In contrast, nucleic acids circulating in the blood show an inherent instability, with a short half-life. These molecules' passage through biological membranes is blocked by their high molecular weight and significant negative charges. For the successful delivery of nucleic acids, the development of an appropriate delivery strategy is imperative. The burgeoning field of delivery systems has illuminated the potential of gene delivery, enabling the overcoming of numerous extracellular and intracellular obstacles to effective nucleic acid delivery. Consequently, the rise of stimuli-responsive delivery systems has empowered the precise and intelligent release of nucleic acids, enabling precise guidance of the therapeutic nucleic acids towards their intended sites. From the unique attributes of stimuli-responsive delivery systems, diverse stimuli-responsive nanocarriers have been developed. Fabricating gene delivery systems that are intelligently responsive to biostimuli or endogenous triggers, various approaches have been taken, capitalizing on the tumor's physiological variations in pH, redox potential, and enzymatic activity. Light, magnetic fields, and ultrasound, among other external stimuli, have also been utilized to create nanocarriers sensitive to external conditions. Even so, the majority of stimuli-sensitive drug delivery systems are in the preclinical phase, and several significant hurdles, including suboptimal transfection efficiency, safety issues, the intricacy of manufacturing, and off-target effects, require resolution before clinical translation is possible. This review aims to detail the principles underpinning stimuli-responsive nanocarriers, highlighting key advancements in stimuli-responsive gene delivery systems. Current challenges in the clinical application of stimuli-responsive nanocarriers and gene therapy and the corresponding remedies will be underscored to facilitate their clinical translation.
Recent years have witnessed a rise in the accessibility of effective vaccines, yet this has emerged as a public health challenge due to the multiplying pandemic outbreaks, placing the global population's health at risk. Therefore, the synthesis of novel formulations, that generate a potent immune response against certain illnesses, holds significant importance. Nanoassemblies derived from the Layer-by-Layer (LbL) method, which utilize nanostructured materials in vaccination systems, can partially alleviate the issue. The design and optimization of effective vaccination platforms has been significantly enhanced by the recent emergence of this very promising alternative. In particular, the versatile and modular nature of the LbL method offers powerful tools for the synthesis of functional materials, leading to innovative design options for various biomedical tools, encompassing very particular vaccination platforms. Furthermore, the power to modulate the form, size, and chemical makeup of the supramolecular nanoassemblies derived from the layer-by-layer approach facilitates the creation of materials amenable to specific administration channels and boasting remarkably precise targeting capabilities. In this manner, vaccination programs' efficiency and patient satisfaction will improve substantially. This paper offers a general survey of advanced methods in fabricating vaccination platforms based on LbL materials, aiming to showcase the substantial benefits of these systems.
Following the Food and Drug Administration's approval of the initial 3D-printed drug, Spritam, medical researchers are displaying considerable enthusiasm for 3D printing technology. This approach facilitates the development of multiple types of dosage forms, featuring diverse geometrical structures and artistic designs. check details This method's adaptability and affordability, in the form of dispensing with expensive equipment and molds, makes it incredibly promising for quickly generating prototypes of various pharmaceutical dosage forms. However, the burgeoning interest in multi-functional drug delivery systems, particularly solid dosage forms including nanopharmaceuticals, has occurred in recent times, yet transforming them into a practical solid dosage form presents a difficulty for those involved in formulation. inborn genetic diseases The synergistic application of nanotechnology and 3D printing in medicine has provided a framework for overcoming the challenges inherent in fabricating solid nanomedicine dosage forms. This paper is mainly dedicated to a review of recent advances in the design of nanomedicine-based solid dosage forms achieved by employing the technology of 3D printing. The conversion of liquid polymeric nanocapsules and liquid self-nanoemulsifying drug delivery systems (SNEDDS) into solid dosage forms, like tablets and suppositories, is easily accomplished through 3D printing techniques in the nanopharmaceutical field, facilitating personalized medicine tailored to individual patient needs. This current review further emphasizes the potential of extrusion-based 3D printing techniques, including Pressure-Assisted Microsyringe-PAM and Fused Deposition Modeling-FDM, to generate tablets and suppositories containing polymeric nanocapsule systems and SNEDDS, suitable for oral and rectal administration. This manuscript's critical analysis delves into current research on how variations in process parameters affect the performance of 3D-printed solid dosage forms.
Various solid-state dosage forms benefit from the properties of particulate amorphous solid dispersions (ASDs), specifically in improving oral bioavailability and the stability of large molecules. Although spray-dried ASDs possess an inherent characteristic of surface bonding/attachment, including moisture absorption, this hampers their bulk flow and impacts their utility and viability in the context of powder manufacturing, handling, and function. L-leucine (L-leu) coprocessing's impact on the particle surfaces of ASD-forming materials is investigated in this study. Coprocessed ASD excipients of contrasting types, sourced from both the food and pharmaceutical industries, were meticulously scrutinized to determine their efficacy in coformulating with L-leu, focusing on prototype systems. The model/prototype materials consisted of the following ingredients: maltodextrin, polyvinylpyrrolidone (PVP K10 and K90), trehalose, gum arabic, and hydroxypropyl methylcellulose (HPMC E5LV and K100M). In order to prevent substantial differences in particle size during the spray-drying process, the conditions were precisely controlled, thereby ensuring that particle size variations did not play a major role in influencing powder cohesiveness. Each formulation's morphology was examined using the scanning electron microscope. A blend of previously recognized morphological progressions, indicative of L-leu surface alteration, and previously unseen physical characteristics was observed. Using a powder rheometer, the bulk attributes of these powders were scrutinized, encompassing their flowability under conditions of both confinement and no confinement, the sensitivity of their flow rates, and their propensity for compaction. Elevated concentrations of L-leu corresponded with a general enhancement in the flow properties of maltodextrin, PVP K10, trehalose, and gum arabic, as indicated by the data. Different from other formulations, PVP K90 and HPMC formulations encountered unusual problems, offering valuable insight into the mechanistic behavior of L-leu. This study, thus, necessitates further examination of the association between L-leu and the physicochemical properties of co-formulated excipients in the context of future amorphous powder formulation. Analyzing the multifaceted influence of L-leu surface modification on bulk characteristics highlighted the need for more sophisticated tools to fully characterize the phenomenon.
Among its various effects, linalool, an aromatic oil, offers analgesic, anti-inflammatory, and anti-UVB-induced skin damage reduction. The objective of this study was to produce a topical microemulsion system loaded with linalool. Statistical tools of response surface methodology and a mixed experimental design were employed to create a series of model formulations. Four independent variables (oil (X1), mixed surfactant (X2), cosurfactant (X3), and water (X4)) were manipulated to assess their influence on the characteristics and permeation capacity of linalool-loaded microemulsion formulations. This process ultimately led to the development of a suitable drug-loaded formulation. retina—medical therapies The results of the experiment indicated that the droplet size, viscosity, and penetration capacity of the linalool-loaded formulations were significantly responsive to the different ratios of formulation components. The flux of the drug through the formulations, and the amount deposited in the skin, rose substantially, by about 61-fold and 65-fold, respectively, compared to the control group (5% linalool dissolved in ethanol). Following a three-month storage period, the physicochemical properties and drug concentration exhibited no substantial alteration. The skin of rats treated with linalool formulation presented a statistically insignificant degree of irritation, contrasting with the pronounced irritation noted in the skin treated with distilled water. The research findings suggested that specific microemulsion formulations are possible candidates for delivering essential oils topically.
The majority of presently utilized anticancer agents trace their origins back to natural sources, with plants, often central to traditional medicines, abundant in mono- and diterpenes, polyphenols, and alkaloids that exhibit antitumor properties by diverse mechanisms. Disappointingly, a considerable number of these molecules are affected by inadequate pharmacokinetics and a narrow range of specificity, shortcomings that could be overcome by their inclusion in nanocarriers. Cell-derived nanovesicles have garnered significant attention recently, due to their biological compatibility, their lack of immunogenicity, and, most critically, their capabilities for targeted delivery. Although biologically-derived vesicles hold therapeutic potential, industrial production faces a major scalability hurdle, making clinical implementation difficult. Vesicles, conceptually bioinspired through the hybridization of cellular and artificial membranes, boast remarkable flexibility and efficiency in drug delivery.