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1.
Macromol Biosci ; : e2400084, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733249

RESUMO

The targeted delivery of drugs using wireless navigable magnetic robots allows the delivery of drug molecules to be controlled non only in time but also in space, improving medical outcomes. The main disadvantages behind their use lies in the low amount of drug that can be transported and the single nature of drug that can be loaded (hydrophilic or hydrophobic). These considerations limit their use in co-delivery systems, now recognized to be very promising for many different pathologies. A magnetic bijel-like structure is developed to load and release different types of molecules (hydrophilic and hydrophobic). In this work, the use of ε-caprolactone is explored, which can polymerize, forming hydrophobic domains (oil phase). After mixing with iron oxide nanoparticles (NPs), the water dispersion creates a magnetic biphasic porous structure without phase separation. The resulting device shows good performance both in magnetic actuation and as a drug delivery system.

3.
Gels ; 10(1)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38247794

RESUMO

Bijels are a peculiar type of Pickering emulsion that have a bicontinuous morphology and are stabilised by a jammed layer of nanoparticles (NPs). Due to their double nature, their usage has increased in recent years in various fields, such as biological and food applications. In fact, they can release both hydrophilic and hydrophobic compounds simultaneously. An improvement to this structure is the use of a hydrophobic monomer like polycaprolactone as the organic phase, which is able to polymerise during the formation of the structure. Unfortunately, the structures formed in this way always have some drawbacks, such as their thermal stability or degradation when submerged in an aqueous medium. A number of studies have been carried out in which some parameters, such as the NPs or the monomer, were changed and their effect on the final product evaluated. In this work, the effect of modifying the aqueous phase was studied. In particular, the effect of adding alginate, a biopolymer capable of forming a stable hydrogel in the presence of divalent cations, was analysed, as was the difference between soaking or not in CaCl2, the final system. Specific attention was paid to their swelling behaviour (150% vs. 25% of the blank sample), rheological properties (G' 100 kPa vs. 20 kPa of the blank sample) and their release performances. In this framework, complete release of hydrophilic drug vs. 20% in the blank sample was observed together with improved release of the hydrophobic one with 35% in 8 h vs. 5% in the case of the blank sample. This strategy has been proven to influence bijels' properties, opening the doors to many different uses.

4.
Adv Mater ; 36(3): e2307747, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37990971

RESUMO

Current treatments for modulating the glial-mediated inflammatory response after spinal cord injury (SCI) have limited ability to improve recovery. This is quite likely due to the lack of a selective therapeutic approach acting on microgliosis and astrocytosis, the glia components most involved after trauma, while maximizing efficacy and minimizing side effects. A new nanogel that can selectively release active compounds in microglial cells and astrocytes is developed and characterized. The degree of selectivity and subcellular distribution of the nanogel is evaluated by applying an innovative super-resolution microscopy technique, expansion microscopy. Two different administration schemes are then tested in a SCI mouse model: in an early phase, the nanogel loaded with Rolipram, an anti-inflammatory drug, achieves significant improvement in the animal's motor performance due to the increased recruitment of microglia and macrophages that are able to localize the lesion. Treatment in the late phase, however, gives opposite results, with worse motor recovery because of the widespread degeneration. These findings demonstrate that the nanovector can be selective and functional in the treatment of the glial component in different phases of SCI. They also open a new therapeutic scenario for tackling glia-mediated inflammation after neurodegenerative events in the central nervous system.


Assuntos
Polietilenoglicóis , Polietilenoimina , Traumatismos da Medula Espinal , Camundongos , Animais , Nanogéis/uso terapêutico , Traumatismos da Medula Espinal/patologia , Neuroglia/patologia , Microglia
5.
Int J Biol Macromol ; 252: 126284, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37572821

RESUMO

Agarose hydrogels are three-dimensional hydrophilic polymeric frameworks characterised by high water content, viscoelastic properties, and excellent ability as cell and drug delivery systems. However, their hydrophilicity as gel systems makes loading of hydrophobic drugs difficult and often ineffective. The incorporation of amphiphilic molecules (e.g. cyclodextrins) into hydrogels as hosts able to form inclusion complexes with hydrophobic drugs could be a possible solution. However, if not properly confined, the host compounds can get out of the network resulting in uncontrolled release. Therefore, in this work, ß-cyclodextrins-based host-guest supramolecular hydrogel systems were synthesised, with ß-cyclodextrins (ß-CD) covalently bound to the polymeric network, preventing leakage of the host molecules. Hydrogels were prepared at two different ß-CD-functionalized polyvinyl alcohol (PVA)/agarose ratios, and characterised chemically and physically. Then ibuprofen, a drug often used as a gold standard in studies involving ß-CD both in its hydrophilic and hydrophobic forms, was selected to investigate the release behavior of the synthesised hydrogels and the influence of ß-CD on the release. The presence of ß-CD linked to the polymeric 3D network ensured a higher and prolonged release profile for the hydrophobic drug and also seemed to have some influence on the hydrophilic one.


Assuntos
Ciclodextrinas , beta-Ciclodextrinas , Ibuprofeno , Sefarose , Hidrogéis/química , beta-Ciclodextrinas/química , Sistemas de Liberação de Medicamentos , Ciclodextrinas/química , Polímeros
6.
Carbohydr Polym ; 301(Pt A): 120309, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36436870

RESUMO

Hydrogels based on hyaluronic acid (HA) and agarose-carbomer (AC) raised an increasing interest as drug delivery systems. The complex architecture of the polymer network, such as mesh size, HA molecular weight and drug-polymer non covalent interactions across the 3D polymer matrix strongly influence the release capability/profile of these materials. In this study, AC-HA hydrogels with different mesh sizes have been prepared and characterised. High Resolution Magic Angle Spinning (HR-MAS) NMR spectroscopy has been used to investigate the motion of two drugs, such as ethosuximide (neutral molecule) and sodium salicylate (net negative charge) within the AC and AC-HA hydrogel networks. Analysis of the experimental data provides evidence of superdiffusive motion for all formulations containing sodium salicylate, while ethosuximide molecules undergo unrestricted diffusion within the gel matrix. We further speculate that the superdiffusive motion, observed at the nanoscale, can be responsible for the faster release of sodium salicylate from all hydrogel formulations.


Assuntos
Ácido Hialurônico , Hidrogéis , Hidrogéis/química , Ácido Hialurônico/química , Salicilato de Sódio , Etossuximida , Espectroscopia de Ressonância Magnética , Sefarose/química
7.
ACS Omega ; 7(47): 42845-42853, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36467913

RESUMO

Bijels (bicontinuous interfacially jammed emulsion gels) raised an increasing interest as biomaterials for controlled drug delivery due to their biphasic nature organized in mesoscopic tortuous domains. Two bijel formulations were prepared and explored as delivery systems for both hydrophilic and lipophilic drugs, ethosuximide and dimethyl fumarate. The two bijel-like structures, based on polymerized ε-caprolactone/water, differ in the stabilizing nanoparticle hydroxyapatite (inorganic) and nanogel-based nanoparticles (organic). Diffusion nuclear magnetic resonance spectroscopy has been used to characterize the bijel structure and the transport behavior of the drug molecules confined within the water/organic interconnected domains. A reduced diffusion coefficient is observed for several concentrations of the drugs and both bijel formulations. Moreover, in vitro release profiles also reveal the effect of the microstructure and drug-nanoparticle interactions.

8.
Biomedicines ; 10(7)2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35884981

RESUMO

Spinal cord injury (SCI) is an injurious process that begins with immediate physical damage to the spinal cord and associated tissues during an acute traumatic event. However, the tissue damage expands in both intensity and volume in the subsequent subacute phase. At this stage, numerous events exacerbate the pathological condition, and therein lies the main cause of post-traumatic neural degeneration, which then ends with the chronic phase. In recent years, therapeutic interventions addressing different neurodegenerative mechanisms have been proposed, but have met with limited success when translated into clinical settings. The underlying reasons for this are that the pathogenesis of SCI is a continued multifactorial disease, and the treatment of only one factor is not sufficient to curb neural degeneration and resulting paralysis. Recent advances have led to the development of biomaterials aiming to promote in situ combinatorial strategies using drugs/biomolecules to achieve a maximized multitarget approach. This review provides an overview of single and combinatorial regenerative-factor-based treatments as well as potential delivery options to treat SCIs.

9.
Drug Deliv Transl Res ; 12(8): 1928-1942, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35152363

RESUMO

Recently, hydrogels have gained significant importance in different applications, such as tissue engineering and drug delivery. They are 3D structures of hydrophilic polymers held together through physical or chemical crosslinking. Important is their ability to swell in presence of solvents, forming elastic gels able to maintain their original shape. Furthermore, these scaffolds slowly degrade in the physiological environment, leading the growing tissue to replace the former filled site. In this work, hydrogels have been synthetized using branched polyacrylic acid (carbomer) cross-linked with an aliphatic polyetherdiamine (elastamine). In particular, we focused on the description of their equilibrium conditions in swollen state and the dynamic simulation of the swelling process. These hydrogels exhibited a peculiar swelling behaviour characterized by an overshoot of the volume increase before reaching the equilibrium. Notably, such behaviour was found at different pH values. In this manuscript, the swelling behaviour was studied by mathematical modelling. Moreover, the ability of these devices to release drugs was also examined through a literature model to understand the different operating transport mechanisms.


Assuntos
Sistemas de Liberação de Medicamentos , Hidrogéis , Hidrogéis/química , Modelos Teóricos , Polímeros/química , Engenharia Tecidual
10.
Front Bioeng Biotechnol ; 9: 692648, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722474

RESUMO

Targeted drug delivery from untethered microrobots is a topic of major interest in current biomedical research. The possibility to load smart materials able to administer active principles on remotely in vivo guidable microdevices constitutes one of the most attractive opportunities to overcome the drawbacks of classical untargeted delivery methodologies. Hydrogels, in particular, are ideal candidates as drug-carrying materials due to their biocompatibility, low cost, and ease of manufacturing. On the other hand, these polymers suffer from poor control over release rate and overall released amount. Starting from these premises, the present article demonstrates the possibility to tune the release of hydrogels applied on magnetically steerable microrobots by fabricating microsystems via layer-by-layer self-assembly. By doing this, the diffusion of chemicals from the hydrogel layers to the external environment can be optimized and the phenomenon of burst release can be strongly limited. The microrobotic platforms employed to transport the hydrogel active material are fabricated by employing 3D printing in combination with wet metallization and present a gold layer on their surface to enhance biocompatibility. The maneuverability of microdevices coated with both thin and thick multilayers is investigated, individuating optimized parameters for efficient actuation.

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