RSC Pharmaceutics最新文献

This study presents the development of biocompatible polymeric films designed for the sustained release of the β-blocker acebutolol hydrochloride (AH). The films were fabricated using chitosan (CH), a biodegradable biopolymer, in combination with varying concentrations of Averrhoa bilimbi leaf extract (ABE), a natural additive with potential antimicrobial properties. The composite films were characterized using crystallinity, spectroscopic, mechanical, thermal, and morphological analyses. Functional testing included swelling studies, cumulative drug release profiling, cytotoxicity assessments, and microbial resistance assessments. The results indicated that the incorporation of ABE positively influenced the structural, mechanical, thermal and morphological properties, including swelling behaviour, thickness, and drug release kinetics. The film with the lowest ABE concentration showed optimal swelling (∼200%) and the highest drug release (∼25%), along with notable drug loading (∼78%) and encapsulation efficiency (∼19%). The release kinetics followed the Higuchi and Korsmeyer–Peppas models, indicating a non-Fickian diffusion mechanism. Importantly, the AH integrity was maintained throughout the fabrication process, and all the films exhibited excellent biocompatibility (90% cell viability rate). These findings support the feasibility of using CH/ABE films as promising candidates for sustained drug delivery systems. The use of plant-based and biodegradable components underscores the potential of this green strategy in pharmaceutical formulations, contributing to sustainable chemistry and reducing the environmental impact in drug delivery applications.

Transdermal microneedle systems offer a minimally invasive strategy for systemic drug delivery in veterinary medicine. In this study, biodegradable microneedle patches composed of polyvinyl alcohol, collagen, and chitosan were evaluated in pigs for the delivery of two model compounds, fluorescein isothiocyanate–dextran (FITC-dextran, 4 kDa) and flunixin meglumine (FLU). Patches were applied to the ear and neck to assess the influence of anatomical site on systemic absorption. FITC-dextran delivered via a single 50 mg patch on the neck achieved approximately 1.2–1.4-fold higher plasma concentrations than oral administration and ear-applied patches, demonstrating enhanced uptake from vascularized regions. FLU patches applied to the ear produced detectable plasma levels up to 72 h post-application, with a maximum concentration of ∼1.9 μg L⁻¹ at 24–48 h, indicating sustained systemic exposure and reinforcing the potential for long-acting therapy. No adverse tissue responses were observed at application sites, highlighting the safety and tolerability of the patches. Overall, these findings emphasize the importance of anatomical site selection, physicochemical properties, and biocompatibility in optimizing microneedle-mediated transdermal drug delivery for veterinary applications.

The transition from 3D to 4D printing has revolutionized additive manufacturing by introducing dynamic shape-changing capabilities. The limitations of 3D printing have led to the development of 4D printing, which uses ultraviolet light to deposit materials layer-by-layer, creating customizable soft fabric structures that can transform over time in response to external stimuli. The stimuli can be physical, chemical, or biological. Predetermined interaction mechanisms and mathematical modelling, facilitated by tools such as CAD and FEEA, play crucial roles in orchestrating these shape-shifting behaviours. 4D printing has applications in the medical, manufacturing, and educational sectors, with applications extending to adaptive medical implants and devices. Research on 4D printing focuses on various shape alterations, with promising transformative effects on manufacturing processes, medical interventions, and educational tools. As 4D printing progresses, it has the potential to revolutionize industries and provide innovative solutions to complex challenges. The interplay between stimuli and responsive materials, guided by advanced modelling techniques, opens new avenues for unprecedented development. The shift from 3D to 4D printing signifies a paradigm change in additive manufacturing, offering a glimpse into the future, where products dynamically adapt to their environment and user needs.

Gene-editing technology for the treatment of genetic diseases uses a system that delivers clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 as ribonucleoproteins (RNPs) in a faster and more transiently effective manner than other delivery methods that involve gene expression. Lipid nanoparticles (LNPs) are an integral part of technology that is used to deliver Cas9 RNPs, and in recent years the in vivo delivery of RNPs has been achieved. While single-guide RNA (sgRNA) forms complex higher-order structures, which are known to result in the formation of heterogeneous RNPs, the impact on RNP-loaded LNP formulations has been overlooked. The results of this study show that the heterogeneity of sgRNA significantly affects the internal structure, physical properties, and knockout activity of RNP-loaded LNP formulations through changes in molecular weight distribution and RNP charge.

A solid solution of caffeine and theophylline is realized as sulphate salt hydrate. The molecules enter the structure with one and two equivalents of water, respectively, creating a novel type of non-stoichiometric hydrate. The solid solution is more thermally stable and enables an increased dissolution rate in water for caffeine and theophylline than the respective hydrated sulphate salts. In spite of the increase in solubility, the solid solution shows reduced permeability of caffeine through a synthetic skin membrane when tested against a physical mixture of the parent salts.

Messenger RNA (mRNA) therapeutics have emerged as a transformative platform following the success of COVID-19 vaccines. However, the transition from prophylactic vaccination to therapeutic protein replacement presents unique challenges, particularly in dosing precision and sustained protein expression control. This review examines the fundamental amplification effect where single mRNA molecules can produce 10³–10⁶ protein copies depending on construct optimization and cellular context, creating both therapeutic opportunities and dosing constraints that vary significantly across applications. Systematic analysis of peer-reviewed literature (2020–2025) and comprehensive clinical trial database examination reveal that current lipid nanoparticle delivery systems provide limited spatial and temporal control, with protein expression following predictable kinetics: rapid onset (2–6 hours), peak expression (24–48 hours), and exponential decline (7–14 days). Recent clinical evidence demonstrates exceptional efficacy in applications tolerating variable protein expression, including cancer immunotherapy where mRNA-4157 achieved a 44% reduction in recurrence risk versus pembrolizumab monotherapy (HR = 0.56, p < 0.05). However, significant constraints emerge for dose-sensitive applications requiring precise protein levels. Analysis of failure cases, including CureVac's CV9104 prostate cancer vaccine that failed to meet overall survival endpoints in Phase IIb trials, reveals critical design requirements for clinical success. Comparative analysis with AAV gene therapy demonstrates complementary therapeutic niches: mRNA excels in transient applications requiring temporal control, while AAV provides sustained expression for chronic conditions. Clinical translation requires careful selection of applications based on dosing tolerance, with cancer immunotherapy, infectious disease prevention, and transient protein therapies representing optimal use cases, while enzyme replacement therapy and hormone replacement face fundamental constraints with current platforms.

Two novel soluble salts of vinpocetine were prepared through simple and highly sustainable mechanochemical methods. Specifically, water-assisted grinding led to the formation of a crystalline, anhydrous, equimolar salt with p-toluenesulfonic acid, whereas neat grinding produced its amorphous counterpart. The structure of the crystalline salt was elucidated using single-crystal X-ray diffraction, while the ionic nature of the amorphous salt was confirmed by X-ray photoelectron spectroscopy. The large ΔpK_a between p-toluenesulfonic acid and vinpocetine promotes the formation of a stable salt, with strong ionic interactions between the protonated tertiary amine of vinpocetine and the tosylate anion (as also attested by amorphous salt glass transition of about 81 °C). Both salts significantly enhance the saturation solubility of vinpocetine at 37 °C in phosphate buffer, achieving thermodynamic equilibrium in half the time compared to the pure crystalline drug. These findings highlight new opportunities for the development of vinpocetine, a compound with well-documented effects on cerebral circulation, whose broader application has so far been limited by its extremely low aqueous solubility.

In contemporary medicine, nano-based drug delivery systems (NDDS) have become a ground-breaking strategy, offering notable improvements in the regulated and targeted release of medicinal drugs. These systems use nanotechnology to reduce adverse effects, increase therapeutic efficacy, and improve medication absorption. In order to achieve certain drug release patterns and improve patient outcomes, recent developments have focused on the creation and optimization of nanoparticles, liposomes, dendrimers, and micelles, among other materials. With an emphasis on advancements in materials, formulation techniques, and targeting mechanisms, this paper reviews current developments in NDDS. In addition to their challenges, such as toxicity, scaling issues, and regulatory barriers, the potential applications of NDDS in the future, such as gene therapy, customized medicine, and several drug delivery systems, are also reviewed. The development of nanotechnology for drug delivery has enormous potential to transform treatment paradigms in a number of therapeutic domains, such as infectious diseases, cancer, and chronic illnesses.

Hemophilia B, caused by factor IX (FIX) deficiency, remains the best candidate for mRNA-based gene therapy. However, efficient hepatic delivery of mRNA continues to be a significant challenge. In this study, we developed and evaluated berberine-functionalized cationic liposomes as a novel delivery platform for FIX mutant mRNAs. Berberine incorporation enhanced the liposome's membrane fluidity and fusion potential, facilitating improved intracellular delivery and endosomal escape. Six different FIX variants were designed, transcribed, and screened for optimal expression. Our results demonstrate that berberine liposomes significantly enhance hepatocyte transfection and enable sustained FIX production, particularly with the TmL mutant. These findings suggest that berberine-functionalized liposomes represent a delivery strategy for mRNA therapeutics, leveraging the natural liver tropism common to lipid-based systems while aiming to enhance hepatocyte transfection efficiency.

Biofilms are biological barriers produced by a variety of organisms either for defense or because of physiological processes. Many microorganisms produce biofilms to adapt to certain adverse conditions and this has resulted in difficulty in their eradication with antimicrobial agents. There is the increasing menace of antimicrobial resistance (AMR) by bacteria due to the production of biofilms. Specifically, bacterial biofilms are complex surface-delimited microbial structures contained in a matrix of extracellular polymeric substances, which are an obstacle to effective medical treatment of infections caused by these bacteria. Biofilm resistance to antibiotics can lead to persistent infections. Of particular concern are biofilms made from ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), which are bacteria resistant to the action of many antimicrobial agents. Following the emergence of AMR attributed to biofilms, which complicates disease treatment options and increases morbidity and mortality, there is an urgent need to understand the underlying mechanism of the formation of biofilms, their structure and the resistance profiles, strategies, and barrier systems, which have not been sufficiently considered all together. This systematic review can enable the precipitation of findings and control strategies for the development of effective interventions, guide research efforts, and inform clinical practices in handling biofilms. This review focuses on the different characteristics of biofilms, the organization of biofilms, the life cycles, and various models for studying biofilms, as well as the ways through which biofilms can be resistant to antimicrobials. The strategies for biofilm management, the role played by biofilms in clinical practice, and promising paradigms for the assessment of the outcome will also be highlighted. With the knowledge of how biofilms function and their relation to pathogens, life scientists can more effectively develop management plans to eradicate biofilm-related infections and provide better patient care.