Post-insertion parameters of PEG-derivatives in phosphocholine-liposomes

Mare, Rosario; Paolino, Donatella; Celia, Christian; Molinaro, Roberto; Fresta, Massimo; Cosco, Donato

doi:10.1016/j.ijpharm.2018.10.028

Cited by 35 publications

(24 citation statements)

References 44 publications

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“…In order to overcome these drawbacks, the current approach is PEGylation [ 2 ] that consists of direct and/or linked polyethylene glycol (PEG) conjugation to therapeutics. Since its introduction in the 1970s, PEG has largely impacted the pharmaceutical field, and 16 PEGylated products are currently present in the market, [ 3 ] as reported in Table 1 .…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of Polyethylene Glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach

d’Avanzo

Celia

Barone

et al. 2020

Advanced Therapeutics

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PEGylation technique is currently considered the gold standard approach to provide a long and safe circulation of drugs. Although this is the accepted dogma, various clinical reports and animal studies show the occurrence of immunogenic responses against polyethylene glycol (PEG) after systemic injection. These side effects, associated with complement activation and/or anti‐PEG antibody production, result in hypersensitivity reactions and lack of therapeutic efficacy of the drug during clinical protocols. Furthermore, different healthy patients show the presence of anti‐PEG antibodies in their blood stream, even though they have not received PEGylated drugs. The aim of this review is to discuss the main mechanisms based on PEG immunogenicity and its clinical implications and report the most promising approaches to reduce these unexpected side effects.

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Section: Introductionmentioning

confidence: 99%

Immunogenicity of Polyethylene Glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach

d’Avanzo

Celia

Barone

et al. 2020

Advanced Therapeutics

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“…mApoE peptide was covalently attached on LIP surface by thiol-maleimide coupling, as previously described (Re et al, 2010(Re et al, , 2011. ClTx-lipid was added to mApoE-LIP by post-insertion technique, following the procedure previously described (Mare et al, 2018). This sample will be referred as Mf-LIP.…”

Section: Preparation Multifunctional Liposomesmentioning

confidence: 99%

Differential Exchange of Multifunctional Liposomes Between Glioblastoma Cells and Healthy Astrocytes via Tunneling Nanotubes

Formicola

D’Aloia

Magro

et al. 2019

Front. Bioeng. Biotechnol.

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Despite advances in cancer therapies, nanomedicine approaches including the treatment of glioblastoma (GBM), the most common, aggressive brain tumor, remains inefficient. These failures are likely attributable to the complex and not yet completely known biology of this tumor, which is responsible for its strong invasiveness, high degree of metastasis, high proliferation potential, and resistance to radiation and chemotherapy. The intimate connection through which the cells communicate between them plays an important role in these biological processes. In this scenario, tunneling nanotubes (TnTs) are recently gaining importance as a key feature in tumor progression and in particular in the re-growth of GBM after surgery. In this context, we firstly identified structural differences of TnTs formed by U87-MG cells, as model of GBM cells, in comparison with those formed by normal human astrocytes (NHA), used as a model of healthy cells. Successively, we have studied the possibility to exploit U87-MG TnTs as drug-delivery channels in cancer therapy, using liposomes composed of cholesterol/sphingomyelin and surface functionalized with mApoE and chlorotoxin peptides (Mf-LIP) as nanovehicle model. The results showed that U87-MG cells formed almost exclusively thick and long protrusions, whereas NHA formed more thin and short TnTs. Considering that thick TnTs are more efficient in transport of vesicles and organelles, we showed that fluorescent-labeled Mf-LIP can be transported via TnTs between U87-MG cells and with less extent through the protrusions formed by NHA cells. Our results demonstrate that nanotubes are potentially useful as drug-delivery channels for cancer therapy, facilitating the intercellular redistribution of this drug in close and far away cells, thus reaching isolated tumor niches that are hardly targeted by simple drug diffusion in the brain parenchyma. Moreover, the differences identified in TnTs formed by GBM and NHA cells can be exploited to increase treatment precision and specificity.

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“…Importantly, micellar and liposomal structures enable immune surveillance avoidance in blood, the strategic release of their cargoes, and extend circulating half-life [45]. In addition, inhibition of opsonization-induced complement activation can be enhanced by incorporating polyethylene glycol (PEG) into lipid carriers [47,48].…”

Section: Strategies For Prolonged Blood Circulationmentioning

confidence: 99%

“…Thus, lipid–PEG derivatives are widely utilized to protect drugs because of their convenience and functionalities [55]. Lipid–PEG derivatives are able to fuse with LBDDSs [48]. For example, polymeric micelles, mainly composed of lipid–PEG conjugates, reinforce in vivo applications, and have also been functionalized to improve pharmacological effects.…”

Section: Strategies For Prolonged Blood Circulationmentioning

confidence: 99%

A Promising Biocompatible Platform: Lipid-Based and Bio-Inspired Smart Drug Delivery Systems for Cancer Therapy

Kim

Kwon

Choi

et al. 2018

IJMS

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Designing new drug delivery systems (DDSs) for safer cancer therapy during pre-clinical and clinical applications still constitutes a considerable challenge, despite advances made in related fields. Lipid-based drug delivery systems (LBDDSs) have emerged as biocompatible candidates that overcome many biological obstacles. In particular, a combination of the merits of lipid carriers and functional polymers has maximized drug delivery efficiency. Functionalization of LBDDSs enables the accumulation of anti-cancer drugs at target destinations, which means they are more effective at controlled drug release in tumor microenvironments (TMEs). This review highlights the various types of ligands used to achieve tumor-specific delivery and discusses the strategies used to achieve the effective release of drugs in TMEs and not into healthy tissues. Moreover, innovative recent designs of LBDDSs are also described. These smart systems offer great potential for more advanced cancer therapies that address the challenges posed in this research area.

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Post-insertion parameters of PEG-derivatives in phosphocholine-liposomes

Cited by 35 publications

References 44 publications

Immunogenicity of Polyethylene Glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach

Immunogenicity of Polyethylene Glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach

Differential Exchange of Multifunctional Liposomes Between Glioblastoma Cells and Healthy Astrocytes via Tunneling Nanotubes

A Promising Biocompatible Platform: Lipid-Based and Bio-Inspired Smart Drug Delivery Systems for Cancer Therapy

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