Assay and drug development technologies最新文献

As one of the primary causes of illness and death globally, cancer demands novel and potent treatment approaches, which is why lipid nanoparticles (LNPs) have gained attention as a promising delivery system for anticancer drugs with precision and efficacy. The article discusses the salient characteristics of LNPs, such as the lipid components, particle size, polydispersity index, and encapsulation efficiency, followed by strategies that enhance their remarkable drug delivery capabilities. The articles explore LNPs ability to improve the solubility, stability, and bioavailability of various chemotherapeutics, nucleic acids, and immunotherapeutic modalities. It also highlights the recent advancement in surface modification of LNPs, which is essential to improve their effectiveness. Tailored coatings of LNPs improve targeting precision, stability, and biocompatibility; enhancing their transport to boost therapeutic efficacy for cancer targeting. The review summarizes the recent advancements made in using LNPs to treat different forms of cancer and focuses on the most recent clinical studies. Overall, the review highlights that the LNPs can target and treat cancer in a tailored manner through gene therapy, RNA interference, and immunotherapy.

The objective of the present study was to optimize the microwave-assisted synthesis of the acrylamide graft copolymer of Acacia nilotica gum (AM-co-ANG). Furthermore, graft copolymer was used for the formulation of a nanoparticulate system using a novel top to bottom solvent antisolvent technique for the delivery of melatonin. Grafting of ANG was optimized by using 3² factorial design, where concentrations of polymer and monomer (acrylamide) were used as independent variables and swelling index in acidic (0.1 N HCl) and basic (1 N NaOH) pH. Grafted polymers were further used to develop and optimize nanoparticulate system using concentration of the graft copolymer and concentration of drug as independent variables. The size of the nanoformulation and entrapment efficiency were selected as dependent variables. Difference in infrared spectrum and absorbance maxima in the ultraviolet region confirm that grafting has taken place. Porous structure and a higher contact angle confirmed hydrophobic nature of AM-co-ANG as compared with the native polymer. Acrylamide graft copolymers show more swelling in 1 N NaOH as compared with 0.1 N HCl. In vitro toxicity studies in hepatic (HepG2 cell line), brain (SHSY5Y cell line), and skin (HaCaT cell line) cells easily predict that synthesized polymer have no cytotoxicity. The entrapment efficiency ranged from 55.24 ± 1.35% to 73.21 ± 1.83%. A nonlinear correlation was observed between independent and dependent variables, as confirmed by multivariate analysis of variance, surface regression, and the correlation report. The prepared formulations were able to release drug up to 12 h. The regression coefficient easily predicted that most of the formulations followed Baker-Lonsdale drug release kinetics.

Cholangiocarcinoma (CCA) is a prevalent and highly lethal form of cancer globally. Although microRNAs (miRNAs) have been implicated in the advancement of CCA, their potential influence on 5-fluorouracil (5-Fu) resistance in CCA remains to be fully elucidated. Here, in this study, we investigated the impact of miR-22-3p on CCA resistance. Our investigation involved bioinformatics analysis, which revealed an association between miR-22-3p and the progression, diagnosis, and patient survival of CCA. Furthermore, we validated a notable downregulation of miR-22-3p expression in CCA cell lines. Elevated levels of miR-22-3p inhibit the activity and proliferation of 5-Fu-resistant CCA cell lines. In addition, we confirmed that phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a target gene of miR-22-3p, and its expression correlates with the survival of CCA patients. Reduced PTEN expression enhances apoptosis in 5-Fu-resistant CCA cells. Meanwhile, we verified the existence of the miR-22-3p/PTEN/phosphatidylinositol-3 kinase (PI3K)/Protein kinase B (AKT) regulatory networks in CCA, influencing the sensitivity of CCA cells to 5-Fu. In conclusion, our findings suggest that miR-22-3p acts as a tumor suppressor. Its overexpression inhibits the PTEN/PI3K/AKT axis, promoting cell apoptosis and enhancing CCA sensitivity to 5-Fu.

Nanoparticle-based drug delivery systems have emerged as promising platforms for enhancing therapeutic efficacy while minimizing off-target effects. Among various strategies employed to optimize these systems, polyethylene glycol (PEG) modification, known as PEGylation-the covalent attachment of PEG to nanoparticles, has gained considerable attention for its ability to impart stealth properties to nanoparticles while also extending circulation time and improving biocompatibility. PEGylation extends to different drug delivery systems, in specific, nanoparticles for targeting cancer cells, where the concentration of drug in the cancer cells is improved by virtue of PEGylation. The primary challenge linked to PEGylation lies in its confirmation. Numerous research findings provide comprehensive insights into selecting PEG for various PEGylation methods. In this review, we have endeavored to consolidate the outcomes concerning the choice of PEG and diverse PEGylation techniques.

The relentless pursuit of precision medicine has catalyzed the development of molecular and cellular tethered drug delivery systems, a burgeoning field that stands to redefine the paradigms of therapeutic delivery. This review encapsulates the cutting-edge advancements within this domain, emphasizing the engineering of molecular tethers and cellular vectors designed to ferry therapeutics directly to their target sites with unparalleled specificity and efficiency. By exploiting the unique biochemical signatures of disease states, these systems promise a substantial reduction in off-target effects and an enhancement in drug bioavailability, thereby mitigating the systemic side effects that are often associated with conventional drug therapies. Through a synthesis of recent research findings, this review highlights the innovative approaches being explored in the design and application of these tethered systems, ranging from nanotechnology-based solutions to genetically engineered cellular carriers. The potential of these systems to provide targeted therapy for a wide array of diseases, including cancer, autoimmune disorders, and neurological conditions, is thoroughly examined. This abstract aims to provide a succinct overview of the current state and future prospects of molecular and cellular tethered drug delivery systems in advancing the frontiers of precision medicine.