Tyrosine kinase inhibitors, or TKIs, are a common treatment for chronic myeloid leukemia, or CML. Dasatinib, a tyrosine kinase inhibitor with a broad spectrum of action, has off-target effects that impart an immunomodulatory capability, resulting in heightened innate immune responses against cancerous and virally infected cells. Several research endeavors highlighted dasatinib's ability to expand memory-phenotype natural killer (NK) and T cells, elements demonstrably linked to enhanced CML control upon cessation of treatment. These innate cells, crucial in managing HIV infection, are associated with viral suppression and defense, hinting at dasatinib's potential to improve both CML and HIV outcomes. Additionally, dasatinib is capable of directly inducing apoptosis in senescent cells, potentially acting as a novel senolytic medication. This review delves into the current understanding of virological and immunogenetic factors contributing to the robust cytotoxic responses elicited by this medication. Furthermore, the discussion will include the potential therapeutic implications for chronic myeloid leukemia, HIV infection, and the effects of aging.
DTX, a non-selective antineoplastic drug with low solubility, is associated with a series of adverse side effects. Employing the principle of pH sensitivity, anti-epidermal growth factor receptor (anti-EGFR) immunoliposomes are designed to enhance the delivery of medication to tumor cells with elevated EGFR expression within an acidic tumor environment. The primary focus of the study was the development of pH-sensitive liposomes composed of DOPE (dioleoylphosphatidylethanolamine) and CHEMS (cholesteryl hemisuccinate), executed using a Box-Behnken factorial design. click here Our study further involved the conjugation of the monoclonal antibody cetuximab onto the liposomal surface, combined with a detailed characterization of the nanosystems and their evaluation in the context of prostate cancer cells. The characteristics of liposomes, resulting from the hydration of a lipid film and optimization by a Box-Behnken factorial design, included a particle size of 1072 ± 29 nm, a polydispersity index of 0.213 ± 0.005, a zeta potential of -219 ± 18 mV, and an encapsulation efficiency of 88.65 ± 2.03%. FTIR, DSC, and DRX analyses collectively confirmed the successful encapsulation of the drug, accompanied by a decrease in its crystallinity. Under acidic pH, drug release was substantial and elevated. Liposome-cetuximab (anti-EGFR antibody) conjugation proved successful in preserving the physicochemical characteristics of the liposomes. DTX-loaded liposomes achieved an IC50 of 6574 nM in PC3 cells and 2828 nM in DU145 cells. The IC50 value for immunoliposome treatment of PC3 cells was found to be 1521 nM, contrasting with the 1260 nM IC50 observed in DU145 cells, a significant boost in cytotoxicity against EGFR-positive cells. DU145 cells, characterized by elevated EGFR expression, experienced a quicker and more comprehensive internalization of immunoliposomes than the internalization of liposomes. Subsequently, utilizing these data, a formulation was achieved demonstrating the desired nanometric size, accompanied by a high encapsulation of DTX in liposomes, and, especially, in immunoliposomes with DTX incorporated. This, as was expected, resulted in diminished viability of prostate cells and substantial cellular internalization in EGFR-overexpressing cells.
With a slow onset but steady worsening, Alzheimer's disease (AD), a neurodegenerative ailment, progresses over time. Roughly seventy percent of global dementia cases are attributed to this condition, a matter of significant public health concern, as recognized by the WHO. Due to the multifactorial nature of Alzheimer's, a satisfactory understanding of its origins remains elusive. In spite of the vast medical expenditures and the relentless pursuit of new pharmaceuticals and nanomedicines in recent years, a cure for Alzheimer's Disease still evades discovery, and successful treatments are relatively scarce. This review explores the current specialized literature on brain photobiomodulation's molecular and cellular processes, exploring its added value as a complementary approach in the context of Alzheimer's Disease. Pharmaceutical formulations at the forefront of innovation, the creation of novel nanoscale materials, bio-nano-formulations in current applications, and insights into Alzheimer's disease are highlighted. This review also aimed to identify and accelerate the shift to entirely novel paradigms for managing multiple AD targets, fostering brain remodeling with innovative therapeutic models and cutting-edge light/laser-based medical applications within the integrative nanomedicine of the future. In closing, the integration of the newest photobiomodulation (PBM) clinical trial data with the most advanced nanoscale drug delivery techniques, designed to effortlessly overcome the protective barriers of the brain, could unlock new avenues for revitalizing our complex and fascinating central nervous system. Cross-barrier treatment for Alzheimer's disease may be facilitated by the innovative use of picosecond transcranial laser stimulation alongside the latest nanotechnologies, nanomedicines, and drug delivery systems. Intelligent and strategically focused multifunctional solutions and novel nanodrugs are poised to potentially revolutionize the treatment of Alzheimer's disease in the near future.
Current awareness of antimicrobial resistance is heightened by the misuse of antibiotics. The widespread application across various sectors has exerted substantial selective pressure on pathogenic and commensal bacteria, resulting in the emergence of antimicrobial resistance genes, severely impacting human health. A potentially successful strategy, amongst the multitude of options, could involve the creation of medical features employing essential oils (EOs), elaborate natural mixtures drawn from diverse plant organs, abundant in organic compounds, some of which manifest antiseptic properties. Cyclodextrins (CDs), cyclic oligosaccharides, were used to encapsulate the green extracted essential oil of Thymus vulgaris, resulting in tablet formation. This essential oil effectively combats both fungi and bacteria, demonstrating broad-spectrum efficacy. The inclusion of this component permits its effective deployment, lengthening exposure time to active compounds and thereby producing a more prominent efficacy against biofilm-forming microorganisms, notably P. aeruginosa and S. aureus. The tablet's effectiveness against candidiasis suggests its potential use as a chewable for oral candidiasis and a vaginal tablet for vaginal candidiasis. Subsequently, the broad spectrum of efficacy registered is even more favorable, as the proposed method is undeniably effective, safe, and environmentally conscious. The steam distillation method is used to produce the natural combination of essential oils; consequently, the manufacturer opts for harmless materials, minimizing production and operating expenses.
The count of cancers and their associated diseases continues to rise. Recognizing the numerous anticancer drugs available, the ongoing effort to discover a singular drug that demonstrates effectiveness, selectivity, and the ability to surmount multidrug resistance is evident. Therefore, the ongoing quest for strategies to enhance the features of already-employed chemotherapeutic treatments continues among researchers. A conceivable progression is the elaboration of therapeutic approaches focused on particular disease manifestations. By releasing their bioactive agent only under conditions present within the tumor microenvironment, prodrugs enable precise delivery of medication to the targeted cancer cells. click here One method for obtaining such compounds involves attaching a ligand, exhibiting affinity for overexpressed receptors in cancer cells, to a therapeutic agent. Encapsulating the drug within a carrier stable in physiological environments yet responsive to tumor microenvironment conditions presents another viable approach. By attaching a ligand recognized by tumor cell receptors, the carrier can be directed to its target. For targeting overexpressed receptors in cancer cells, sugars present themselves as ideal ligands for constructing prodrugs. Ligands, they can also modify polymer drug carriers. Subsequently, polysaccharides can act as discerning nanocarriers for a considerable number of chemotherapeutic drugs. Numerous studies dedicated to utilizing these substances for the modification and targeted delivery of anticancer agents validate the assertions of this thesis. Examples from this research highlight the use of broadly defined sugars to improve the characteristics of already-used drugs and substances with anti-cancer potential.
Current influenza vaccines focus on highly variable surface glycoproteins; however, these mismatches between vaccine strains and circulating strains frequently reduce vaccine protection. This necessitates the ongoing development of effective influenza vaccines, which can protect against the mutations and adaptations of different influenza virus strains. It has been established that influenza nucleoprotein (NP) is a viable candidate for a universal vaccine, capable of inducing cross-protection in animal models. In this investigation, a mucosal vaccine incorporating the recombinant NP (rNP) and the TLR2/6 agonist S-[23-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxyl-poly-ethylene-glycol (BPPcysMPEG) was formulated. A study compared vaccine effectiveness with the results obtained from parenterally vaccinating mice with the same compound formulation. Mice immunized with two doses of rNP, either solely or combined with BPPcysMPEG, using the intranasal route, demonstrated augmented antigen-specific humoral and cellular responses. click here Moreover, a striking increase in NP-specific humoral immunity, characterized by elevated levels of NP-specific IgG and IgG subclasses in serum, and NP-specific IgA in mucosal tissues, was evident in mice immunized with the adjuvant-containing formulation, contrasted with mice receiving the non-adjuvanted vaccine.