The aim of this study is to introduce a dental capping agent for the treatment of pulp inflammation (pulpitis). Nanohydroxyapatite with Elaeagnus angustifolia L. extract (nHAEA) loaded with metronidazole (nHAEA@MTZ) was synthesized and evaluated using a lipopolysaccharide (LPS) in vitro model of pulpitis. nHAEA was synthesized through sol-gel method and analyzed using Scanning Electron Microscopy, Transmission Electron Microscopy, and Brunauer Emmett Teller. Inflammation in human dental pulp stem cells (HDPSCs) induced by LPS. A scratch test assessed cell migration, RT PCR measured cytokines levels, and Alizarin red staining quantified odontogenesis. The nHAEA nanorods were 17-23 nm wide and 93-146 nm length, with an average pore diameter of 27/312 nm, and a surface area of 210.89 m2/g. MTZ loading content with controlled release, suggesting suitability for therapeutic applications. nHAEA@MTZ did not affect the odontogenic abilities of HDPSCs more than nHAEA. However, it was observed that nHAEA@MTZ demonstrated a more pronounced anti-inflammatory effect. HDPSCs treated with nanoparticles exhibited improved migration compared to other groups. These findings demonstrated that nHAEA@MTZ could be an effective material for pulp capping and may be more effective than nHAEA in reducing inflammation and activating HDPSCs to enhance pulp repair after pulp damage.

Inflammation-related diseases impose a significant global health burden, necessitating urgent exploration of novel treatment modalities for improved clinical outcomes. We begin by discussing the limitations of conventional approaches and underscore the pivotal involvement of immune cells in the inflammatory process. Amidst the rapid growth of immunology, the therapeutic potential of immune cell-derived extracellular vesicles (EVs) has garnered substantial attention due to their capacity to modulate inflammatory response. We provide an in-depth examination of immune cell-derived EVs, delineating their promising roles across diverse disease conditions in both preclinical and clinical settings. Additionally, to direct the development of the next-generation drug delivery systems, we comprehensively investigate the engineered EVs on their advanced isolation methods, cargo loading techniques, and innovative engineering strategies. This review ends with a focus on the prevailing challenges and considerations regarding the clinical translation of EVs in future, emphasizing the need of standardized characterization and scalable production processes. Ultimately, immune cell-derived EVs represent a cutting-edge therapeutic approach and delivery platform, holding immense promise in precision medicine.

Medulloblastoma (MB) is a major pediatric malignant brain tumor that arises in the cerebellum. MB tumors exhibit highly heterogeneous driven by diverse genetic alterations and could be divided into four major subgroups based on their different biological drivers and molecular features (Wnt, Sonic hedgehog (Shh), group 3, and group 4 MB). Even though the therapeutic strategies for each MB subtype integrate their pathogenesis and were developed to focus on their specific target sites, the unexpected drug non-selective cytotoxicity, low drug accumulation in the brain, and complexed MB tumor microenvironment still be huge obstacles to achieving satisfied MB therapeutic efficiency. This review discussed the current advances in modern MB therapeutic strategy development. Through the recent advances in knowledge of the origin, molecular pathogenesis of MB subtypes and their current therapeutic barriers, we particularly reviewed the current development in advanced MB therapeutic strategy committed to overcome MB treatment obstacles, focusing on novel signaling pathway targeted therapeutic agents and their combination discovery, advanced drug delivery systems design, and MB immunotherapy strategy development.

Alginates (ALG) have been used in biomedical and pharmaceutical technologies for decades. ALG are natural polymers occurring in brown algae and feature multiple advantages, including biocompatibility, low toxicity and mucoadhesiveness. Moreover, ALG demonstrate biological activities per se, including anti-hyperlipidemic, antimicrobial, anti-reflux, immunomodulatory or anti-inflammatory activities. ALG are characterized by gelling ability, one of the most frequently utilized properties in the drug form design. ALG have numerous applications in pharmaceutical technology that include micro- and nanoparticles, tablets, mucoadhesive dosage forms, wound dressings and films. However, there are some shortcomings, which impede the development of modified-release dosage forms or formulations with adequate mechanical strength based on pure ALG. Other natural polymers combined with ALG create great potential as drug carriers, improving limitations of ALG matrices. Therefore, in this paper, ALG blends with pectins, chitosan, gelatin, and carrageenans were critically reviewed.

OBJECTIVE: Periodontal disease (PD), defined as oral inflammation caused by dental plaque, is an emerging problem. PD may lead to tooth loss, and treatment options are limited. In this study, we designed, synthesized, and characterized silver nanoparticles (AgNPs) conjugated with chlorhexidine (AgNPs-CHL) or metronidazole (AgNPs-PEG-MET) to determine whether they can be used to treat PDs.
METHODS: AgNPs were synthesized and characterized by transmission electron microscopy, UV-vis spectrometry, thermogravimetric analyses, and dynamic light scattering. We determined the safety and the antimicrobial and anti-inflammatory properties of synthesized AgNPs in an in vitro model of periodontitis. Antimicrobial properties were determined by measuring the minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) on reference strains of bacteria and fungi. Human gingival fibroblast (HGF-1), murine macrophage (RAW264.7) and human foetal osteoblast (hFOB1.19) cells were used in the study. Lipopolysaccharide (LPS) was used to induce inflammation. Cytokine levels were measured using an enzyme-linked immunosorbent assay; metalloproteinase expression was measured using Western blotting.
RESULTS: The synthesized AgNPs were spherical and narrow-dispersed with an average diameter of 13.4 nm ± 3.0 nm in the case of AgNPs-CHL and 3.72 nm ± 0.72 nm in the case of AgNPs-PEG-MET. Both types of AgNPs were active against bacteria and fungi. AgNPs-CHL proved to be a more potent antimicrobial agent, although they were more cytotoxic than AgNPs-PEG-MET; however, both demonstrated beneficial properties in nontoxic concentrations. AgNPs-CHL and AgNPs-PEG-MET decreased the production of proinflammatory cytokines IL-1β, IL-6, IL-8 and TNFα. Both agents also decreased the levels of metalloproteinases MMP3 and MMP8, which may indicate that they will inhibit tissue degradation.
CONCLUSIONS: AgNPs-CHL and AgNPs-PEG-MET may be possible therapeutic options for PD, as they have antibacterial and anti-inflammatory properties. However, to fully understand the potential of AgNPs, our in vitro findings must be evaluated in an in vivo model.

The devastating nature of cancer continues to be one of the leading causes of death in the world. Chemotherapy is among the most common forms of cancer treatment but comes with a host of adverse effects caused by the therapeutic agents damaging healthy tissue and organs. To limit these side effects, scientists have been designing stimuli responsive drug delivery vessels for targeted release. This Review focuses on the incorporation of stimuli responsive linkages in targeted drug delivery systems to enhance therapeutic efficiency. These platforms are primarily employed to control the distribution of anticancer agents in the body to reduce the adverse side effects caused by their toxicities. We will outline how drug delivery vessels are constructed so that exposure to select environmental and external stimuli releases the enclosed drug only at the target site. Stimuli responsive components are integrated within drug delivery vessels in the form of cross-linkers, polymers, and surface modifications. The changes, these moieties undergo upon stimuli exposure, cascade into larger scale alterations to the platforms, resulting in complete disassembly, reversible morphological variations, and enhanced cellular uptake. The ability for these modes of delivery to be initiated exclusively under stimuli exposure allows for release of toxic therapeutic agents to be confined only to the affected area.

In the last decades, much research has been done to fasten wound healing and target-direct drug delivery. Hydrogel-based scaffolds have been a recurrent solution in both cases, with some reaching already the market, even though their mechanical stability remains a challenge. To overcome this limitation, reinforcement of hydrogels with fibers has been explored. The structural resemblance of fiber-hydrogel composites to natural tissues has been a driving force for the optimization and exploration of these systems in biomedicine. Indeed, the combination of hydrogel-forming techniques and fiber spinning approaches has been crucial in the development of scaffolding systems with improved mechanical strength and medicinal properties. In this review, a comprehensive overview of the recently developed fiber-hydrogel composite strategies for wound healing and drug delivery is provided. The methodologies employed in fiber and hydrogel formation are also highlighted, together with the most compatible polymer combinations, as well as drug incorporation approaches creating stimuli-sensitive and triggered drug release towards an enhanced host response.

Membrane active peptides (MAPs) represent a class of short biomolecules that have shown great promise in facilitating intracellular delivery without disrupting cellular plasma membranes. Yet their clinical application has been stalled by numerous factors: off-target delivery, a requirement for high local concentration near cells of interest, degradation en route to the target site, and in the case of cell-penetrating peptides, eventual entrapment in endolysosomal compartments. The current method of deriving MAPs from naturally occurring proteins has restricted the discovery of new peptides that may overcome these limitations. Here, we describe a new branch of assays featuring high-throughput functional screening capable of discovering new peptides with tailored cell uptake and endosomal escape capabilities. The one-bead-one-compound (OBOC) combinatorial method is used to screen libraries containing millions of potential MAPs for binding to synthetic liposomes, which can be adapted to mimic various aspects of limiting membranes. By incorporating unnatural and d-amino acids in the library, in addition to varying buffer conditions and liposome compositions, we have identified several new highly potent MAPs that improve on current standards and introduce motifs that were previously unknown or considered unsuitable. Since small variations in pH and lipid composition can be controlled during screening, peptides discovered using this methodology could aid researchers building drug delivery platforms with unique requirements, such as targeted intracellular localization.