RSC Pharmaceutics最新文献

Zeolitic Imidazolate Frameworks (ZIFs) are considered as potential nanocarriers in biomedical applications such as storage and transportation of drugs, due to their low toxicity, high internal load and controlled release. In this work, the adsorption of the anticancer drug 5-Fluorouracil (5-FU) in selected ZIFs is studied by employing a multiscale computational scheme that includes semi-empirical computational techniques, Grand Canonical Monte Carlo (GCMC) and molecular dynamics simulations. Our investigation is based on ZIF-8 which is characterized by pH-sensitive controlled drug release. In order to improve the capacity and the drug interaction with the framework we expanded the parent ZIF-8, by replacing each imidazole linker with 3-(1H-pyrrol-3-yl)-pyridine. 5-FU shows enhanced binding affinity (34 kcal mol⁻¹) in modified ZIF with respect to the parent ZIF-8 (12 kcal mol⁻¹) (PM7). Moreover, GCMC simulations were employed to determine the loading of 5-FU in both ZIF compounds under different thermodynamic conditions and over a wide range of pressures, where it is revealed that the loading for the modified ZIF (2311 mg g⁻¹) is four times higher than the loading for ZIF-8 (560 mg g⁻¹). Moreover, molecular dynamics simulations offer a detailed comparison between the two ZIF materials in aqueous systems and provide deeper insight into their drug-material interactions.

Background: Cervical cancer is the second most commonly diagnosed cancer worldwide and the third leading cause of death among women, with approximately 604 127 new cases being reported in 2020. Conventional treatment methods, such as chemotherapy, radiation therapy, surgery, and hormonal therapy, often face significant challenges, including systemic toxicity and reduced efficacy, particularly in the advanced stages of the disease. The treatment of cervical cancer is further complicated by tumor heterogeneity, resistance mechanisms to chemotherapeutic drugs, and the persistent presence of HPV. However, in recent years, nanotechnological interventions, particularly solid lipid nanoparticles (SLNs), have gained increasing attention owing to their robust potential to effectively deliver chemotherapeutic agents while minimizing systemic toxicity. SLNs present a compelling solution for reducing side effects, enhancing drug solubility, improving stability and bioavailability, and overcoming the limitations and resistance associated with conventional treatment strategies. Methods: To provide the context and evidence, relevant publications were searched on Google Scholar, PubMed, ScienceDirect, Dimensions AI, and EBSCO host, using specific keywords such as “cervical cancer”, “drug loading”, “encapsulation efficiency”, “HPV”, “sustained drug release”, and “solid lipid nanoparticles (SLNs)”. We did not impose any restrictions on the publication date during the selection of papers. However, it is imperative to highlight that the initial reports containing specified keywords began publication in 2013. Conclusion: SLNs represent a promising frontier in drug delivery, particularly within cervical cancer therapeutics, because of their ability to facilitate the targeted delivery of chemotherapeutic agents and genetic materials. The potential of SLNs to encapsulate and protect vital therapeutic compounds presents significant opportunities for developing innovative treatment strategies including DNA and peptide vaccines. However, the lack of approved SLN-encapsulated vaccines for cervical cancer underscores the need for rigorous in vivo research and clinical trials to validate their safety and efficacy. Future studies should not only optimize SLNs for various agents but also explore diverse combination therapies to enhance therapeutic outcomes.

Phenylboronic acid (PBA) and its derivatives have emerged as versatile materials with significant implications in biomedical and industrial applications, particularly for glucose-responsive systems. Their unique saccharide-binding properties, dictated by their tunable pK_a, enable advanced functionalities in drug delivery and biosensing. In diabetes management, PBA-based systems ranging from bulk hydrogels to micro/nanogels and self-assembled micelles offer precise insulin delivery mechanisms that respond dynamically to glucose levels. These materials are further enhanced by their adaptability to diverse routes of administration, including subcutaneous, transdermal, and oral delivery systems. Beyond insulin delivery, multifunctional PBA derivatives combined with glucose oxidase or polymers have been utilized in diabetic wound healing, biosensing, and environment-sensitive therapeutic applications like siRNA and cancer immunotherapy. The integration of PBA into hybrid and dual-responsive platforms continues to expand its utility, paving the way for innovative solutions in personalized medicine and diagnostics. This review explores the chemistry, applications, and future prospects of PBA derivatives, emphasizing their transformative potential in creating responsive, biocompatible, and multifunctional systems for biomedical use.

Polymeric hydrogels have become effective materials in cancer therapy because of their biocompatibility, biodegradability and tunable chattels. This review presents a thorough investigation of the synthesis and medicinal uses of different naturally occurring and synthetic hydrogels, for cancer therapy, mainly via 3D modeling and printing. The exceptional biocompatibility of hydrogels, coupled with their remarkable potential for replicating the intricate extracellular matrix (ECM), positions them as ideal materials for constructing scaffolds used in the synthesis of in vitro 3D tumor constructs. Hydrogels can also be used for 3D printing to treat cancer by aiding in accurate control over the composition of hydrogel scaffolds. 3D modeling and printing play an important role in cancer treatment by enabling drug screening. This review distinguishes itself by integrating a comparative analysis of both conventional and emerging hydrogel systems—including natural, synthetic, and hybrid types particularly designed for 3D bioprinting in cancer modeling. This study paves the path for new researchers to explore cancer treatment by combining hydrogel-based materials with advanced techniques.

Microemulsions are nanostructured and thermodynamically stable systems with a reduced droplet size. They can improve drug absorption and distribution. Babassu oil has been investigated for various therapeutic properties reported by popular use. This work aimed to develop, optimize, and characterize babassu oil-based water-in-oil microemulsions to promote a controlled and uniform release of drugs with different physicochemical properties. The optimal microemulsion composition was investigated through pseudoternary diagrams, with water, surfactant mixture, and oil mixture as vertices. The formulations were characterized based on pH, conductivity, size, polydispersity index, and drug content. In vitro drug release was carried out using multidimensional and unidimensional techniques. An optimum microemulsion contains (w/w): 10% water, 17.8% babassu oil, 26.2% medium-chain triglycerides, 29.7% Span™ 83, 7.1% Tween® 80, and 9.2% Transcutol® HP. Diclofenac sodium (DS), donepezil hydrochloride (DH), and insulin were associated with the dispersed phase of the microemulsion. These formulations presented a droplet size of 26.9 ± 1.9, 22.6 ± 0.4, and 35.5 ± 0.7 nm, respectively. The polydispersity index was <0.1 for all formulations. Microemulsions controlled the outflow of drugs, showing a uniform release compared to the respective controls. It was evidenced that these profiles depend on the features of the molecule associated. According to the selection criteria, most experimental DS and DH release kinetics in water or pH 7.2 fit well with the Gompertz model. In conclusion, a babassu oil-based water-in-oil microemulsion was developed for the first time, optimized, and characterized, supporting further investigation of the formulation as a drug delivery system.

The use of lidocaine (0.3% w/w) for pain management in hyaluronic acid-based soft-tissue injectables has been standard for two decades. Given lidocaine's well-known vasodilatory activity it may contribute to the incidence of post-treatment adverse events including bruising in patients. This study seeks to compare these vasodilatory properties of lidocaine with that of another anaesthetic candidate, mepivacaine. Rat aortic rings and human skin resistance arteries (diameter between 200–400 μm) were mounted on an isolated organ bath or myograph, respectively, and exposed to progressively increasing concentrations of lidocaine or mepivacaine from a solution or released from a gel. The concentration-dependent vascular response and kinetics were systematically compared in tissue originating from 3 biological donors. Additionally, tissue perfusion changes induced by 0.3% w/w anaesthetic solutions were assessed using laser Doppler imaging in rabbit ears. Systematically, lidocaine exhibited a greater vasodilatory activity than mepivacaine in clinically relevant concentration ranges in both animal and human models. In contrast to lidocaine, mepivacaine did not have a significant impact on blood vessel vasodilation. In clinical practice, formulation of hyaluronic acid (HA) injectables with mepivacaine may potentially reduce the risk of common adverse events. This characteristic highlights its potential advantages in the practice of hydrogel injections.

Tyrosinase is a key enzyme that regulates the rate of melanin synthesis, thereby modulating both food browning and skin pigmentation. It has been found that aloin is an effective inhibitor of tyrosinase activity and Fe₃O₄@rGO has remarkable drug-loading capability. In this study, enzyme inhibition kinetics and multispectral techniques were employed to investigate the enzyme inhibitory effect of Fe₃O₄@rGO-aloin nanocomposites and evaluate their anti-browning effect and safety. The binding ability of tyrosinase and aloin was further enhanced by the addition of Fe₃O₄@rGO. The IC₅₀ value of Fe₃O₄@rGO-aloin against tyrosinase was determined to be 2.26 ± 0.15 × 10⁻⁵ mol L⁻¹ with a typical anticompetitive inhibition. The findings suggest that Fe₃O₄@rGO-aloin exhibits a more potent inhibitory effect on tyrosinase compared to aloin. Furthermore, three-dimensional fluorescence, Fourier transform infrared and circular dichroism experiments demonstrated that aloin-loaded Fe₃O₄@rGO nanoparticles induce alterations in the secondary structure and conformation of tyrosinase. This indicates the potential of Fe₃O₄@rGO nanocomposites as candidates for the development of novel tyrosinase inhibitors for the treatment of hyperpigmentation disorders.

Cell-penetrating peptide-based probes for positron emission tomography (PET) are currently being developed for cardiac imaging. Herein, we have conjugated a synthetic 12 amino acids (NH₂-APWHLSSQYSRT-COOH) cardiac targeting peptide (CTP) with a NOTA chelator for ⁶⁸Ga labeling. The [⁶⁸Ga]Ga-NOTA-CTP was synthesized with a decay-corrected radiochemical yield of 68.9 ± 12.8% (n = 13) and molar activity (A_m) of 1.3 ± 0.5 GBq per μmol (n = 13). The tracer was evaluated in healthy and diseased CD1 mice with myocardial infarction following ligation of the left anterior descending artery. PET/CT imaging and ex vivo biodistribution revealed rapid (within 30 min) clearance of [⁶⁸Ga]Ga-NOTA-CTP from the blood through renal and hepatobiliary excretion pathways in both healthy and infarcted animals. The uptake of [⁶⁸Ga]Ga-NOTA-CTP in the heart of healthy and infarcted animals did not show any statistically significant difference for up to 120 min post-injection, but regional differences within healthy and infarcted hearts were detected with [⁶⁸Ga]Ga-NOTA-CTP by PET/CT imaging at early time points post-injection. Within a healthy heart, the left ventricle standardized uptake value (SUV) was lower than the right ventricle SUV at 10–30 min post-injection. This regional difference between the left and right ventricles was absent in the infarcted heart, likely due to post-ligation changes.

We would like to take this opportunity to thank all of RSC Pharmaceutics’ reviewers for helping to preserve quality and integrity in pharmaceutics literature. We would also like to highlight the Outstanding Reviewers for RSC Pharmaceutics in 2024.