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- Physicochemical properties and cell viability of shrimp chitosan films as affected by film casting solvents. I-potential use as wound dressingPublication . Eulálio, Hugo Yves C.; Vieira, Mariana; Fideles, Thiago B.; Tomás, Helena; Silva, Suédina M. L.; Peniche, Carlos A.; Fook, Marcus Vinícius L.: Chitosan solubility in aqueous organic acids has been widely investigated. However, most of the previous works have been done with plasticized chitosan films and using acetic acid as the film casting solvent. In addition, the properties of these films varied among studies, since they are influenced by different factors such as the chitin source used to produce chitosan, the processing variables involved in the conversion of chitin into chitosan, chitosan properties, types of acids used to dissolve chitosan, types and amounts of plasticizers and the film preparation method. Therefore, this work aimed to prepare chitosan films by the solvent casting method, using chitosan derived from Litopenaeus vannamei shrimp shell waste, and five different organic acids (acetic, lactic, maleic, tartaric, and citric acids) without plasticizer, in order to evaluate the effect of organic acid type and chitosan source on physicochemical properties, degradation and cytotoxicity of these chitosan films. The goal was to select the best suited casting solvent to develop wound dressing from shrimp chitosan films. Shrimp chitosan films were analyzed in terms of their qualitative assessment, thickness, water vapor permeability (WVP), water vapor transmission rate (WVTR), wettability, tensile properties, degradation in phosphate buffered saline (PBS) and cytotoxicity towards human fibroblasts using the resazurin reduction method. Regardless of the acid type employed in film preparation, all films were transparent and slightly yellowish, presented homogeneous surfaces, and the thickness was compatible with the epidermis thickness. However, only the ones prepared with maleic acid presented adequate characteristics of WVP, WVTR, wettability, degradability, cytotoxicity and good tensile properties for future application as a wound dressing material. The findings of this study contributed not only to select the best suited casting solvent to develop chitosan films for wound dressing but also to normalize a solubilization protocol for chitosan, derived from Litopenaeus vannamei shrimp shell waste, which can be used in the pharmaceutical industry.
- Self‐assembly of cholesterol‐Doxorubicin and TPGS into Prodrug‐based nanoparticles with enhanced cellular uptake and Lysosome‐dependent pathway in breast cancer cellsPublication . Olim, Filipe; Neves, Ana Rute; Vieira, Mariana; Tomás, Helena; Sheng, RuilongDeveloping new easy-to-prepare functional drug delivery nanosystems with good storage stability, low hemotoxicity, as well as controllable drug delivery property, has attracted great attention in recent years. In this work, a cholesterol-based prodrug nanodelivery system is prepared by self-assembly of cholesterol-doxorubicin prodrug conjugates (Chol-Dox) and tocopherol polyethylene glycol succinate (TPGS) using thin-film hydration method. The Chol-Dox/TPGS assemblies (molar ratio 2:1, 1:1, and 1:2) are able to form nanoparticles with average hydrodynamic diameter of ≈140–214 nm, surface zeta potentials of ≈−24.2–−0.3 mV, and remarkable solution stability in 0.1 m PBS, 16 days). The Chol-Dox/TPGS assemblies show low hemotoxicity and different cytotoxicity profiles in breast cancer cells (MCF-7 and MDA-MB-231), which are largely dependent on the molar ratio of Chol-Dox and TPGS. The Chol-Dox/TPGS assemblies tend to enter into MCF-7 and MDA-MB-231 cells through non-Clathrin-mediated multiple endocytosis and lysosome-dependent uptake pathways, moreover, these nanoassemblies demonstrate lysosome-dependent intracellular localization, which is different from that of free DOX (nuclear localization). The results demonstrate that the Chol-Dox/TPGS assemblies are promising cholesterol-based prodrug nanomaterials for breast cancer chemotherapy. Practical Applications: This work demonstrates a lipid prodrug-based nanotherapeutic system. Herein the Chol-Dox/TPGS nanoassemblies could serve as promising and controllable cholesterol-based prodrug nanomaterials/nano-formulations for potential breast cancer chemotherapy.