Hybrid Hydrogels for Synergistic Periodontal Antibacterial Treatment with Sustained Drug Release and NIR-Responsive Photothermal Effect.

BACKGROUND: Periodontal pathogenic bacteria promote the destruction of periodontal tissues and cause loosening and loss of teeth in adults. However, complete removal of periodontal pathogenic bacteria, at both the bottom of the periodontal pocket and the root bifurcation area, remains challenging. In this work, we explored a synergistic antibiotic and photothermal treatment, which is considered an alternative strategy for highly efficient periodontal antibacterial therapy. METHODS: Mesoporous silica (MSNs) on the surface of Au nanobipyramids (Au NBPs) were designed to achieve the sustained release of the drug and photothermal antibacterials. The mesoporous silica-coated Au NBPs (Au NBPs@SiO2) were mixed with gelatin methacrylate (GelMA-Au NBPs@SiO2). Au NBPs@SiO2 and GelMA-Au NBPs@SiO2 hybrid hydrogels were characterized, and the drug content and photothermal properties in terms of the release profile, bacterial inhibition, and cell growth were investigated. RESULTS: The GelMA-Au NBPs@SiO2 hybrid hydrogels showed controllable minocycline delivery, and the drug release rates increased under 808 nm near-infrared (NIR) light irradiation. The hydrogels also exhibited excellent antibacterial properties, and the antibacterial efficacy of the antibiotic and photothermal treatment was as high as 90% and 66.7% against Porphyromonas gingivalis (P. gingivalis), respectively. Moreover, regardless of NIR irradiation, cell viability was over 80% and the concentration of Au NBPs@SiO2 in the hybrid hydrogels was as high as 100 µg/mL. CONCLUSION: We designed a new near-infrared light (NIR)-activated hybrid hydrogel that offers both sustained release of antibacterial drugs and photothermal treatment. Such sustained release pattern yields the potential to rapidly eliminate periodontal pathogens in the periodontal pocket, and the photothermal treatment maintains low bacterial retention after the drug treatment.

Injectable in Situ Forming Hydrogels of Thermosensitive Polypyrrole Nanoplatforms for Precisely Synergistic Photothermo-Chemotherapy.

The combination of photothermal therapy (PTT) with chemotherapy has great potential to maximize the synergistic effect of thermo-induced chemosensitization and improve treatment performance. To achieve high drug-loading capacity as well as precise synchronization between the controllable release of chemotherapeutics and the duration of near-infrared PTT, in this work, a facile one-step method was first developed to fabricate a novel injectable in situ forming photothermal modulated hydrogel drug delivery platform (D-PPy@PNAs), in which a PNIPAM-based temperature-sensitive acidic triblock polymer [poly(acrylic acid-b-N-isopropylamide-b-acrylic acid (PNA)] was utilized as the stabilizing agent in the polymerization of polypyrrole (PPy). The in situ forming hydrogels showed a sensitive temperature-responsive sol-gel phase-transition behavior, as well as an excellent photothermal property. The strong interaction of ionic bonds together with π-π stacking interactions resulted in high doxorubicin (DOX) loading capacity and controlled/sustained drug release behavior. In addition, D-PPy@PNAs also displayed enhanced cellular uptake and promoted intratumoral penetration of DOX upon NIR laser irradiation. The synergistic photothermal therapy-chemotherapy of D-PPy@PNA hydrogels greatly improved the antitumor efficacy in vivo. Therefore, thermosensitive polypyrrole-based D-PPy@PNA hydrogels may be powerful drug delivery nanoplatforms for precisely synergistic photothermo-chemotherapy of tumors.

γ-Irradiated chitosan based injectable hydrogels for controlled release of drug (Montelukast sodium).

Novel pH-sensitive γ-irradiated low molecular weight (MW) chitosan (CS) (pre-irradiated) and poly (vinyl alcohol) (PVA) blended injectable hydrogels, crosslinked with varying concentrations of glycerol, were fabricated for drug delivery application. The effect of low MW irradiated CS on controlled drug release was evaluated to address the problem of higher viscosity and lower solubility of high MW CS. The FTIR spectra of hydrogels depicted the presence of all the incorporated functional groups and the developed interactions (physical and chemical). The surface morphology of hydrogels assessed by scanning electron microscope exhibited porous microstructure. All hydrogels were subjected to the swelling analysis in different media (water, buffer and electrolytes). The pH sensitive hydrogel samples exhibited less swelling at acidic and neutral pH while higher swelling at basic pH. CPG-0.5 showed the highest swelling at all pH media as compared to other hydrogel samples. CPG-1.0 was selected for the release analysis of drug because of its highest swelling (114.47%) in distilled water having neutral pH. It was loaded with model drug (Montelukast Sodium) during the preparation phase and studied for drug release capability. The in-vitro controlled release evaluation of hydrogel (CPG-1.0) was performed in SGF and SIF using UV-visible spectroscopy. The results confirmed their applications in injectable drug release systems as all the loaded drug was released in 30 min in SGF (pH -1.2) while the release of drug in SIF (pH -6.8) was in controlled manner (99.62% in 3 h). The improved antibacterial activity of these hydrogel films was owing to the fact that the γ-irradiated low MW CS has ruptured the bacterial cell and its metabolism more efficiently by inflowing in the cell.

Novel concept of the smart NIR-light-controlled drug release of black phosphorus nanostructure for cancer therapy.

A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release rates can be accurately controlled by light intensity, exposure duration, BP concentration, and hydrogel composition. Owing to sufficiently deep penetration of near-infrared (NIR) light through tissues, our BP-based system shows high therapeutic efficacy for treatment of s.c. cancers. Importantly, our drug delivery system is completely harmless and degradable in vivo. Together, our work proposes a unique concept for precision cancer therapy by external light excitation to release cancer drugs. If these findings are successfully translated into the clinic, millions of patients with cancer will benefit from our work.

Light-responsive iron(III)-polysaccharide coordination hydrogels for controlled delivery.

Visible-light responsive gels were prepared from two plant-origin polyuronic acids (PUAs), alginate and pectate, coordinated to Fe(III) ions. Comparative quantitative studies of the photochemistry of these systems revealed unexpected differences in the photoreactivity of the materials, depending on the polysaccharide and its composition. The roles that different functional groups play on the photochemistry of these biomolecules were also examined. Mannuronic-rich alginates were more photoreactive than guluronic acid-rich alginate and than pectate. The microstructure of alginates with different mannuronate-to-guluronate ratios changed with polysaccharide composition. This influenced the gel morphology and the photoreactivity. Coordination hydrogel beads were prepared from both Fe-alginate and Fe-pectate. The beads were stable carriers of molecules as diverse as the dye Congo Red, the vitamin folic acid, and the antibiotic chloramphenicol. The photoreactivity of the hydrogel beads mirrored the photoreactivity of the polysaccharides in solution, where beads prepared with alginate released their cargo faster than beads prepared with pectate. These results indicate important structure-function relationships in these systems and create guidelines for the design of biocompatible polysaccharide-based materials where photoreactivity and controlled release can be tuned on the basis of the type of polysaccharide used and the metal coordination environment.