The description also includes HA's objective, its sources, and its manufacturing processes, alongside its chemical and biological properties. Comprehensive insights are presented into the current uses of HA-modified noble and non-noble M-NPs, along with other substituents, in the field of cancer therapy. Furthermore, we discuss the possible obstacles to optimizing HA-modified M-NPs in terms of their clinical applicability, followed by a final assessment and potential future avenues.
Photodynamic diagnostics (PDD) and photodynamic therapy (PDT), well-established medical technologies, are used for the diagnosis and treatment of malignant neoplasms. Cancer cell visualization or destruction is achieved through the combination of photosensitizers, light, and oxygen. This review illustrates the recent advancements in these modalities, achieved with nanotechnology, including quantum dots as innovative photosensitizers or energy donors, and the use of liposomes and micelles. Target Protein Ligan chemical This literature review also examines the synergistic use of PDT alongside radiotherapy, chemotherapy, immunotherapy, and surgery for various types of neoplasms. The article's scope encompasses the latest advancements in PDD and PDT enhancements, showing great potential for the field of oncology.
A shift towards new therapeutic strategies is imperative for cancer therapy. Recognizing the critical part tumor-associated macrophages (TAMs) play in cancer's advancement, the re-education of these macrophages within the tumor microenvironment (TME) could be a potentially effective strategy in cancer immunotherapy. TAMs, via an irregular unfolded protein response (UPR) in their endoplasmic reticulum (ER), are primed to endure environmental stress and enhance anti-cancer immunity. Subsequently, nanotechnology could prove to be a desirable means of modifying the UPR in tumor-associated macrophages, enabling a distinct alternative to therapies focusing on macrophage repolarization. Genetic basis We developed and tested polydopamine-coated magnetite nanoparticles conjugated with small interfering RNAs (siRNAs) to reduce the expression of protein kinase R-like ER kinase (PERK) in TAM-like macrophages derived from murine peritoneal exudates (PEMs). After determining the cytocompatibility, cellular uptake, and gene silencing efficiency of the PDA-MNPs/siPERK in PEMs, we further analyzed their capacity to re-polarize macrophages in vitro from the M2 to the M1 anti-tumor inflammatory phenotype. PDA-MNPs, featuring both magnetic and immunomodulatory attributes, show cytocompatibility and the ability to redirect TAMs towards the M1 phenotype by inhibiting PERK, an effector molecule of the unfolded protein response that contributes to TAM metabolic adaptation. The development of novel in vivo tumor immunotherapies finds a new path based on these findings.
Oral intake's inherent side effects can be thoughtfully addressed via the transdermal administration route. Topical formulation design, seeking maximal drug efficiency, demands careful optimization of drug permeation and stability factors. The present investigation scrutinizes the physical constancy of non-crystalline pharmaceutical agents within the formulated mixture. Ibuprofen, a substance commonly used in topical preparations, was then selected as a model drug for investigation. Besides that, the material's low Tg contributes to surprising recrystallization at room temperature, impeding cutaneous absorption. In this investigation, the physical stability of amorphous ibuprofen is evaluated within two formulations: (i) terpene-based deep eutectic solvents, and (ii) arginine-based co-amorphous blends. The ibuprofenL-menthol phase diagram was analyzed mainly via low-frequency Raman spectroscopy, which provided evidence of ibuprofen recrystallization, evident in a broad span of ibuprofen concentrations. Studies have demonstrated that amorphous ibuprofen achieves stability when dissolved in a thymolmenthol DES solution. Immune evolutionary algorithm The melting process for creating co-amorphous blends of arginine and ibuprofen is an alternative approach to stabilizing amorphous ibuprofen, although recrystallization was observed in cryo-milled counterparts. Raman spectroscopic investigations in the C=O and O-H stretching regions provide a discussion of the stabilization mechanism, including determination of Tg and analysis of H-bonding interactions. The investigation revealed that ibuprofen recrystallization was prevented by an inability to form dimers, primarily due to the favored formation of heteromolecular hydrogen bonding, irrespective of the glass transition temperatures of the various mixtures. To anticipate the stability of ibuprofen in other topical products, this result is pivotal.
Recent years have witnessed extensive study of oxyresveratrol (ORV), a novel antioxidant. Artocarpus lakoocha, a primary source of ORV, has been a component of Thai traditional medicine for many years. However, the mechanism by which ORV contributes to skin inflammation is not well understood. In view of this, we investigated the anti-inflammatory effects of ORV in a dermatological model. Human immortalized and primary skin cells, exposed to bacterial components like peptidoglycan (PGN) and lipopolysaccharide (LPS), along with a 24-Dinitrochlorobenzene (DNCB)-induced dermatitis mouse model, underwent an examination of ORV's effect. Immortalized keratinocytes (HaCaT) and human epidermal keratinocytes (HEKa) experienced inflammation induced by PGN and LPS. In these in vitro models, the following assays were performed in sequence: MTT assays, Annexin V and PI assays, cell cycle analysis, real-time PCR, ELISA, and Western blot. Evaluation of the effects of ORV in a BALB/c mouse model of skin inflammation was performed using H&E staining, immunohistochemical staining with CD3, CD4, and CD8 markers. ORV's effect on HaCaT and HEKa cells, in the form of pretreatment, involved inhibiting the NF-κB pathway, thus mitigating the production of pro-inflammatory cytokines. When mice with DNCB-induced dermatitis were treated with ORV, there was a decrease in lesion severity, a reduction in skin thickness, and a decrease in the numbers of CD3, CD4, and CD8 T cells in the sensitized skin. Ultimately, the data indicates that ORV treatment effectively diminishes inflammation in in vitro skin inflammation models and in vivo dermatitis, suggesting a potential therapeutic use of ORV in managing skin conditions, including eczema.
The use of chemical cross-linking is a standard method in the development of HA-based dermal fillers for enhancing their mechanical qualities and extending their duration of action inside the body; however, an elevated injection force is frequently observed in clinical procedures when administering fillers with greater elasticity. A long-lasting and conveniently injectable dermal filler, a thermosensitive material, is presented as a low-viscosity liquid converting to a gel upon injection. Employing water as the solvent and green chemistry principles, HA was linked to poly(N-isopropylacrylamide) (pNIPAM), a thermosensitive polymer, using a linker. Hydrogels composed of HA-L-pNIPAM exhibited a comparatively low viscosity at room temperature, quantified by G' values of 1051 for Candidate1 and 233 for Belotero Volume. A significant stiffening of the gel occurred, accompanied by the formation of a submicron structure, upon reaching body temperature. Hydrogel formulations' robust resistance to enzymatic and oxidative degradation allowed for significantly lower injection forces (49 N for Candidate 1, compared to over 100 N for Belotero Volume) with a 32G needle. Biocompatible formulations (exhibiting L929 mouse fibroblast viability exceeding 100% and approximately 85% for the HA-L-pNIPAM hydrogel aqueous extract and its degradation product, respectively) provided extended residence times at the injection site, lasting up to 72 hours. The development of sustained-release drug delivery systems for dermatologic and systemic disorders is a potential application of this property.
During the development of semisolid topical products, the changes that the formulation undergoes in practical use situations are significant to consider. During this procedure, a multitude of critical quality characteristics, including rheological properties, thermodynamic activity, particle size, globule size, and the rate and extent of drug release or permeation, can be subject to modification. To explore the relationship between lidocaine-induced evaporation, consequent rheological modifications, and the permeation of active pharmaceutical ingredients (APIs) in topical semisolid products, this investigation was undertaken under realistic use scenarios. The evaporation rate of the lidocaine cream formulation was quantified using a DSC/TGA technique, which involved measuring the sample's weight loss and heat flow. By utilizing the Carreau-Yasuda model, metamorphosis-driven shifts in rheological properties were assessed and projected. A study investigated the effect of solvent evaporation on drug permeability using in vitro permeation testing (IVPT) with both occluded and unobstructed cell models. Analysis revealed a progressive augmentation of the lidocaine cream's viscosity and elastic modulus during evaporation, a phenomenon directly linked to the aggregation of carbopol micelles and the crystallization of the API after application. Lidocaine permeability in formulation F1 (25% lidocaine) showed a 324% reduction in unoccluded cells, relative to those that were occluded. It was concluded that the observed 497% permeability reduction after four hours was due to increasing viscosity and crystallization of lidocaine, not depletion of API from the applied dose. This conclusion was supported by formulation F2 with a higher API content (5% lidocaine), displaying a similar reduction in permeability. According to our findings, this appears to be the initial investigation showcasing the simultaneous rheological shift of a topical semisolid formulation during solvent volatilization. This associated decrease in API permeability offers a crucial foundation for mathematical modelers to construct complex models incorporating the interplay between evaporation, viscosity, and drug permeation in simulations, one at a time.