RESUMO
Designing effective drug nanocarriers that are easy to synthesize, robust, and nontoxic is a significant challenge in nanomedicine. Polyamine-multivalent molecule nanocomplexes are promising drug carriers due to their simple and all-aqueous manufacturing process. However, these systems can present issues of colloidal instability over time and cellular toxicity due to the cationic polymer. In this study, we finely modulate the formation parameters of poly(allylamine-tripolyphosphate) complexes to jointly optimize the robustness and safety. Polyallylamine was ionically assembled with tripolyphosphate anions to form liquid-like nanocomplexes with a size of around 200 nm and a zeta potential of -30 mV. We found that nanocomplexes exhibit tremendous long-term stability (9 months of storage) in colloidal dispersion and that they are suitable as protein-loading agents. Moreover, the formation of nanocomplexes induced by tripolyphosphate anions produces a switch-off in the toxicity of the system by altering the overall charge from positive to negative. In addition, we demonstrate that nanocomplexes can be internalized by bone-marrow-derived macrophage cells. Altogether, these nanocomplexes have attractive and promising properties as delivery nanoplatforms for potential therapies based on the immune system activation.
Assuntos
Alilamina , Polifosfatos , Portadores de Fármacos , PolímerosRESUMO
Multistage delivery systems with size reduction capacity have been proposed as a powerful strategy for improving tissue drug penetration. Here we developed a simple and fast supramolecular approach to construct size-shrinkable polyamine-salt aggregates by ionic cross-linking of biodegradable poly-L-lysine dendrigraft with tripolyphosphate anion. The use of a peptide dendrimer as a nanobuilding block (â¼7 nm in diameter) allows the formation of supraparticles (SPs) with well-defined dimensions (â¼200 nm in diameter), narrow size distribution and great capacity to encapsulate different molecules, including chemotherapeutic agents as Curcumin and Doxorubicin. When exposed to slightly acidic environments, the crosslinked matrix is instantaneously disassembled to free dendrimer units. Subsequently, model cargo molecules entrapped in the dendrimer architecture can be released by the action of trypsin enzyme through peptide biodegradation. Therefore, these SPs with proved sequential pH and enzyme-responsiveness could be exploited as nanocarriers in multistage drug delivery systems.
Assuntos
Curcumina/química , Dendrímeros/química , Doxorrubicina/química , Peptídeos/química , Tripsina/química , Curcumina/metabolismo , Dendrímeros/síntese química , Dendrímeros/metabolismo , Doxorrubicina/metabolismo , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Substâncias Macromoleculares/química , Substâncias Macromoleculares/metabolismo , Estrutura Molecular , Tamanho da Partícula , Peptídeos/síntese química , Peptídeos/metabolismo , Poliaminas/química , Poliaminas/metabolismo , Polilisina/química , Polilisina/metabolismo , Propriedades de Superfície , Tripsina/metabolismoRESUMO
Polyamine-salt aggregates (PSA) are biomimetic soft materials that have attracted great attention due to their straightforward fabrication methods, high drug-loading efficiencies, and attractive properties for pH-triggered release. Herein, a simple and fast multicomponent self-assembly process was used to construct cross-linked poly(allylamine hydrochloride)/phosphate PSAs (hydrodynamic diameter of 360â nm) containing glucose oxidase enzyme, as a glucose-responsive element, and human recombinant insulin, as a therapeutic agent for the treatment of diabetes mellitus (GI-PSA). The addition of increasing glucose concentrations promotes the release of insulin due to the disassembly of the GI-PSAs triggered by the catalytic in situ formation of gluconic acid. Under normoglycemia, the GI-PSA integrity remained intact for at least 24â h, whereas hyperglycemic conditions resulted in 100 % cargo release after 4â h of glucose addition. This entirely supramolecular strategy presents great potential for the construction of smart glucose-responsive delivery nanocarriers.
Assuntos
Sistemas de Liberação de Medicamentos , Glucose/química , Insulina/administração & dosagem , Insulina/química , Nanocápsulas/química , Poliaminas/química , Reagentes de Ligações Cruzadas/química , Diabetes Mellitus/tratamento farmacológico , Gluconatos/química , Humanos , Insulina/farmacologiaRESUMO
Responsive nanomaterials have emerged as key components in materials sciences. Herein, we report the one-step preparation of multi-stimuli responsive polyamine-salt aggregates (PSA) by ionically crosslinking polyethylenimine with potassium ferrioxalate (FeOx). The unique properties of FeOx enables a novel class of soft nanomaterial that disassembles by exposure to light, reducing environments and temperature.