In this paper we describe the biodistribution of doxorubicin (DXR) encapsulated in three different types of liposomes. Common composition was hydrogenated phosphatidylcholine (HPC)/phosphatidylglycerol (PG) cholesterol (Chol)/X, X being either 10% N-glutaryl phosphatidylethanolamine (NGPE), 10% NGPE + 6% distearoyl-phosphatidylethanolamine-polyethyleneglycol 2000 (DSPE-PEG), or 10% NGPE + 6% DSPE-PEG-COOH. These series of vesicles were coated with an active or an inactive sequence of laminin (laminin receptors, integrins, are overexpressed in tumor cells). Single doses of these preparations were injected, i.v., into healthy mice. For biodistribution experiments, mice were sacrificed at three different time-points post-treatment. Doxorubicin and doxorubicinol (DXOH) levels were determined in plasma, heart, lung, kidney, spleen, and liver using HPLC with daunorubicin (DNR) as internal standard. The results obtained indicate that compositions containing DSPE-PEG have the longest half-lives in plasma, as was to be expected according to the data in the literature. However, the presence of the peptides on the surface of liposomes reduces concentration values in this tissue. Distribution in other organs reveals high differences, among the liposomal samples studied, depending mainly on the presence of active or inactive peptide on the surface of vesicles. Liposomes coated with the laminin active sequence show lower accumulation in studied tissues than free DXR. This indicates that heart toxicity, associated to DXR treatments, could be diminished, and open promising perspectives for its future study in tumor-bearing animals.
Three-dimensional engineering of skeletal muscle is becoming increasingly relevant for tissue engineering, disease modeling and bio-hybrid robotics, where flexible, versatile and multidisciplinary approaches for the evaluation of tissue differentiation, functionality and force measurement are required. This works presents a 3D-printed platform of bioengineered human skeletal muscle which can efficiently model the three-dimensional structure of native tissue, while providing information about force generation and contraction profiles. Proper differentiation and maturation of myocytes is demonstrated by the expression of key myo-proteins using immunocytochemistry and analyzed by confocal microscopy, and the functionality assessed via electrical stimulation and analysis of contraction kinetics. To validate the flexibility of this platform for complex tissue modelling, the bioengineered muscle is treated with tumor necrosis factor α to mimic the conditions of aged or senescence-like tissue, which is supported by morphological and functional changes. Moreover, as a proof of concept, the effects of Argireline ® Amplified peptide, a cosmetic ingredient that causes muscle relaxation, are evaluated in both healthy and aged tissue models. Therefore, the results demonstrate that this 3D-bioengineered human muscle platform could be used to assess morphological and functional changes in the aging process of muscular tissue with potential applications in biomedicine, cosmetics and bio-hybrid robotics.
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