Madeira Chemistry Research Centre

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Publications

Physicochemical properties and cell viability of shrimp chitosan films as affected by film casting solvents. I-potential use as wound dressing

Publication . 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.

2020Journal article

Open access

Engineered Neutral Phosphorous Dendrimers Protect Mouse Cortical Neurons and Brain Organoids from Excitotoxic Death

Publication . Posadas, Inmaculada; Romero-Castillo, Laura; Ronca, Rosa-Anna; Karpus, Andrii; Mignani, Serge; Majoral, Jean-Pierre; Muñoz-Fernández, Mariángeles; Ceña, Valentin

Nanoparticles are playing an increasing role in biomedical applications. Excitotoxicity plays a significant role in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s or Parkinson’s disease. Glutamate ionotropic receptors, mainly those activated by N-methyl-D aspartate (NMDA), play a key role in excitotoxic death by increasing intraneuronal calcium levels; triggering mitochondrial potential collapse; increasing free radicals; activating caspases 3, 9, and 12; and inducing endoplasmic reticulum stress. Neutral phosphorous dendrimers, acting intracellularly, have neuroprotective actions by interfering with NMDA-mediated excitotoxic mechanisms in rat cortical neurons. In addition, phosphorous dendrimers can access neurons inside human brain organoids, complex tridimensional structures that replicate a significant number of properties of the human brain, to interfere with NMDA-induced mechanisms of neuronal death. Phosphorous dendrimers are one of the few nanoparticles able to gain access to the inside of neurons, both in primary cultures and in brain organoids, and to exert pharmacological actions by themselves.

2022Journal article

Open access

Functionalized Nitroimidazole Scaffold Construction and Their Pharmaceutical Applications: A 1950–2021 Comprehensive Overview

Publication . Gupta, Ria; Sharma, Sumit; Singh, Rohit; Vishwakarma, Ram A.; Mignani, Serge; Singh, Parvinder Pal

Nitroimidazole represents one of the most essential and unique scaffolds in drug discovery since its discovery in the 1950s. It was K. Maeda in Japan who reported in 1953 the first nitroimidazole as a natural product from Nocardia mesenterica with antibacterial activity, which was later identified as Azomycin 1 (2-nitroimidazole) and remained in focus until now. This natural antibiotic was the starting point for synthesizing numerous analogs and regio-isomers, leading to several life-saving drugs and clinical candidates against a number of diseases, including infections (bacterial, viral, parasitic) and cancers, as well as imaging agents in medicine/diagnosis. In the present decade, the nitroimidazole scaffold has again been given two life-saving drugs (Delamanid and Pretomanid) used to treat MDR (multi-drug resistant) tuberculosis. Keeping in view the highly successful track-record of the nitroimidazole scaffold in providing breakthrough therapeutic drugs, this comprehensive review focuses explicitly on presenting the activity profile and synthetic chemistry of functionalized nitroimidazole (2-, 4- and 5-nitroimidazoles as well as the fused nitroimidazoles) based drugs and leads published from 1950 to 2021. The present review also presents the miscellaneous examples in each class. In addition, the mutagenic profile of nitroimidazole-based drugs and leads and derivatives is also discussed.

2022Journal article

Open access

Phosphorus dendron nanomicelles as a platform for combination anti-inflammatory and antioxidative therapy of acute lung injury

Publication . Li, Jin; Chen, Liang; Li, Changsheng; Fan, Yu; Zhan, Mengsi; Sun, Huxiao; Mignani, Serge; Majoral, Jean-Pierre; Shen, Mingwu; Shi, Xiangyang

Rationale: Development of novel nanomedicines to inhibit pro-inflammatory cytokine expression and reactive oxygen species (ROS) generation for anti-inflammatory therapy of acute lung injury (ALI) remains challenging. Here, we present a new nanomedicine platform based on tyramine-bearing two dimethylphosphonate sodium salt (TBP)-modified amphiphilic phosphorus dendron (C11G3) nanomicelles encapsulated with antioxidant drug curcumin (Cur). Methods: C11G3-TBP dendrons were synthesized via divergent synthesis and self-assembled to generate nanomicelles in a water environment to load hydrophobic drug Cur. The created C11G3-TBP@Cur nanomicelles were well characterized and systematically examined in their cytotoxicity, cellular uptake, intracellular ROS elimination, pro-inflammatory cytokine inhibition and alveolar macrophages M2 type repolarization in vitro, and evaluated to assay their anti-inflammatory and antioxidative therapy effects of ALI mice model through pro-inflammatory cytokine expression level in bronchoalveolar lavage fluid and lung tissue, histological analysis and micro-CT imaging detection of lung tissue injury in vivo. Results: The nanomicelles with rigid phosphorous dendron structure enable high-capacity and stable Cur loading. Very strikingly, the drug-free C11G3-TBP micelles exhibit excellent cytocompatibility and intrinsic anti-inflammatory activity through inhibition of nuclear transcription factor-kappa B, thus causing repolarization of alveolar macrophages from M1 type to anti-inflammatory M2 type. Taken together with the strong ROS scavenging property of the encapsulated Cur, the developed nanomicelles enable effective therapy of inflammatory alveolar macrophages in vitro and an ALI mouse model in vivo after atomization administration. Conclusion: The created phosphorus dendron nanomicelles can be developed as a general nanomedicine platform for combination anti-inflammatory and antioxidative therapy of inflammatory diseases.

2022Journal article

Open access

Tangerines cultivated on Madeira Island: a high throughput natural source of bioactive compounds

Publication . Figueira, José A.; Porto-Figueira, Priscilla; Pereira, Jorge A. M.; Câmara, José S.

Tangerines (Citrus reticulata) are popular fruits worldwide, being rich in many bioactive metabolites. The setubalense variety cultivated on Madeira Island has an intense aroma easily distinguishable from other tangerines, being traditionally used to enrich several foods and beverages. Nonetheless, setubalense volatile composition has never been characterized, and we aimed to unveil the bioactive potential of peels and juices of setubalense tangerines and compare them with the murcott variety grown in Portugal mainland. Using headspace solid-phase microextraction coupled to gas chromatography mass spectrometry (HS-SPME/GC-MS), we identified a total of 128 volatile organic metabolites (VOMs) in the juice and peels, with d-limonene, γ-terpinene, β-myrcene, α- and β-pinene, o-cymene, and terpinolene, the most dominant in both cultivars. In contrast, setubalense juices are richer in terpenes, many of them associated with health protection. Discriminant analysis revealed a pool of VOMs, including β-caryophyllene and E-ocimene, with bioactive properties able to differentiate among tangerines according to variety and sample type (peel vs. juice). This is the first report on the volatile composition of setubalense tangerines grown on Madeira Island revealing that its pungent aroma is constituted by secondary metabolites with specific aroma notes and health properties. This is strong evidence of the higher nutraceutical value of such fruit for the human diet.

2020Journal article

Open access