The chorioallantoic membrane as a bio-barrier model for the evaluation of nanoscale drug delivery systems for tumour therapy

Preis, Eduard; Schulze, Jan; Gutberlet, Bernd; Pinnapireddy, Shashank Reddy; Jedelská, Jarmila; Bakowsky, Udo

doi:10.1016/j.addr.2021.04.022

Cited by 19 publications

(16 citation statements)

References 195 publications

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“…In laboratory animal studies, 3R principles, 7 which guide the ethical handling of laboratory animals, should be followed. This may be achieved by refining the procedures in favor of animal welfare, 8 reducing the number of animals needed, 9 and replacing animal models 10 . Partial bile duct ligation (PBDL) is favorable not only to the 3R principles by keeping the liver function intact to decrease morbidity and mortality, 6 but also the internal comparisons between the ligated and non‐ligated lobes, which are subjected to the same systemic effects, such as the biological internal environment.…”

mentioning

confidence: 99%

Characterizing Fibrosis and Inflammation in a Partial Bile Duct Ligation Mouse Model by Multiparametric Magnetic Resonance Imaging

Liu

Cai

Ding

et al. 2021

Magnetic Resonance Imaging

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Background Partial bile duct ligation (PBDL) model is a reliable cholestatic fibrosis experimental model that showed complex histopathological changes. Magnetic resonance imaging (MRI) features of PBDL have not been well characterized. Purpose To investigate the potential of MRI parameters in assessing fibrosis in PBDL and explore the relationships between MRI and pathological features. Animal Model Established PBDL models. Population Fifty‐four mice were randomly divided into four timepoints PBDL groups and one sham group. Field Strength/Sequence 3.0 T; MRI sequences included T1‐weighted fast spin‐echo (FSE), T2‐weighted single shot FSE, variable flip angle T1 mapping, multi‐echo SE T2 mapping, multi‐echo gradient‐echo T2* mapping, and multi‐b‐value diffusion‐weighted imaging. Assessment MRI examination was performed at the corresponding timepoints after surgery. Native T1, ΔT1 (T1native‐T1post), T2, T2*, apparent diffusion coefficient (ADC) values, histogram parameters (skewness and kurtosis), intravoxel incoherent motion parameters (f, D, and D*) within the entire ligated (PBDL), non‐ligated liver (PBDL), and whole liver (sham) were obtained. Fibrosis and inflammation were assessed in Masson and H&E staining slices using the Metavir and activity scoring system. Statistical Tests One‐way ANOVA, Spearman's rank correlation, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. Results Fibrosis and inflammation were finally staged as F3 and A3 in ligated livers but were not observed in non‐ligated or sham livers. Ligated livers displayed significantly elevated native T1, ΔT1, T2, and reduced ADC and T2* than other livers. Spearman's correlation showed better correlation with inflammation (r = 0.809) than fibrosis (r = 0.635) in T2 and both ΔT1 and ADC showed stronger correlation with fibrosis (r = 0.704 and r = −0.718) than inflammation (r = 0.564 and r = −0.550). Area under the curve (AUC) for ΔT1 performed the highest (0.896). When combined with all relative parameters, AUC increased to 0.956. Data Conclusion Multiparametric MRI can evaluate and differentiate pathological changes in PBDL. ΔT1 and ADC better correlated with fibrosis while T2 stronger with inflammation. Level of Evidence 1 Technical Efficacy Stage 2

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confidence: 99%

Characterizing Fibrosis and Inflammation in a Partial Bile Duct Ligation Mouse Model by Multiparametric Magnetic Resonance Imaging

Liu

Cai

Ding

et al. 2021

Magnetic Resonance Imaging

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“…The chorioallantoic membrane (CAM) of fertilized hen's eggs has been successfully used as a substrate for tumor xenografts for more than a century. 1 Furthermore, the CAM model can be used for three-dimensional cell culture and for evaluation of different therapeutic options in case of successful standardized xenografting. In particular, through the efforts of the 3Rs principle (replacement, reduction, and refinement) to protect higher animals used for scientific purposes such as rabbits, mice, or rats, the CAM model is gaining the attention it deserves.…”

Section: Introductionmentioning

confidence: 99%

How to Xenograft Cancer Cells on the Chorioallantoic Membrane of a Fertilized Hen’s Egg and Its Visualization by PET/CT and MRI

Schulze

Librizzi²,

Bender

et al. 2023

ACS Appl. Bio Mater.

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The chorioallantoic membrane (CAM) of fertilized hen's eggs represents a unique and alternative model for cancer research. The CAM model provides an optimal platform for xenografting cancer cell lines and studying essential key factors. Tumor size and growth as well as angiogenesis can be investigated to evaluate the response of therapies and strategies against cancer. Preclinical imaging represented by magnetic resonance imaging and positron emission tomography/computed tomography can generate detailed anatomical and functional information and reveal excellent metabolic sensitivity. In the following, a guideline is introduced in order to find a simplified entrance to the CAM model in combination with modern preclinical imaging techniques. Finally, the presented procedures are additionally completed by histological studies in the form of hematoxylin and eosin as well as immunohistochemical staining.

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“…Over the past decades, many advantages of conventional liposomes have been revealed, e.g., high versatility, good biocompatibility, and prolonged drug half-life, emphasizing their suitability as a tailor-made drug delivery system [ 3 , 4 , 5 , 6 , 7 , 8 ]. Biocompatible properties allow them to be used as delivery systems for drugs, proteins, plasmid DNAs, antisense oligonucleotides, or ribosomes, as well as for biochemical, pharmaceutical, and cosmetic purposes [ 9 , 10 , 11 , 12 ]. Besides the non-pathogenic and non-immunogenic features, their production is of relatively low cost.…”

Section: Introductionmentioning

confidence: 99%

Highly Stable Liposomes Based on Tetraether Lipids as a Promising and Versatile Drug Delivery System

et al. 2022

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Conventional liposomes often lack stability, limiting their applicability and usage apart from intravenous routes. Nevertheless, their advantages in drug encapsulation and physicochemical properties might be helpful in oral and pulmonary drug delivery. This study investigated the feasibility and stability of liposomes containing tetraether lipids (TEL) from Thermoplasma acidophilum. Liposomes composed of different molar ratios of TEL:Phospholipon 100H (Ph) were produced and exposed to various temperature and pH conditions. The effects on size, polydispersity index, and zeta potential were examined by dynamic and electrophoretic light scattering. Autoclaving, which was considered an additional process step after fabrication, could minimize contamination and prolong shelf life, and the stability after autoclaving was tested. Moreover, 5(6)-carboxyfluorescein leakage was measured after incubation in the presence of fetal calf serum (FCS) and lung surfactant (Alveofact). The incorporation of TEL into the liposomes significantly impacted the stability against low pH, higher temperatures, and even sterilization by autoclaving. The stability of liposomes containing TEL was confirmed by atomic force microscopy as images revealed similar sizes and morphology before and after incubation with FCS. It could be concluded that increasing the molar ratio in the TEL:Ph liposome formulations improved the structural stability against high temperature, low pH, sterilization via autoclaving, and the presence of FCS and lung surfactant.

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The chorioallantoic membrane as a bio-barrier model for the evaluation of nanoscale drug delivery systems for tumour therapy

Cited by 19 publications

References 195 publications

Characterizing Fibrosis and Inflammation in a Partial Bile Duct Ligation Mouse Model by Multiparametric Magnetic Resonance Imaging

Characterizing Fibrosis and Inflammation in a Partial Bile Duct Ligation Mouse Model by Multiparametric Magnetic Resonance Imaging

How to Xenograft Cancer Cells on the Chorioallantoic Membrane of a Fertilized Hen’s Egg and Its Visualization by PET/CT and MRI

Highly Stable Liposomes Based on Tetraether Lipids as a Promising and Versatile Drug Delivery System

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