptake Of Nms Can Be Predicted For Multiple Spementioning

confidence: 99%

Animal simulations facilitate smart drug design through prediction of nanomaterial transport to individual tissue cells

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2020

Sci. Adv.

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Smart drug design for antibody and nanomaterial-based therapies allows optimization of drug efficacy and more efficient early-stage preclinical trials. The ideal drug must display maximum efficacy at target tissue sites, with transport from tissue vasculature to the cellular environment being critical. Biological simulations, when coupled with in vitro approaches, can predict this exposure in a rapid and efficient manner. As a result, it becomes possible to predict drug biodistribution within single cells of live animal tissue without the need for animal studies. Here, we successfully utilized an in vitro assay and a computational fluid dynamic model to translate in vitro cell kinetics (accounting for cell-induced degradation) to whole-body simulations for multiple species as well as nanomaterial types to predict drug distribution into individual tissue cells. We expect this work to assist in refining, reducing, and replacing animal testing, while providing scientists with a new perspective during the drug development process.

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Biodistribution of radiolabeled polyglutamic acid and PEG-polyglutamic acid nanocapsules

Cited by 18 publications

References 34 publications

Recent Advances in Bioplastics: Application and Biodegradation

Recent Advances in Bioplastics: Application and Biodegradation

Arginine-Based Poly(I:C)-Loaded Nanocomplexes for the Polarization of Macrophages Toward M1-Antitumoral Effectors

Animal simulations facilitate smart drug design through prediction of nanomaterial transport to individual tissue cells

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