GUSTAVO HENRIQUE COSTAVARCA
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Artigo IPEN-doc 29706 Mucoadhesive gellan gum-based and carboxymethyl cellulose -based hydrogels containing gemcitabine and papain for bladder cancer treatment2023 - LIMA, CAROLINE S.A. de; RIAL-HERMIDA, MARIA I.; FREITAS, LUCAS F. de; PEREIRA-DA-MOTA, ANA F.; VIVERO-LOPEZ, MARIA; FERREIRA, ARYEL H.; KADŁUBOWSKI, SŁAWOMIR; VARCA, GUSTAVO H.C.; LUGAO, ADEMAR B.; ALVAREZ-LORENZO, CARMENLocal treatment of bladder cancer faces several limitations such as short residence time or low permeation through urothelium tissue. The aim of this work was to develop patient-friendly mucoadhesive gel formulations combining gemcitabine and the enzyme papain for improved intravesical chemotherapy delivery. Hydrogels based on two different polysaccharides, gellan gum and sodium carboxymethylcellulose (CMC), were prepared with either native papain or papain nanoparticles (nanopapain) to explore for the first time their use as permeability enhancers through bladder tissue. Gel formulations were characterized regarding enzyme stability, rheological behavior, retention on bladder tissue and bioadhesion, drug release properties, permeation capacity, and biocompatibility. After 90 days of storage, the enzyme loaded in the CMC gels retained up to 83.5 ± 4.9 % of its activity in the absence of the drug, and up to 78.1 ± 5.3 with gemcitabine. The gels were mucoadhesive and the enzyme papain showed mucolytic action, which resulted in resistance against washing off from the urothelium and enhanced permeability of gemcitabine in the ex vivo tissue diffusion tests. Native papain shortened lag-time tissue penetration to 0.6 h and enhanced 2-fold drug permeability All formulations demonstrated pseudoplastic behavior and no irritability. Overall, the developed formulations have potential as an upgraded alternative to intravesical therapy for bladder cancer treatment.Artigo IPEN-doc 22652 Synthesis of papain nanoparticles by electron beam irradiation – A pathway for controlled enzyme crosslinking2016 - VARCA, G.H.C.; KADLUBOWSKI, S.; WOLSZCZAK, M.; LUGAO, A.B.; ROSIAK, J.M.; ULANSKI, P.Crosslinked enzyme aggregates comprise more stable and highly concentrated enzymatic preparationsof current biotechnological and biomedical relevance. This work reports the development of crosslinkednanosized papain aggregates using electron beam irradiation as an alternative route for controlledenzyme crosslinking. The nanoparticles were synthesized in phosphate buffer using various ethanol con-centrations and electron beam irradiation doses. Particle size increase was monitored using dynamiclight scattering. The crosslinking formation by means of bityrosine linkages were measured by fluores-cence spectra and the enzymatic activity was monitored using Na-Benzoyl-dl-arginine p-nitroanilidehydrochloride as a substrate. The process led to crosslinked papain nanoparticles with controlled sizesranging from 6 to 11 nm depending upon the dose and ethanol concentration. The irradiation atmosphereplayed an important role in the final bioactivity of the nanoparticles, whereas argon and nitrous oxidesaturated systems were more effective than at atmospheric conditions in terms of preserving papain enzy-matic activity. Highlighted advantages of the technique include the lack of monomers and crosslinkingagents, quick processing with reduced bioactivity changes, and the possibility to be performed inside thefinal package simultaneously with sterilization.