RSC Pharmaceutics最新文献

Oral drug delivery remains the most favored method of administration due to its convenience and patient compliance. However, the unpleasant taste of certain medications often leads to poor acceptance, particularly among pediatric and geriatric patients. To address this issue, taste-masking (TM) technologies have emerged as effective solutions for improving the palatability of oral drugs. This review provides an overview of the key features of TM technologies, including the properties of materials used, their mechanisms, and applications in drug delivery. Typically, TM materials work by complexing or encapsulating drug molecules to prevent direct interaction with taste receptors, thus mitigating unpleasant flavors and enhancing the overall sensory experience. The review explores a range of materials—both synthetic and natural—and various TM technologies designed to mask bitter taste. Additionally, it discusses the latest methods for assessing the effectiveness of TM and the current regulatory landscape surrounding the use of these technologies in drug delivery.

There is an increasing interest in subcutaneous (SC) delivery as an alternative to the traditional intravenous (IV) for immunotherapies and other advanced therapies. High-concentration formulations of antibodies are needed to meet the limited-volume requirements of subcutaneous SC delivery. Despite this need, there remain challenges in delivering stable and injectable antibodies in these high concentrations. Hydrogel encapsulation of amorphous solid antibodies has been proven to improve the stability and injectability of high-concentration antibody formulations. However, the antibody is quickly released from the hydrogel due to the material's porosity, leading to rapid, uncontrolled drug release kinetics undesirable for the drug's efficacy and safety. In this paper, we propose a dual-network composite hydrogel which leverages interactions between the two polymer networks to achieve controlled release of the antibody. We load the solid form of the antibody at high concentrations within alginate hydrogel microparticles which are then suspended in thermogelling methylcellulose solution to formulate the in situ gelling composite hydrogel. By facile chemical modification of the alginate to tune the microparticles’ gel properties and alginate–methylcellulose interactions, we demonstrate how the composite system can delay release of the drug in a tunable manner and achieve a near-zero order release profile for improved therapeutic efficacy. We show acceptable injectability properties of the composite hydrogel at high antibody concentrations, highlighting the functionalities of dualnetwork encapsulation. We imagine this composite system to be applicable for the sustained delivery of various therapeutic protein forms, especially for high-loading SC formulations.

The increasing prevalence of healthcare-associated infections from multidrug-resistant bacteria presents a growing challenge due to their high transmissibility, and resistance to traditional antimicrobial strategies. In this study, we introduce an innovative dual-mode antibacterial strategy through the development of novel surface coatings on glass substrates, offering a proof-of-concept solution for enhanced infection control. Our approach uniquely combines the light-active methylene blue silane (MBS1) dye with the potent antimicrobial compound dimethyloctadecyl[3-(trimethoxysilyl)propyl] ammonium chloride (QAS) into silica nanoparticles (SNPs) to create multifunctional antibacterial surface coatings. The distinct use of silane-functionalized MB and QA enables strong covalent bonding with silica nanoparticles, while the robust silane chemistry ensures durable adhesion of SNPs to the glass substrates. While MBS1–SNP coatings generated highly hydrophilic (CA = 28°), light-active surfaces, combination of QAS (QA–MBS1–SNP) coating enhanced surface hydrophobicity (CA = 90°) without compromising photokilling efficiency. The antibacterial efficacy of these coatings was rigorously tested against the Gram-negative bacterium Escherichia coli. The synergistic action of MB and QA demonstrated exceptional photokilling performance achieving >99.999% (>5-log reduction) bactericidal activity under white light (∼500 lux, ∼0.0732 mW cm⁻²) and effectively inhibited biofilm formation by up to 80%. The demonstrated efficacy of these coatings highlights their potential for transformative applications in healthcare settings, providing a robust, multifaceted approach to infection control.

Determining the upper limits of drug loading in amorphous solid dispersion (ASD) with sufficient physical stability and release performance is critical for developing ASD-enabled tablets for poorly soluble drugs. Recent studies have highlighted the utility of the polymer overlap concentration, c*, in maintaining the physical stability of ASD formulations. The present work demonstrates the feasibility of effectively developing high drug loaded ASD tablets using the c* concept as a guide, with posaconazole as the model drug. By incorporating various material sparing formulation technologies, a record high 50% POS loaded tablet with adequate manufacturability and satisfactory dissolution performance was developed using 1.5 g of POS within 14 days. Physical stabilities of the ASD and tablet were maintained for at least 6 months under ambient conditions and 1 month at 40 °C.

Polymeric nanoparticles (NPs) are traditionally formulated using batch methodologies that are poorly scalable and require time consuming, hands-on purification procedures. Here, we prepared poly(lactic acid) (PLA)-based polymeric NPs using a scalable microfluidics-based method and systematically investigated the impact of purification method (centrifugation versus tangential flow filtration (TFF)) to remove poly(vinyl alcohol) (PVA) on macrophage uptake, anti-inflammatory effects, biodistribution, and protein corona formation. TFF purification demonstrated significantly higher recovery of NPs compared to the centrifugation method, with little-to-no aggregation observed. PVA removal efficiency was superior with centrifugation, although TFF was comparable. NP cellular association, in vitro anti-inflammatory activity, and in vivo biodistribution studies suggested purification method-dependent alterations, which were correlated with protein corona profiles. This study underscores the potential of TFF, combined with microfluidics, as an efficient and high-yield purification method for NPs, and reveals the need for extensive confirmation of NP biological activity alongside physicochemical properties when developing NP therapeutics at-scale.

Multilayered nanofibrous scaffolds (MNSs) obtained by electrospinning have gained widespread attention owing to their control over the delivery of drugs. However, polymer and drug solubility issues in common solvent systems still limit their applications. The present work employed acetic acid : water : ethyl acetate (4 : 4 : 2 v/v/v) as a common solvent system for dissolving gelatin and heparin sodium (HS). A GL 20% w/v solution showing optimum viscosity and conductivity, and high encapsulation (89.2 ± 2.13%) was selected. Additionally, TPGS-1000 incorporated in GL reduced the surface tension for better electrospinning and additional free-radical scavenging activity (∼6 fold of blank nanofibers). The central layer was surrounded by upper and lower PCL–GL layers to control the release of the hydrophilic drug (HS). The electrospun PCL : GL layer sustained the release for ∼24 hours. The developed multilayered nanofibrous scaffolds showed accelerated wound healing in a diabetic rat model. Histological analysis of the wound confirmed the accelerated re-epithelialization and reduced inflammatory response. Laser Doppler flowmetry further showed a significant improvement in the blood flow at the wound site at day 14 and day 21, revealing neovascularization. Therefore, the developed multilayered nanofibrous scaffolds provided a plausible method for fabricating regenerative scaffolds for drug delivery and diabetic wound healing.

A novel, fast and optimized etiquette for the production of silver nanoparticles using the root extract of Cyphostemma adenocaule (CA) is reported in our study. This plant is known to possess many natural terpenes, glycosides and sterols, which can reduce AgNO₃ solution. Typical physiochemical analyses like UV-spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (XRD), and Fourier transformed infrared spectroscopy (FTIR) were used to characterize and confirm the synthesis of the produced nanoparticles. The XRD and TEM analyses validated that the obtained particles were spherical shaped with the average size of 18 nm. The CA–AgNPs depicted excellent anti-bacterial activity against the studied gram (+ve) and (−ve) microorganisms and showed a very good S. aureus biofilm in a dose-dependent response (a maximum inhibition of 88% at a 125 μg mL⁻¹ dose). Further results proved its ability to neutralize ABTS free radicals (96.5% neutralization was noted at a 200 μg mL⁻¹ dose with the IC₅₀ value of 48.62 μg mL⁻¹) and mushroom tyrosinase enzyme (tyrosinase is the enzyme responsible for hyperpigmentation) inhibition from 34.25% ± 3.68% to 90.90% ± 3.45%, with the highest activity at 100 μg mL⁻¹. The above results indicate the potential of silver nanoparticles as antibacterial and antioxidant agents and tyrosinase inhibitors in the food, cosmetics and medicinal industries.

In recent years, researchers have extensively studied nanomaterials for plasmonic photothermal therapy (PPTT), with most of the research focused on those active in the near-infrared I (NIR I) window (λ = 650–950 nm). However, there is growing interest in developing nanomaterials that are active in the near-infrared II (NIR II) region (λ = 950–1300 nm) due to the better penetrability and higher tolerance limit of NIR II light by human skin. In this study, the potential of gold nanocapsules (Au Ncap) with a rattle-like structure, consisting of a solid gold bead core and a porous, thin, rod-shaped gold shell was investigated for PPTT. Specifically, the targeted in vitro photothermal activity of Herceptin-conjugated gold nanocapsules that are active in both the NIR I and II regions are explored towards the Her2 positive SK-BR-3 breast cancer cell line. The conjugation of SH-PEG and Herceptin molecules on the surface of gold nanocapsules was validated through a detailed X-ray photoemission spectroscopy (XPS) analysis. The Au Ncap exhibited high photothermal conversion efficiency of 38.6% and in vitro PPTT results showed its excellent cytotoxicity against the SK-BR-3 cell line leading to apoptotic cell death. These findings suggest that this nanostructure can serve as an efficient photothermal agent in the NIR II region showing excellent PPTT activity at a low laser power density of 0.5 W cm⁻².

Controlling the solid-state stability of co-amorphous drug delivery systems has been an ongoing challenge in the pharmaceutical field to date. The main route to stabilise co-amorphous systems is to increase excipient load either in the co-amorphous formulation or via an additional excipient, creating a ternary amorphous system. Increasing excipient load in a formulation can have disadvantages such as producing large oral dosage forms. In this work, the impact of spray drying process parameters on the formation and short-term stability of a drug–drug co-amorphous mixture in the absence of any excipients is investigated. A 9-point design of experiments (DoE) was conducted to assess the impact of atomising gas flowrate and feed flowrate on the co-amorphous formation and stability. It was found that when the outlet temperature was fixed at 50 °C, the atomising gas flowrate had a more significant effect on the physical stability of the co-amorphous mixture than the feed flowrate. Monitoring the stability of formulations at accelerated stability conditions (40 °C per 75% relative humidity) showed that the co-amorphous systems produced at higher atomising gas flowrates, with smaller droplet sizes and subsequent particle sizes, exhibited a higher stability than those produced at lower atomising gas flowrates. Co-amorphous systems produced at the higher atomising gas flowrates remained stable for the 3-month stability testing period demonstrating that the co-amorphous physical stability can be controlled by optimising the spray drying process. The results presented in this study have significant implications for producing co-amorphous drug delivery systems with a high physical stability without the addition of excipients by spray drying.

We describe the formation of a multidrug salt comprising sulbactam (SUL, β-lactamase inhibitor) and amantadine (AMNH, antiviral). Physicochemical investigation of the SUL·AMNH salt revealed enhanced thermal stability compared to pristine starting materials. In vitro studies found that salt formation in SUL·AMNH does not disrupt antibacterial activity against model organisms Escherichia coli and Staphylococcus epidermidis. To our knowledge, we show the first β-lactamase inhibitor-antiviral salt where both components have been approved by the U.S. Food and Drug Administration (FDA), and the first multicomponent solid containing SUL. We envisage our strategy could inspire the design of multicomponent solids for antimicrobial combination therapies.