An injectable hydrogel based on oxidized agarose (OA) and carboxymethyl chitosan (CMCh) was developed with OA/CMCh variable proportions (60:40, 50:50, and 40:60) and evaluated. Its characterization was carried out through time gelation, injectability, syringeability, compression mechanical properties, swelling, and degradation. For all proportions, it was found that the hydrogel gelled before reaching 37 °C, and it proved to be suitable for injection through a 21 G gauge needle. Also, a direct relationship was identified between the CMCh amount added to the mixture and the evaluated properties of the hydrogel. The injectability (maximum injection force) for the 60:40 ratio was 12.84 N and increased by 62 % for the 40:60 ratio. Nevertheless, these were less than 30 N, which is the maximum force accepted for manual injection. Likewise, the 60:40 proportion presented a compressive strength of 26.92 kPa and increased by 72 % in the 40:60 proportion. Likewise, the swelling capacity increased from 1972 % to 3102 % for the same proportions, respectively. Furthermore, the increase in CMCh percentage was also associated with a decrease in the degradation rate; for example, the 40:60 ratio (14.28 %) was 32 % lower than the 60:40 ratio. In conclusion, for mixtures with higher CMCh content, the hydrogel's injectability, compressive strength, and swelling capacity increased. These results suggest that changing the proportion of OA:CMCh can modulate the material's properties, indicating its versatility and adaptability. It is a promising option for biomedical applications such as the local administration of active ingredients.

Purpose: Choroidal neovascularization (CNV) is a major cause of vision loss and blindness in wet macular degeneration. To treat CNV, intravitreal anti-vascular endothelial growth factor therapy (VEGF) such as bevacizumab (BEV) are often utilized, but these treatments require frequent invasive administration and can carry a risk of eye infection. To improve the treatment efficiency, reduce the treatment burden, and reduce side-effects and invasiveness, the current study describes a novel treatment of CNV using miniature biodegradable silicon nanoneedles (SiNNs) fabricated on a tear-soluble contact lens.

Methods: The SiNNs were encapsulated with BEV (BEV@SiNNs) and used as drug carriers for long-term, sustained drug delivery. BEV@SiNNs were evaluated on a New Zealand rabbit CNV model (n = 7) after approval from the University of Michigan IACUC. To generate CNV, subretinal injection of Matrigel (20 μL) and VEGF (7.5 μL, 100 μg/mL) was performed using a 30G Hamilton needle. A contact lens was inserted subconjunctivally on the posterior sclera 3 days after CNV creation and monitored by color fundus photography, OCT, and fluorescein angiography (FA) before and at 1, 3, 7, 14, and 28 days and then monthly for up to 1 year post-treatment.

Results: BEV@SiNNs resulted in long-term, sustained reduction in mean FA CNV leakage intensity for at least 1 year. There was a rapid 45% reduction in CNV within 1 week. CNV continued to gradually reduce further to an 80% reduction in CNV by 4 months that was persistent to 12 months. Control CNV did not have a significant change in CNV over 1 year. Rabbits were comfortable on the grimace scale, and no complications occurred with treatment in any animals. OCT showed normal retinal morphology and layers.

Conclusions: SiNNs are an efficient drug delivery platform technology for long-term (at least 1 year), sustained treatment of CNV in this rabbit model.

Introduction: Local recurrence in oncology is a significant issue, often due to chemotherapy limitations like drug concentration fluctuations in the tumor localization and non-specific action, leading to unstable therapeutic effects and reduced effectiveness. This research aimed to develop a biodegradable local chemotherapy platform for multi-month, controlled drug release.

Methods: A polycaprolactone (PCL) substrate was prepared using the solvent casting method followed by aminolysis on one side for the subsequent deposition of a multilayer coating containing doxorubicin (DOX). The substrate was analyzed using FTIR spectroscopy, SEM, colorimetrics, and wetting angle measurements. To stabilize the release of DOX, an ionic complex between poly-γ-glutamic acid (PGA) and DOX was formed. A coating was applied to the platform by layer-by-layer assembly of polyelectrolytes. Various coating deposition methods, different polycations, and the presence of empty polyelectrolyte bilayers were tested. The platform was analyzed using SEM, AFM and DSC. The empty platform was also tested for cytotoxicity and cytocompatibility using ovarian cancer cells (SKOV-3) and primary human fibroblasts. The in vitro activity of the released DOX was assessed using SKOV-3 cells.

Results: The amount of amino groups on the substrate surface after aminolysis was 118.1 μg/ml. The ionic complex between DOX and PGA was obtained with 99% efficiency and contained 99 μg/mg DOX. The total load of DOX in the platforms was 570 ng/cm². The release of DOX from the resulting platforms lasted for more than 5 months and was characterized by minimal explosive kinetics and uniformity. According to the results of in vitro studies, the platform showed no cytotoxicity, was characterized by good cytocompatibility and did not interfere with the antitumor activity of DOX.

Conclusions: This work is promising for drug delivery systems and therapeutics, as it compensates for the explosive nature of antineoplastic agents release in similar studies and has the highest prolonged release.

Given the optoelectronic properties of gallium arsenide (GaAs), it is currently a promising candidate for the development of optimal platforms for optical biosensing devices. The biofunctionalization of this semiconductor can be achieved using biomaterials extensively explored in life sciences for diagnostics. In this study, we investigate the synergistic impact of a functional biomaterial shell and a diatomic confining potential on the electronic and optical properties of GaAs/AlGaAs/bioshell spherical quantum dots. Calculations were conducted within the framework of effective mass and parabolic band approximations, solving the Schrödinger equation for a confined electron using the finite element method (FEM). Our findings reveal that alterations in the sizes of the GaAs core, AlGaAs shell, biomaterial shell, and confinement potential parameters result in significant variations in the energies of electron quantum dots and the optical absorption spectrum. We conclude that the diatomic confinement potential parameters enable adjustment of both ground and excited state energies, thereby modulating the amplitudes and positions of peaks in the obtained optical properties. This nuanced control over the quantum dot properties holds promise for tailoring device performance in optical biosensing applications. By enhancing sensitivity and specificity in detecting biomolecules, such devices could revolutionize biomedical diagnostics, offering rapid and accurate detection of diseases or biomarkers.

1. Introduction

Nanoparticles have gained significant attention in various scientific domains, especially medicine. Their applications span a wide range of fields including diagnostics, drug delivery antimicrobials, and cancer therapy [1]. The green synthesis of nanoparticles is favored over traditional physical and chemical methods as it is cost-effective, simple, and eco-friendly [2]. Silver nanoparticles (AgNPs) have been safely utilized in medicine. Previous studies have shown that bovine serum albumin (BSA) can be used as a capping agent for AgNPs for optimum drug delivery. Triple-negative breast cancer is an aggressive breast cancer subtype associated with poor prognosis due to a lack of targeted therapy. In this study, BSA-coated AgNPs were synthesized to examine their anti-cancer effects on triple-negative breast cancer cells (MDA-MB-231).

2. Methods

Using the green approach, BSA solution was added to silver salts to produce the BSA-coated silver nanoparticles with different concentrations. The presence of silver nanoparticles was examined using UV-Vis absorption spectra and transmission electron microscopy (TEM). Triple-negative breast cancer cells were treated with BSA-AgNPs. Untreated MDA-MB-23 cells were used as controls. Cell proliferation and morphology were assessed using light microscopy.

3. Preliminary Results

UV-Vis absorption spectra and TEM confirm the presence of AgNP nanoparticles in the size range of 15-16.50 nm. Through assessing the effect on breast cancer cells, silver nanoparticles exhibit dose-dependent toxicity against the MDA-MB-231 breast cancer cell line, which was evidenced by the typical signs of apoptosis including cell shrinkage and membrane blebbing 24 hours post-treatment

4. Conclusions and Future perspective

BSA-coated silver nanoparticles were successfully synthesized. The early findings indicate that the efficacy of protein-decorated silver nanoparticles against breast cancer cells is directly proportional to the dosage, primarily through the induction of apoptosis. BSA-coated silver nanoparticles have great potential in future cancer therapies. Nevertheless, future studies need to be conducted to examine their drug selectivity and in vivo effects.

The fabrication of composites based on different fillers has gained numerous considerations in the past decades in different areas of biomedical research. It is necessary for the chosen polymeric material as a continuous phase to have good compatibility with the fillers to form a unique biomedical system. Interfacial interactions between components of the system are also important for establishing characteristics of the resulting biomedical material. In this work, one polymer based on modified polysulfone (PSF) was considered a host matrix where modified carbon nanotubes with hydroxyl groups were added for the scope of fabricating a biocompatible material. A chlorometilation reaction was used to create aldehyde groups linked to PSF, which was further cross-linked by an oxidation reaction and acetilization of poly(vinyl alcohol) (PVA) to obtain a new modified PSF with side PVA groups. For comparison only, the new material was analyzed with another system containing PVA as a matrix where different concentrations of modified carbon nanotubes were added. The content ratio of modified carbon nanotubes varied between 0.5 to 5 wt%. Each prepared composite system was investigated by contact angle measurements. The compatibility with blood was determined by theoretical calculation and experimental analysis such as hemocompatibility. Materials were proved to be biocompatible, which leads to their recommendation as blood-contacting materials.

Magnetic resonance imaging (MRI) contrast can be enhanced through the use of magnetic nanoparticles. These nanoparticles alter the relaxation time of ¹H nuclei in water molecules that are present in tissues, providing sharper and more detailed images. The use of natural polymers such as sodium alginate, in addition to these being biocompatible and non-toxic, will ensure greater colloidal stability of the suspension, allowing for its use as a contrast agent for MRI. Therefore, this study aimed to prepare and analyze the behavior of iron oxide nanoparticles (FeNPs) to assess their potential application as a contrast agent for MRI diagnosis. FeNPs were prepared in an aqueous medium using the co-precipitation method. Subsequently, the surface of the nanoparticles was coated with different concentrations of sodium alginate (2.5, 5.0, 7.5, and 10.0 mg.mL^-1) to make FeNPs stable in an aqueous environment, as well as biocompatible. The efficiency of FeNPs (with and without alginate) as contrast agents was evaluated through relaxivity measurements (20 MHz at 25 ºC). The obtained results showed that with the addition of alginate, FeNPs showed a decrease in transverse relaxation time (T₂) compared to NPs without the polymer. These results may indicate that the incorporation of the stabilizer led to a change in the mobility of water molecules, thereby altering the diffusion time of water molecules near the superparamagnetic center and increasing the colloidal stability of iron oxide nanoparticles in a suspension. Thus, based on the obtained results, FeNP alginates show potential for use as biocompatible contrast agents for diagnostic imaging.

Introduction

Burns represent one of the most serious and painful skin injuries, with a significant impact on patients' quality of life and vital functions. The management of burns requires timely treatment and the use of innovative materials that promote effective wound healing. In this context, hydrogels are emerging as a promising therapeutic option due to their high hydrophilicity, good biocompatibility, and ability to provide an optimal environment for the regeneration of damaged skin tissue.

In this work, a new protocol was developed to fabricate a pH-responsive multilayer hydrogel patch based on biocompatible alginate (ALG) and containing different bioactive principles, such as manuka honey (MH), for its antibacterial properties.

Methods

The multiple layers of the patch were assembled by ionic crosslinking with a calcium chloride solution. The swelling ratio, water content, and porosity were evaluated to assess the hydrophilicity of the hydrogels and their ability to absorb exudate from the wound to promote healing and prevent infection. FTIR analysis was used to investigate the chemical composition of the patch layers, and DSC analysis was employed to evaluate the thermal stability in the physiological range. Water vapor transmission rates (WVTRs) were calculated to quantify the water vapor transmission through the patches. The degradation at different pH values was studied to establish the pH-responsive nature.

Results and Conclusions

Multilayer hydrogels were successfully prepared using ionic gelation. The samples showed a high water content (> 85%) and high porosity. They also showed good water vapor permeability, which demonstrates their potential use for the treatment of burns. The DSC analysis showed thermal stability in the physiological range. In conclusion, this work presents a promising innovation in the field of burn care, offering a new approach for improving burn management and healing.

Magnetic resonance imaging (MRI) is a non-invasive technique that offers advantages compared to others diagnostic methods. Due their low sensitivity, contrast agents (CAs) are employed to improve image contrast by reducing the relaxation times of water molecules within the medium. The main commercial CAs are Gd-based complexes, due to the presence of seven unpaired pairs of electrons in Gd³⁺ ion. Among them, those composed by the DOTA ligand are notable for their high thermodynamic and kinetic stability. Despite the efficiency of the Gd-DOTA complexes in enhancing contrast, nanoparticulate CAs have been used to further amplify the MRI signal. Gd-complexes have been attached to Quantum Dots (QDs), offering a secondary signal for optical imaging, combining the advantages of both techniques into a single system [1]. QDs are semiconductor nanocrystals characterized by a size range from 2 to 10 nm, possessing size-tunable optical properties and an active surface. These properties make them interesting for multiple fields of application, such as nanoprobes for diagnostic imaging. However, the majority of works published so far with this aim use Cd-based QDs or material that is synthesized via organic methods [2]. In order to utilize the material in biological applications, in this work, we synthesized Ag₂Se QDs in aqueous medium, and conjugated them to Gd-DOTA complexes through thiol–metal binding. The optical characterization showed an increase up to 43% of the emission intensity of the QDs after the conjugation procedures. Moreover, relaxometric studies showed an relaxivity values improvement of these nanosensors, compared with the clinical Gd-DOTA complex. These results demonstrated the potential of the systems based on Ag₂Se QDs and Gd-DOTA complex to serve as non-toxic optical probes in biomedical applications.

References:

[1] Albuquerque, G. M., et al. Topics in Current Chemistry, 2021, 379, 12, 1-35.

[2] Viegas, I. M. A., et al. New Journal of Chemistry, 2022, 46, 21864-21874.

There is growing interest in the development of nanomaterials that facilitate the high-precision detection of cancer cells with the least possible invasion of the body. The association of drugs and contrast agents for concomitant therapy and diagnostic is extremely important to follow the evolution of treatment. However, cancer drugs can often cause collateral damage to non-cancer cells and a promising alternative to these treatments is plasmonic photothermal therapy (PTT) [1]. The use of silver nanoparticles (AgNPs) present advantages over other metals, as it combines good qualities in terms of plasmonic feature, synthesis with high control over size and morphology, and cost-effectiveness. AgNPs also have the versatility to modify their surface, providing higher specificity and/or even a signal for a diagnostic technique, like magnetic resonance imaging (MRI). MRI is a non-invasive diagnostic tool that allows the differentiation between healthy and tumoral tissues. However, this technique commonly requires the use of contrast agents (ACs) to enhance the image contrast. Gd³⁺ chelates are the systems most used clinically as ACs and their conjugation with NPs allows a greater concentration of paramagnetic ions, generating a greater contrast without increasing their dosage. Bifunctional nanosystems based on AgNPs and Gd³⁺ chelates present the promising possibility to achieve theranostic nanoplatforms, combining the photothermal property of AgNPs with the relaxometric efficiency of Gd³⁺ chelates. Thus, AgNPs, with good chemical and colloidal stability and a prismatic shape, and DOTA-Gd complexes containing a thiol group were prepared. The obtained bifunctional nanosystems maintained the optical properties of AgNPs and showed longitudinal relativities for Gd³⁺ similar to the AC used clinically (at 20 MHz and 37 °C) [2]. Therefore, the results are promising for the preparation of theranostic systems for MRI and PTT.