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The growing knowledge on several classes of non-coding RNAs (ncRNAs) and their different functional roles has aroused great interest in the scientific community. Beyond the Central Dogma of Biology, it is clearly known that not all RNAs code for protein products, and they exert a broader repertoire of biological functions. As described in this review, ncRNAs participate in gene expression regulation both at transcriptional and post-transcriptional levels and represent critical elements driving and controlling pathophysiological processes in multicellular organisms. For this reason, in recent years, a great boost was given to ncRNA-based strategies with potential therapeutic abilities, and nowadays, the use of RNA molecules is experimentally validated and actually exploited in clinics to counteract several diseases. In this review, we summarize the principal classes of therapeutic ncRNA molecules that are potentially implied in disease onset and progression, which are already used in clinics or under clinical trials, highlighting the advantages and the need for a targeted therapeutic strategy design. Furthermore, we discuss the benefits and the limits of RNA therapeutics and the ongoing development of delivery strategies to limit the off-target effects and to increase the translational application.

Partition coefficient (log P ) is a key physicochemical characteristic of lipophilic drugs which plays a significant role in formulation development for oral administration. Lipid-based formulation strategies can increase lymphatic transport of these drugs and can enhance bioavailability many folds. The number of lipophilic drugs in pharmacopoeias and under discovery are continuously increasing and making the job of the formulation scientist difficult to develop suitable formulation of these drugs due to potent nature and water insolubility of these drugs. Recently, many natural and synthetic lipids are appearing in the market which are helpful in the development of lipid-based formulations of these types of drugs having enhanced solubility and bioavailability. One such reason for this enhanced bioavailability is the accessibility of the lymphatic transport as well as avoidance of first-pass effect. This review discusses the impact of lipophilicity in enhancing the intestinal lymphatic drug transport thereby reducing first-pass metabolism. The most appropriate strategy for developing a lipid-based formulation depending upon the degree of lipophilicity has been critically discussed and provides information on how to develop optimum formulation. Various formulation strategies are discussed in-depth by classifying lipid-based oral drug delivery systems with case studies of few marketed formulations with challenges and opportunities for the future of the formulations.

The current study was aimed to develop an amphiphilic drug-lipid nano-complex of rutin:egg phosphatidylcholine (EPC) to enhance its poor absorption and bioavailability, and investigated the impact of the complex on hepatoprotective and antioxidant activity. Rutin nano-complexes were prepared by solvent evaporation, salting out and lyophilisation methods and compared for the complex formation. For the selected lyophilisation method, principal solvent DMSO, co-solvent ( t -butyl alcohol) and rutin:EPC ratios (1:1, 1:2 and 1:3) were selected after optimisation. The properties of the nano-complexes such as complexation, thermal behaviour, surface morphology, molecular crystallinity, particle size, zeta potential, drug content, solubility, in vitro stability study, in vitro drug release, in vitro and in vivo antioxidant study, in vivo hepatoprotective activity and oral bioavailability/pharmacokinetic studies were investigated. Rutin nano-complexes were developed successfully via the lyophilisation method and found to be in nanometric range. Rutin nano-complexes significantly improved the solubility and in vitro drug release, and kinetic studies confirmed the diffusion-controlled release of the drug from the formulation. The nano-complex showed better antioxidant activity in vitro and exhibited well in vitro stability in different pH media . The in vivo study showed better hepatoprotective activity of the formulation compared to pure rutin at the same dose levels with improved oral bioavailability. Carbon tetrachloride (CCl 4 )-treated animals (group II) failed to restore the normal levels of serum hepatic marker enzymes and liver antioxidant enzyme compared to the nano-complex-treated animals. The results obtained from solubility, hepatoprotective activity and oral bioavailability studies proved the better efficacy of the nano-complex compared to the pure drug.

mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.

In this study, an optimized nanostructured lipid carriers (NLCs) were developed and investigated for improving the solubility and oral availability of 6-Gingerol (6G), an active and abundant component of ginger with limited applications due to its poor water solubility plus oral biological availability. The NLCs consisted of a solid lipid (glyceryl monostearate), another liquid lipid (decanoyl/octanoyl-glycerides) and mixed surfactants (Tween 80 and Poloxamer 188), and was prepared by high pressure homogenization method. The optimal 6G-NLC formulation was evaluated through physical properties such as appearance, mean particle size, zeta potential, encapsulation efficiency, and in vitro drug release, alongside techniques viz. , transmission electron microscopy (TEM), differential scanning calorimetry (DSC), as well as powder X-ray diffraction (XRD). Pharmacokinetics were also evaluated in rats. The 6G-NLCs prepared with optimal formulation exhibited a homogenous spherical shape with mean particle size and zeta potential of 63.59 ± 5.54 nm and − 12.18 ± 1.06 mV. Encapsulation efficiency and drug loading were 76.71 ± 1.11 and 1.17 ± 0.35%, respectively. In vitro release profile of 6G from NLCs was sustained and fitted with Weibull equation. After oral administration of the 6G-NLCs, drug concentrations in serum, MRT, and AUC 0-t were significantly higher as compared with the free 6G suspension. All these results indicated that the developed NLC formulation could be effective and promising drug carriers to improve the water solubility of 6G while sustaining the drug release as well as prolonging in vivo acting time of the drug coupled with oral bioavailability enhancement.

Plant‐derived extracellular vesicles (EVs) are promising therapeutic agents owing to their natural abundance, accessibility, and unique biological properties. This review provides a comprehensive exploration of the therapeutic potential of plant‐derived EVs and emphasizes their anti‐inflammatory, antimicrobial, and tumor‐inhibitory effects. Here, we discussed the advancements in isolation and purification techniques, such as ultracentrifugation and size‐exclusion chromatography, which are critical for maintaining the functional integrity of these nanovesicles. Next, we investigated the diverse administration routes of EVs and carefully weighed their respective advantages and challenges related to bioavailability and patient compliance. Moreover, we elucidated the multifaceted mechanisms of action of plant‐derived EVs, including their roles in anti‐inflammation, antioxidation, antitumor activity, and modulation of gut microbiota. We also discussed the impact of EVs on specific diseases such as cancer and inflammatory bowel disease, highlighting the importance of addressing current challenges related to production scalability, regulatory compliance, and immunogenicity. Finally, we proposed future research directions for optimizing EV extraction and developing targeted delivery systems. Through these efforts, we envision the seamless integration of plant‐derived EVs into mainstream medicine, offering safe and potent therapeutic alternatives across various medical disciplines. This review provides a comprehensive review of the state‐of‐the‐art treatment for diseases using exosomes derived from plant. By understanding the composition of exosomes, methods of administration, and their clinical applications, the aim is to explore their therapeutic potential and establish a basis for improving health.

As an irreversible small-molecule kinase inhibitor, ibrutinib (IBR) exhibits excellent tumor suppression in various tumor cells. However, IBR is insoluble at neutral pH and can dissolve only at low pH: thus, commercial IBR products present poor bioavailability and weakened in vivo antitumor activity. Therefore, we aimed to develop a stable IBR-phospholipid complex (IBR-PC) using egg phosphatidylglycerol (EPG) as excipients to improve the bioavailability of IBR and further enhance its antitumor effects. IBR-PC was characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XPRD), and molecular docking and simulation test, which all explained the interactions of two components. Solubility tests demonstrate that the novel formulation can maintain excellent solubility (above 5 mg/mL) at various pH levels. Storage stability tests show that no change in particle size or content of IBR-PC was observed during the experimental period. In vivo pharmacokinetic results demonstrated that the relative bioavailability of IBR-PC was a 9.14-fold improvement relative to that of IBR suspension (IBR-susp). Furthermore, IBR-PC was associated with enhanced cytotoxic activity in vitro and superior tumor growth suppression in vivo compared to that resulting from the free IBR. Thus, the proposed IBR-PC system is a promising drug delivery system that enhances the oral bioavailability of IBR, resulting in its improved in vivo antitumor effect.

Chimeric antigen receptor T cell denoted as CAR-T therapy has realized incredible therapeutic advancements for B cell malignancy treatment. However, its therapeutic validity has yet to be successfully achieved in solid tumors. Different from hematological cancers, solid tumors are characterized by dysregulated blood vessels, dense extracellular matrix, and filled with immunosuppressive signals, which together result in CAR-T cells’ insufficient infiltration and rapid dysfunction. The insufficient recognition of tumor cells and tumor heterogeneity eventually causes cancer reoccurrences. In addition, CAR-T therapy also raises safety concerns, including potential cytokine release storm, on-target/off-tumor toxicities, and neuro-system side effects. Here we comprehensively review various targeting aspects, including CAR-T cell design, tumor modulation, and delivery strategy. We believe it is essential to rationally design a combinatory CAR-T therapy via constructing optimized CAR-T cells, directly manipulating tumor tissue microenvironments, and selecting the most suitable delivery strategy to achieve the optimal outcome in both safety and efficacy. [Display omitted] •Basic information on solid tumor microenvironment and CAR-T therapy is provided.•The current dilemma in CAR-T for solid tumor treatment is summarized.•Rational design strategies of CAR-T therapy including CAR design, TME modulation, and delivery strategies are overviewed.•Combinatory adjuvant strategy for the patient-specific treatment of CAR-T therapy is introduced.

Epigenetic modifications regulate gene expression at the transcriptional level, contributing to tumorigenesis and progression. While epigenetic-targeted combination therapies have gained prominence in oncology treatment management, their clinical efficacy remains constrained by differences in pharmacokinetics and biodistribution among combined agents. Nano-drug delivery systems (NDDS) demonstrate unique potential through co-delivery of therapeutic agents and optimization of their pharmacokinetic profiles. Furthermore, the development of multifunctional NDDS opens new possibilities for precision modulation in cancer treatment, offering valuable insights for clinical translation. Here, this review first outlined the intervention mechanisms of epigenetic dysregulation and analyzed the applications of epigenetic combination approaches. Subsequently, we highlight the transformative potential of NDDS in epigenetic combination therapy, with particular emphasis on how multifunctional NDDS design enables precise therapeutic regulation. This comprehensive analysis aims to advance the clinical translation of epigenetic-based combination strategies through innovative drug delivery solutions. In the future, with the continuous development of AI-driven NDDS design, biomimetic carriers, and dynamic epigenetic editing tools, it will be possible to overcome the clinical challenges of NDDS, enabling truly personalized cancer treatment.

PurposeWith the vigorous development of the e-commerce delivery service industry, delivery service has become an important factor for e-tailers to obtain the market competitive advantage. However, how to choose the best delivery service strategy is a difficult problem for e-tailers in practice. The purpose of this paper is to investigate the effect of delivery service on e-tailers and online platforms.Design/methodology/approachBased on the Stackelberg game, the research study establishes and solves three models, namely dual self-supporting delivery service model, dual third-party delivery service model and differential delivery service model.FindingsThe results show that when the self-supporting and third-party delivery cost coefficients are all small, no matter which delivery service providers the competitor selects, the e-tailer selects delivery with a lower service fee. When the self-supporting and third-party delivery service fee are all low, no matter which delivery service providers the competitor selects, the e-tailer selects delivery with a smaller service cost. Both service fee and service cost determine the choice of e-tailers' delivery strategy. When the commission rate is moderate, both e-tailers are willing to choose the self-supporting delivery strategy, but the platform only prefers to provide self-supporting delivery to them with a lower delivery service sensitivity coefficient.Originality/valueThis paper analyzes the optimal delivery service strategies for e-tailers to compete with competitors, and explores the impacts of parameters for e-tailers and online platforms in their decision-making. The findings provide valuable implications for relevant practices.