115 research outputs found
Polymeric Hydrogels as Technology Platform for Drug Delivery Applications
Hydrogels have become key players in the field of drug delivery owing to their great versatility in terms of composition and adjustability to various administration routes, from parenteral (e.g., intravenous) to non-parenteral (e.g., oral, topical) ones. In addition, based on the envisioned application, the design of bioadhesive or mucoadhesive hydrogels with prolonged residence time in the administration site may be beneficial. For example, hydrogels are used as wound dressings and patches for local and systemic therapy. In a similar way, they can be applied in the vaginal tract for local treatment or in the nasal cavity for a similar goal or, conversely, to target the central nervous system by the nose-to-brain pathway. Overall, hydrogels have demonstrated outstanding capabilities to ensure patient compliance, while achieving long-term therapeutic effects. The present work overviews the most relevant and recent applications of hydrogels in drug delivery with special emphasis on mucosal routes.Fil: Sosnik, Alejandro Dario. Technion - Israel Institute of Technology; IsraelFil: Seremeta, Katia Pamela. Universidad Nacional del Chaco Austral. Departamento de Ciencias Básicas y Aplicadas. Laboratorio de Ingeniería de las Reacciones Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentin
Cryoprotection–lyophilization and physical stabilization of rifampicin-loaded flower-like polymeric micelles
Rifampicin-loaded poly(ε-caprolactone)-b-poly(ethylene glycol)-poly(ε-caprolactone) flower-like polymeric micelles display low aqueous physical stability over time and undergo substantial secondary aggregation. To improve their physical stability, the lyoprotection- lyophilization process was thoroughly characterized. The preliminary cryoprotectant performance of mono- and disaccharides (e.g. maltose, glucose), hydroxypropyl-β-cyclodextrin (HPβCD) and poly(ethylene glycol) (PEG) of different molecular weights was assessed in freeze-thawing assays at -20°C, -80°C and -196°C. The size and size distribution of the micelles at the different stages were measured by dynamic light scattering (DLS). A cryoprotectant factor (fc) was determined by taking the ratio between the size immediately after the addition of the cryoprotectant and the size after the preliminary freeze-thawing assay. The benefit of a synergistic cryoprotection by means of saccharide/ PEG mixtures was also assessed. Glucose (1 : 20), maltose (1 : 20), HPβCD (1 : 5) and glucose or maltose mixtures with PEG3350 (1 : 20) (copolymer:cryoprotectant weight ratio) were the most effective systems to protect 1 per cent micellar systems. Conversely, only HPβCD (1 : 5) cryoprotected more concentrated drug-loaded micelles (4% and 6%). Then, those micelle/ cryoprotectant systems that displayed fc values smaller than 2 were freeze-dried. The morphology of freeze-dried powders was characterized by scanning electron microscopy and atomic force microscopy and the residual water content analysed by the Karl Fisher method. The HPβCD-added lyophilisates were brittle porous cakes (residual water was between 0.8% and 3%), easily redispersable in water to form transparent systems with a minimal increase in the micellar size, as determined by DLS.Fil: Moretton, Marcela Analía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sosnik, Alejandro Dario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Chitosan-g-oligo(epsilon-caprolactone) polymeric micelles: microwave-assisted synthesis and physicochemical and cytocompatibility characterization
With the aim to produce mucoadhesive polymeric micelles for drug administration by mucosal routes, chitosan-g-oligo(epsilon-caprolactone) copolymers were synthesized by the microwave-assisted ring-opening polymerization of epsilon-caprolactone using chitosan as the macroinitiator and methanesulfonic acid as the solvent, catalyst and protecting group of the amine moieties. The reaction was conducted under very mild conditions and was completed within 10 min with a monomer conversion above 90%. The grafting of oligo(epsilon-caprolactone) blocks to the free hydroxyl groups of chitosan was confirmed by ATR/FT-IR, 1H- and 13C-NMR, WAXD and thermal analysis (TGA/DSC). The molecular weight of the synthetic hybrid copolymers was determined by GPC and MALDI-ToF mass spectrometry. Polymeric micelles obtained by the solvent diffusion/evaporation method showed a spherical shape (TEM and AFM) with sizes between 111 and 154 nm and highly positive zeta potential (>+50 mV) (DLS). In addition, they displayed good cell compatibility in the human lung adenocarcinoma epithelial line, A549, and were readily up-taken by the cervical cancer cell line, HeLa. Results from the encapsulation of the antituberculosis drug, rifampicin, showed that the micelles had better performance than other nanocarriers previously investigated (e.g., cyclodextrins). Moreover, the micelles conserved the mucoadhesiveness displayed by pristine chitosan and are expected to transiently open tight cell junctions and lead to more prolonged residence times in mucosal tissues and greater drug bioavailability.Fil: Glisoni, Romina Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Quintana Lazópulos, Silvina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Molina, María. Freie Universität Berlin; AlemaniaFil: Calderon, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Freie Universität Berlin; AlemaniaFil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Sosnik, Alejandro Dario. Technion - Israel Institute of Technology; Israel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Nanomedicine in Latin America
This special issue of Journal of Biomaterials and Tissue Engineering includes articles from Latin American researchers that work in an emerging discipline at the interface of biomaterials science, nanotechnology and therapeutics called Nanomedicine and that comprises the use of different mono, bi and three-dimensional nano-objects (e.g., nanoplates, nanoparticles, nanotubes, etc.) to address different medical problemsFil: Abraham, Gustavo Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Mar del Plata. Instituto de Investigación en Ciencia y Tecnología de Materiales (i); Argentina;Fil: Romero, Eder Lilia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Sosnik, Alejandro Dario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
High-grade extracellular vesicles preparation by combined size-exclusion and affinity chromatography
Extracellular vesicles (EVs) have recently gained growing interest for their diagnostic and therapeutic potential. Despite this, few protocols have been reported for the isolation of EVs with preserved biological function. Most EV purification methods include a precipitation step that results in aggregation of vesicles and most available techniques do not efficiently separate the various types of EVs such as exosomes and ectosomes, which are involved in distinct biological processes. For this reason, we developed a new two-step fast performance liquid chromatography (FPLC) protocol for purification of large numbers of EVs. The method comprises size exclusion chromatography followed by immobilized metal affinity chromatography, which is enabled by expression of poly-histidine tagged folate receptor α in the parental cells. Characterisation and comparison of the EVs obtained by this method to EVs purified by differential centrifugation, currently the most common method to isolate EVs, demonstrated higher purity and more selective enrichment of exosomes in EV preparations using our FPLC method, as assessed by comparison of marker proteins and density distribution. Our studies reveal new possibilities for the isolation of defined subpopulations of EVs with preserved biological function that can easily be upscaled for production of larger amounts of EVs
Transfer thermodynamics of triclosan from water to organic solvents with different hydrogen bonding capability
The thermodynamic functions Gibbs energy, enthalpy and entropy for the dissolution and mixing processes of triclosan (TS) in water are presented. These quantities were calculated by means of the van't Hoff and Gibbs equations from solubility values determined at temperatures ranging between 293.15 and 313.15 K. In addition, the corresponding thermodynamic quantities of the drug transfer processes from water to different organic solvents displaying different hydrogen bonding capability were also calculated. In all the evaluated cases, Gibbs energy of transfer comprised negative values, indicating the preference of TS for all the organic media evaluated. Nevertheless, enthalpy and entropy of transfer assumed positive or negative values according to every specific system. It was clear that hydrogen bonding plays a significant role in the dissolution and transfer processes of this antibacterial agent.Colegio de Farmacéuticos de la Provincia de Buenos Aire
Oral Pharmacokinetics of a Chitosan-Based Nano- Drug Delivery System of Interferon Alpha
Abstract: Interferon alpha (IFN) is a protein drug used to treat viral infections and cancer diseases. Dueto its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability,which is associated with severe side eects. We hypothesized that the nanoencapsulation ofIFN within nanoparticles of the mucoadhesive polysaccharide chitosan would improve theoral bioavailability of this drug. In this work, we produced IFN-loaded chitosan nanoparticlesby the ionotropic gelation method. Their hydrodynamic diameter, polydispersity index andconcentration were characterized by dynamic light scattering and nanoparticle tracking analysis.After confirming their good cell compatibility in Caco-2 and WISH cells, the permeability ofunmodified and poly(ethylene glycol) (PEG)-modified (PEGylated) nanoparticles was measured inmonoculture (Caco-2) and co-culture (Caco-2/HT29-MTX) cell monolayers. Results indicated thatthe nanoparticles cross the intestinal epithelium mainly by the paracellular route. Finally, the studyof the oral pharmacokinetics of nanoencapsulated IFN in BalbC mice revealed two maxima andarea-under-the-curve of 56.9 pg*h/mL.Fil: Imperiale, Julieta Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Schlachet, Inbar. Technion - Israel Institute of Technology; IsraelFil: Lewicki, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Sosnik, Alejandro Dario. Technion - Israel Institute of Technology; IsraelFil: Biglione, Mirna Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin
Chitosan-Grafted Copolymers and Chitosan-Ligand Conjugates as Matrices for Pulmonary Drug Delivery
Recently, much attention has been given to pulmonary drug delivery by means of nanosized systems to treat both local and systemic diseases. Among the differentmaterials used for the production of nanocarriers, chitosan enjoys high popularity due to its inherent characteristics such as biocompatibility, biodegradability, and mucoadhesion, among others. Through the modification of chitosan chemical structure, either by the addition of new chemical groups or by the functionalization with ligands, it is possible to obtain derivatives with advantageous and specific characteristics for pulmonary administration. In this paper, we discuss the advantages of using chitosan for nanotechnology-based pulmonary delivery of drugs and summarize the most recent and promising modifications performed to the chitosan molecule in order to improve its characteristics.Fil: Andrade, Fernanda. Universidad de Porto; PortugalFil: Goycoolea, Francisco. Westfalische Wilhelms Universitat; AlemaniaFil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Das Neves, José. Universidad de Porto; PortugalFil: Sosnik, Alejandro Dario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Sarmento, Bruno. Universidad de Porto; Portugal. Instituto Superior de Ciências da Saúde-Norte; Portuga
Biomateriais aplicados ao desenvolvimento de sistemas terapêuticos avançados
Esta obra apresenta contribuições que cobrem o estado-da-arte de vários tópicoscientíficos e técnicos e que foram desenvolvidos no âmbito das actividades científicase de formação de um projecto-em-rede CYTED, intitulado RIMADEL - Rede Ibero-Americana de Nuevos Materiales para el Diseño de Sistemas Avanzados de Liberación deFármacos en Enfermidades de Alto Impacto Socioeconómico.Este projecto pretendeu criar uma plataforma Ibero-Americana de intercâmbio deinvestigadores, de conhecimento e de recursos científicos e tecnológicos, orientadapara o desenvolvimento de novos biomateriais com aplicações em sistemas avançadosde libertação de agentes terapêuticos, e em suportes para dispositivos biomédicos eengenharia de tecidos/medicina regenerativa.Apresentam-se perspectivas abrangentes, embora muito actuais, e para que este livropossa servir também como uma obra de referência para estudantes de graduação e depós-graduação de países falantes da Língua Portuguesa ou Castelhana, em áreas comoa Engenharia (Engenharia Química, Engenharia de Materiais, Engenharia Biomédica,Engenharia Biológica), Ciências Farmacêuticas, Química, Química Medicinal, QuímicaBiológica, Bioquímica, e Biologia.</p
Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrin
The hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis in humans. Approximately 5% of the infected people die from cirrhosis or hepatocellular carcinoma. The current standard therapy comprises a combination of pegylated-interferon alpha and ribavirin. Due to the relatively low effectiveness, the prohibitive costs and the extensive side effects of the treatment, an intense research for new direct-acting anti-HCV agents is taking place. Furthermore, NS3 protease inhibitors recently introduced into the market are not effective against all HCV subgenotypes. Thiosemicarbazones (TSCs) have shown antiviral activity against a wide range of DNA and RNA viruses. However, their extremely low aqueous solubility and high self-aggregation tendency often preclude their reliable biological evaluation in vitro. In this work, we investigated and compared for the first time the anti-HCV activity of two 1-indanone TSCs, namely 5,6-dimethoxy-1-indanone TSC and 5,6-dimethoxy-1- indanone N4-allyl TSC, and their inclusion complexes with hydroxypropyl-β- cyclodextrin (HPβ-CD) in Huh-7.5 cells containing the full-length and the subgenomic subgenotype 1b HCV replicon system. Studies of physical stability in culture medium showed that free TSCs precipitated rapidly and formed submicron aggregates. Conversely, TSC complexation with HPβ-CD led to more stable systems with minimal size growth and drug concentration loss. More importantly, both TSCs and their inclusion complexes displayed a potent suppression of the HCV replication in both cell lines with no cytotoxic effects. The mechanism likely involves the inhibition of non-structural proteins of the virus. In addition, findings suggested that the cyclodextrin released the drug to the culture medium over time. This platform could be exploited for the study of the drug toxicity and pharmacokinetics animal models.Fil: Glisoni, Romina Julieta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cuestas, María Luján. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mathet, Veronica Lidia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Área Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Oubiña, Jose Raul. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Área Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Moglioni, Albertina Gladys. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sosnik, Alejandro Dario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
- …