Browsing by Author "Guerrero, Juan"

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    Colloidal nanomedicines with prolonged release of chloroquine based on interactions with aromatic polymers after mixing two liquids: from in silico simulation of nanoparticle formation to efficient in-bench scale up
    (2024) Villamizar-Sarmiento, Maria Gabriela; Yanez, Osvaldo; Flores, Mario E.; Alvarez-Acevedo, Gonzalo; Gonzalez-Nilo, Fernando; Guerrero, Juan; Moreno-Villoslada, Ignacio; Oyarzun-Ampuero, Felipe A.
    Nanomedicines containing the aromatic drug chloroquine and the polymer poly(sodium 4-styrenesulfonate) have been theoretically designed and experimentally synthesized following the simple mixture of two aqueous solutions containing the drug and the polymer, respectively. Theoretical calculations show higher binding energy between both the aromatic polymer and chloroquine, and a higher tendency to release water from their hydration spheres, as compared to the binding between the drug and the aliphatic polymer poly(sodium vinyl sulfonate). MD simulations show the spontaneous formation of stable structures of 10 nm of average diameter, even combining short polymer chains, highly diluted reactants, and short reaction time (in the range of mu s). Rapid mixture of the liquids in a stopped flow equipment shows nanoparticle formation in the range of tenths of seconds. Equilibration studies in the range of minutes evidence spheroidal nanoparticles with almost quantitative association efficiency, 48.6 % of drug loading, size of 170 - 410 nm, low polydispersity (PdI = 0.25 - 0.47), and negative zeta potential (-18 - -45 mV). They provide drug release for 30 days, and are stable to NaCl exposure, pH gradient, several temperature values, and long-term storage. Furthermore, we demonstrate scaling up of the nanomedicine production upon increasing the reaction volume. Our studies demonstrate that these highly loaded drug nanoparticles are based on the occurrence of site -specific short-range interactions between the drug and the aromatic excipient such as pi-stacking. In the absence of the aromatic group in the polymer, weak interactions and unstable formulations are evidenced, both theoretically and experimentally. The combination of the selected theoretical and experimental tools could promote the efficient production of drug / polyelectrolyte formulations with therapeutical applications. The chosen components could be considered as potential medicines or as model components to design, develop, characterize, and scale up medicines comprising other combinations of drugs and polymers.
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    Copper(I) complexes bases on a new indazol-4,7-dione ligand
    (2013) Escobar, Manuel A.; Jara, Danilo H.; Tapia Apati, Ricardo; Lemus, Luis; Fröehlich, Roland; Guerrero, Juan; Rojas Guerrero, René
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    Effects of non-covalent interactions on the electronic and electrochemical properties of Cu(i) biquinoline complexes
    (2018) Martínez Ahumada, Natalia del Pilar; Isaacs Casanova, Mauricio; Oliver, Allen G.; Ferraudi, G.; Graham Lappin, A.; Guerrero, Juan
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    The key role of the drug self-aggregation ability to obtain optimal nanocarriers based on aromatic-aromatic drug-polymer interactions
    (2021) Villamizar-Sarmiento, Maria Gabriela; Guerrero, Juan; Moreno-Villoslada, Ignacio; Oyarzun-Ampuero, Felipe A.
    The efficient association and controlled release of hydrophilic and aromatic low molecular-weight drugs (HALMD) still remains a challenge due to their relatively weak interactions with excipients and strong affinity to water. Considering that a wide variety of drugs to treat chronic diseases are HALMD, their inclusion in polymeric nanoparticles (NPs) constitutes an attractive possibility by providing to these drugs with controllable physiochemical properties, preventing crisis episodes, decreasing dose-dependent side effects and promoting therapeutic adhesiveness. However, the strong interaction of HALMD with the aqueous medium jeopardizes their encapsulation and controlled release. In this work, the role of the self-assembly tendency of HALMD on their association with the aromatic excipient poly(sodium 4-styrensulfonate) (PSS) to form NPs is studied. For this aim, the widely used drugs amitriptyline (AMT), promethazine (PMZ), and chlorpheniramine (CPM) are selected due to their well described critical aggregation concentration (cac) (36 mM for AMT, 36 mM for PMZ, and 69.5 mM for CPM). These drugs undergo aromatic-aromatic interactions with the polymer, which stabilize their mutual binding, as seen by NMR. The simple mixing of solutions of opposite charged molecules (drug + PSS) allowed obtaining NPs. Importantly, comparing the three drugs, the formation of NPs occurred at significantly lower absolute concentration and significantly lower drug/polymer ratio as the cac takes lower values, indicating a stronger binding to the polymer, as also deduced from the respective drug/polymer dissociation constant values. In addition, the number of formed NPs is similar for all formulations, even though a much lower concentration of the drug and polymer is present in systems comprising lower cac. The obtained NPs are spheroidal and present size between 100 and 160 nm, low polydispersity (<= 0.3) and negative zeta potential (from -30 to -60 mV). The association efficiency reaches values >= 83% and drug loading could achieve values up to 68% (never evidenced before for systems comprising HALMD). In addition, drug release studies are also significantly influenced by cac, providing more prolonged release for AMT and PMZ (lower cac), whose delivery profiles adjust to the Korsmeyer-Peppas equation. As a novelty of this work, a synergic contribution of drug selfassociation tendency and aromatic-aromatic interaction between the drug and polymers is highlighted, a fact that could be crucial for the rational design and development of efficient drug delivery systems.