RESUMEN
Conventional chemotherapeutic approaches currently used for brain tumor treatment have low efficiency in targeted drug delivery and often have non-target toxicity. Development of stable and effective drug delivery vehicles for the most incurable diseases is one of the urgent biomedical challenges. We have developed polymer nanoparticles (NPs) with improved temozolomide (TMZ) delivery for promising brain tumor therapy, performing a rational design of polyelectrolyte complexes of oppositely charged polysaccharides of cationic chitosan and anionic pectin. The NPs' diameter (30 to 330 nm) and zeta-potential (-29 to 73 mV) varied according to the initial mass ratios of the biopolymers. The evaluation of nanomechanical parameters of native NPs demonstrated changes in Young's modulus from 58 to 234 kPa and adhesion from -0.3 to -3.57 pN. Possible mechanisms of NPs' formation preliminary based on ionic interactions between ionogenic functional groups were proposed by IR spectroscopy and dynamic rheology. The study of the parameters and kinetics of TMZ sorption made it possible to identify compounds that most effectively immobilize and release the active substance in model liquids that simulate the internal environment of the body. A polyelectrolyte carrier based on an equal ratio of pectin-chitosan (0.1% by weight) was selected as the most effective for the delivery of TMZ among a series of obtained NPs, which indicates a promising approach to the treatment of brain tumors.
RESUMEN
Prospective adjuvant anticancer therapy development includes the establishing of drug delivery systems based on biocompatible and biodegradable carriers. We have designed films and nanoparticles (NPs) based on low-esterified pectin hydrogel using the ionic gelation method. We investigated morphology, nanomechanical properties, biocompatibility and anticancer activity. Hydrogel films are characterized by tunable viscoelastic properties and surface nanoarchitectonics through pectin concentration and esterification degree (DE), expressed in variable pore frequency and diameter. An in vitro study showed a significant reduction in metabolic activity and the proliferation of the U87MG human glioblastoma cell line, probably affected via the adhesion mechanism. Glioma cells formed neurosphere-like conglomerates with a small number of neurites when cultured on fully de-esterified pectin films and they did not produce neurites on the films prepared on 50% esterified pectin. Pectin NPs were examined in terms of size distribution and nanomechanical properties. The NPs' shapes were proved spherical with a mean diameter varying in the range of 90-115 nm, and a negative zeta potential from -8.30 to -7.86 mV, which indicated their stability. The NPs did not demonstrate toxic effect on cells or metabolism inhibition, indicating good biocompatibility. Nanostructured biomaterials prepared on low-esterified pectins could be of interest for biomedical applications in adjuvant anticancer therapy and for designing drug delivery systems.
RESUMEN
Brain tumors are the most difficult to treat, not only because of the variety of their forms and the small number of effective chemotherapeutic agents capable of suppressing tumor cells, but also limited by poor drug transport across the blood-brain barrier (BBB). Nanoparticles are promising drug delivery solutions promoted by the expansion of nanotechnology, emerging in the creation and practical use of materials in the range from 1 to 500 nm. Carbohydrate-based nanoparticles is a unique platform for active molecular transport and targeted drug delivery, providing biocompatibility, biodegradability, and a reduction in toxic side effects. However, the design and fabrication of biopolymer colloidal nanomaterials have been and remain highly challenging to date. Our review is devoted to the description of carbohydrate nanoparticle synthesis and modification, with a brief overview of the biological and promising clinical outcomes. We also expect this manuscript to highlight the great potential of carbohydrate nanocarriers for drug delivery and targeted treatment of gliomas of various grades and glioblastomas, as the most aggressive of brain tumors.