LINA BADDIA MOHAMED
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Resumo IPEN-doc 23057 State of the art and current advances on protein cross-linking by irradiation: protein based nanocarriers and bioactive nanoparticles2017 - VARCA, G.H.C.; MOHAMED, L.B.; FAZOLIN, G.N.; BATISTA, J.G.D.S.; QUEIROZ, R.G.; LUGAO, A.B.; NAVARRO MARQUES, F.A.; FERREIRA, A.H.The highlighted role of protein and peptide based delivery systems relies upon the possibility to develop biocompatible drug carriers featuring site specific delivery, biological affinity among unique advantages. Recently, a technique for protein nanostructuring by the use of radiation has been recently reported by our group. Advantages of the use of radiation over conventional methods are related to the possibility to achieve protein cross-linking and sterilization in a single step, as well as the capacity to allow the design of nanocarriers without the need of monomers or toxic cross-linkers. This work reports the use of high energy irradiation towards the design of size-controlled protein-based nanocarriers and bioactive nanoparticles, using bovine serum albumin (BSA) and papain as model protein and protease, respectively, including the state of the art and current advances of the technology. The technique implies on protein desolvation/solvation techniques followed by cross-linking by EB radiation or -irradiation alone, although nanoparticles were also achieved in absence of the cosolvents. Size-controlled BSA nanocarriers were manufactured up to 80 nm and papain bioactive nanoparticles up to 12 nm, as determined by dynamic light scattering. Nanocarrier morphology was evaluated by and negative staining transmission electron microscopy. Protein cross-linking and changes in aromatic the amino acids were evaluated by fluorescence measurements. Biocompatibility experimentswere also performed by means of cytotoxicity and cytokines production. The potential of the systems for the delivery of radiopharmaceuticals or chemotherapeutic agents were also assayed, using technetium or Paclitaxel respectively. In conclusion, the technique allowed the production of biocompatible and bioactive protein nanoparticles suitable for the administration of radiopharmaceuticals and chemotherapeutic agents.Resumo IPEN-doc 23777 Engineered papain nanoparticles by gamma irradiation: towards safe therapeutic applications2016 - VARCA, GUSTAVO; LIMA, MAYARA I.S.; ALVES, PATRICIA T.; MOHAMED, LINA B.; GRASSELLI, MARIANO; GOULART, LUIZ R.; LUGAO, ADEMAR B.This article provides an in vitro biological approach of the so called radiation synthesized protein-based nanoparticles as the use of nanoparticles for biomedical purposes requires precise understanding of their properties and effects on the body before clinical may take place. This technique allows proper control of papain nanoparticles with preserved biological activity for drug delivery. Biocompatibility results revealed that papain nanoparticles, of approximately 8-9 nm, were found to be biosafe in PBMC cells at concentrations up to 0.4 mg.ml-1 for up to 72 hours period. The nanoparticles were able to specifically bind to anti-Carica papaya polyclonal antibody with higher intensity than native papain. The stimuli of mouse splenocytes by papain nanoparticles led to the production of high levels of IL2. No significant levels of IL6, IL10 and IFNγ were produced by the stimuli. At nanoparticle concentrations above the cytotoxic limit, the concentration of IL2 was totally suppressed indicating no pro- nor anti-inflammatory response by means of cytokine mediated pathways. These in vitro results suggest that papain nanoparticles crosslinked by gamma irradiation may be safely administered with low nor negligible toxicity, holding strong applications for drug loading.Resumo IPEN-doc 23778 Protein crosslinking by high energy irradiation - towards the development of size-controlled biocompatible nanocarriers2016 - VARCA, G.H.; MOHAMED, L.B.; FAZOLIN, G.N.; OLIVEIRA, J.P.; BATISTA, J.G.; LUGAO, A.B.Protein and peptide based delivery systems are on the spotlight considering their unique properties specially related to site specific delivery and high biocompatibility despite other biopharmaceutical advantages. Following the recent success of the so-called NAB platform, most of the attention has been driven towards the development of cosolvent -free or crosslinker-free technologies capable of producing protein nanoparticles with a specific size or shape, in the seek for better or preferential tumor uptake and low or negligible toxicity among other features. Within this context irradiation stands a tool capable of promoting protein crosslinking and sterilization of the systems simultaneously, in which combined or not with other techniques may allow the design of nanocarriers without the need of monomers or toxic crosslinkers. This research details the use of high energy irradiation towards the design of size-controlled protein-based nanocarriers for drug delivery. The albumin or papain based nanocarriers were designed by combining desolvation/solvation techniques followed by gamma irradiation or gamma irradiation alone. Sizecontrolled nanocarriers were manufactured up to 80 nm, as determined by dynamic light scattering, depending upon the protein or the presence of cosolvent. Nanocarrier morphology was evaluated by transmission electron microscopy, and protein crosslinking was evaluated by means of bityrosine formation using fluorescence measurements. Final applications of the developed systems comprise relevant potential for the delivery of radiopharmaceuticals or chemotherapic agents.