RSC Pharmaceutics最新文献

Gene mutations within cells can lead to cancer, a global health challenge affecting millions worldwide. In combating cancer, various treatments such as surgery, radiotherapy, and chemotherapy have been employed. However, the distinct underlying genetic abnormalities causing the cancer are sometimes not addressed by conventional treatments. Adding to these obstacles, targeted therapy is another continuing challenge in cancer treatment. According to recent reports, phenylboronic acid (PBA)-decorated nanoparticles efficiently transfer genes to the intended location due to their strong affinity for sialic acid (SA), which is typically overexpressed in cancerous cells. These PBA-decorated nanoparticles may connect to cancer cells specifically, which enables them to target and deliver the cargo to cancer cells. Therefore, the present review concentrates on the role of PBA-decorated nanoparticles in gene/drug delivery. It includes a discussion on various boronic acid (BA)-conjugated macromolecules. We begin with an exploration of the chemistry underlying BA and its utility in effective delivery. Furthermore, the review elaborates on its application as a targeting ligand, providing a promising avenue for more precise and effective cancer treatment strategies.

The application of nanotherapeutics is being considered as one of the most sought-after strategies to combat the threat posed by drug resistant bacteria. One promising type of nanotherapeutic is biogenic silver nanoparticles (bAgNPs) generated through exploiting the reducing potential of plant extracts. Herein, bAgNPs were synthesized at pH 7.4 (bAgNPs) and pH 10 (bAgNPs@pH) through green chemistry approaches using an extract of Phyllanthus emblica fruit as a source of reducing agent. The physicochemical properties, antibacterial potential, and biocompatibility of the as-synthesized bAgNPs were determined. The average size of bAgNPs and bAgNPs@pH was 15.3 and 20.1 nm, respectively, and both types of nanoparticles were negatively charged (i.e., ∼−25 mV). The as-synthesized bAgNPs exhibited excellent antibacterial activity against different bacterial strains such as Bacillus subtilis RBW, Escherichia coli DH5a, Salmonella typhi, Hafnia alvei, enteropathogenic E. coli, Vibrio cholerae, and Staphylococcus aureus. The most effective antibacterial activity of bAgNPs and bAgNPs@pH was observed against Hafnia alvei, a Gram-negative bacterium, with a zone of inhibition (ZOI) of ∼24 and 26 mm in diameter, respectively. The nanoparticles exhibited antibacterial activity through damaging the bacterial cell wall, oxidizing the membrane fatty acids, and interacting with cellular macromolecules to bring about bacterial death. Furthermore, bAgNPs showed excellent hemocompatibility against human red blood cells, and there was no significant toxicity observed in rat serum ALT, AST, γ-GT, and creatinine levels. Thus, bAgNPs synthesized using Phyllanthus emblica fruit extract hold great promise as nanotherapeutics to combat a broad spectrum of pathogenic bacteria. Future directions may involve further exploration of the potential applications of biogenic silver nanoparticles in clinical settings, including studies on long-term efficacy, extensive in vivo toxicity profiles, and scalable production methods for clinical use.

Local anaesthetics provide an opioid-sparing alternative for pain management; however, their short-lived analgesic effect necessitates repeat or sustained drug delivery to the target site. Improving drug loading and enhancing physical stability is a challenge when formulating sustained release devices. Here, myristic acid's interaction with bupivacaine and ropivacaine was studied to evaluate whether eutectic formation between these drugs and myristic acid can similarly influence drug crystallization and increase drug loading in poly ethylene-co-vinyl acetate (EVA). Binary mixtures of ropivacaine and bupivacaine with myristic acid were thermodynamically evaluated by differential scanning calorimetry. Fourier transfer infrared (FTIR) spectra of bupivacaine or ropivacaine and myristic acid binary mixtures at different ratios were obtained and synchronous and asynchronous two-dimensional correlation spectroscopy (2DCOS) maps analysed. Stabilizing effects were observed visually by preparing EVA films containing each drug with and without myristic acid. Thermodynamic and spectroscopic studies suggested that both bupivacaine and ropivacaine form a eutectic with myristic acid at the molar ratio of 2 : 3 and 1 : 3, respectively. 2DCOS FTIR analysis revealed hydrogen bonding between the carbonyl and hydroxyl groups of myristic acid and amide carbonyl group of bupivacaine and ropivacaine, respectively, when myristic acid was present in excess. Furthermore, myristic acid transiently stabilized both bupivacaine and ropivacaine in EVA matrices, but crystallization was evident by the 6-month timepoint. Myristic acid forms a eutectic with both bupivacaine and ropivacaine due to hydrogen bonding interaction. Eutectic formation inhibits crystallization and stabilizes bupivacaine and ropivacaine in EVA matrices, for 1 month, however crystallization of both local anaesthetics was evident after 6-months.

Cytarabine, generally used for the treatment of haematological malignancies, has minimal activity in solid tumours. The present work focuses on the evaluation of the cytotoxic efficiency of cytarabine in MCF-7 cell lines with the aid of fucoidan nanoparticles as drug delivery systems. Polyethyleneimine (PEI) crosslinked fucoidan nanoparticles were synthesised by polyelectrolyte complexation and were characterised by FTIR and ¹H NMR. TEM analysis revealed cytarabine-loaded fucoidan nanoparticles (CFNPs) with a size of less than 40 nm. In vitro release kinetics studies showed that the release of cytarabine (82.17 ± 1.24%) from CFNPs was higher at pH 6.4. Molecular simulation studies revealed that fucoidan–cytarabine binding is mainly facilitated by hydrogen bonds. Internalisation of fucoidan nanoparticles by MCF-7 cells was tracked using the fluorophore, SQ 650. Cell viability studies showed improved cytotoxicity in CFNP-treated MCF-7 cell lines compared to free cytarabine. Quantitative real-time PCR showed upregulation of the expression of apoptotic genes, bax, cyt c and cas 9 in cells treated with CFNPs. Flow cytometry using Annexin V/PI displayed an increased percentage of apoptotic cells on treatment with CFNPs compared to cytarabine alone. The result of this study shows that the cytotoxic efficiency of cytarabine in MCF-7 cells can be enhanced using fucoidan nanoparticles as delivery systems.

Inspired by the antifreeze proteins found in the blood of Trematomus borchgrevtnki, a fish from the Antarctic Ocean, herein we developed metal organic framework (MOF) based ‘waterless’ eutectogels with impermeable nano-domains as antifreeze “soft” materials. The eutectogels were successfully developed through dissolving sodium alginate and ZIF-8, a known MOF, within deep eutectic solvents (DESs) prepared from the environmentally benign biocompatible cryoprotectants glucose and fructose as the HBDs and choline chloride as the HBA. The structural integrity of ZIF-8 and DES was preserved during the eutectogel formation and so also their properties. The eutectogels showcased notable attributes, including antifreeze properties, self-healing capabilities, injectability, adhesiveness, substantial drug loading capacity (∼75 000 and ∼71 000 fold higher curcumin than in water) and efficient sustained drug release behaviour. Moreover, the eutectogel also demonstrated antibacterial and antioxidant attributes, along with hemocompatibility evidenced by hemolysis levels below 2%. Furthermore, the eutectogel exhibited biocompatibility even at very high concentrations (50 mg mL⁻¹). Leveraging on its robust colloidal forces and an environmentally benign composition, the studied eutectogel proves its suitability not just for pharmaceutical applications but also for high-performance applications that prioritize ecological sustainability.

In this study, we elucidate the conceptualization and synthesis of hybrid compounds (T1–T18) amalgamating pyrazine and 1,2,4-triazole scaffolds. A total of eighteen compounds were screened in vitro for their efficacy against the Mycobacterium tuberculosis H37Rv strain via the MABA assay. The results revealed that eight compounds (T4, T5, T6, T11, T14, T15, T16, and T18) manifested noteworthy activity against Mtb, with minimum inhibitory concentration (MIC) values of ≤21.25 μM. Furthermore, we also examined these compounds for their antibacterial and antifungal properties against various strains. Compounds T4, T9, T10, T16, and T18 displayed significant antibacterial activity, while compounds T12 and T14 demonstrated significant antifungal activity. Subsequently, the most potent compounds were evaluated for their potential cytotoxicity to the Vero cell line via the MTT assay, revealing IC₅₀ values surpassing 375 μM, indicative of minimal cytotoxicity. Additionally, we conducted in silico studies on these target molecules to better understand their action mechanisms. The in silico investigations suggest that the target enzyme involved in the action of the compounds may be DprE1. However, further experimental validation is necessary to ascertain the target responsible for the whole cell activity. All the target compounds are docked within the active site of the DprE1 enzyme, demonstrating favorable binding interactions. Furthermore, we predicted the ADME properties, physicochemical characteristics, and drug-like qualities of the target compounds using in silico methods. We also performed DFT studies to examine their electronic properties. These findings collectively indicate that the active compounds hold substantial promise as prospective contenders for the development of novel antitubercular agents.

Antimicrobial resistance poses a serious threat to global health, necessitating the exploration of innovative solutions. Antimicrobial nanoparticles have emerged as a promising avenue, exhibiting unique properties by producing superoxide ions and hydroxyl radicals that efficiently kill bacteria. This article takes an in-depth look at state-of-the-art antimicrobial nanoparticles, their types, and modes of action. Metallic, polymeric, lipid, and carbon-based nanoparticles mostly exhibit antimicrobial actions by disrupting membranes, inhibiting enzymes, and producing different types of reactive oxygen species. Despite their promising potential, challenges and concerns surrounding cytotoxicity, biocompatibility, and environmental impact due to the development of resistance demand meticulous consideration and critical evaluation. This raises an urgent need for continuous research efforts, focusing on standardized regulatory outlines and advancements in the tunable synthesis of nanoparticles with optimized balance, large surface area, hydrophobicity, and cationic nature to harness their full potential in controlling antibiotic-resistant bacterial infections and wound management.

Mitonafide-loaded liposomes are a promising strategy to overcome the neurotoxicity observed in clinical trials for this drug. This study investigates the influence of loaded mitonafide or a dimer analogue on different liposomal formulations and their therapeutic efficacy in vitro. Physicochemical properties of the liposomes were manipulated using different loading methods (namely bilayer or core loading) and varying the rigidity of the bilayer using distinct phospholipid compositions. Our results demonstrated that the mitonafide dimer analogue had a comparable encapsulation efficiency (EE%) into the liposomes when loaded into rigid or flexible bilayers in contrast to the low mitonafide monomer EE%. A pH gradient core loading method resulted in a more efficient mechanism to load the monomer into the liposomes. DOSY NMR and spectrofluorometric studies revealed key differences in the structure of the vesicles and the arrangement of the monomer or the dimer in the bilayer or the core of the liposomes. The in vitro assessment of the formulations using MDA-MB-231 and RT-112 cells revealed that a flexible lipid bilayer allows a faster drug release, which correlated well with the spectroscopy studies. This study investigated for the first time that the characteristics of the lipid bilayer and the loading method influence the encapsulation efficacy, colloidal properties, photoactivity and stability of mono and bis-naphthalimides loaded in a liposomal carrier, essential factors that will impact the performance of the formulation in a biological scenario.

Biopolymer nanoparticles have emerged as promising carriers for bioactive agents, offering sustained or controlled release and improved biocompatibility. The purpose of this study was to design novel calcium cross-linked alginate nanoparticles as a delivery system for ferrous ascorbate and folic acid, synthesized through a modified ionic gelation method, to enhance their oral bioavailability. Calcium alginate nanoparticles were successfully prepared using a modified ionic gelation method, and their particle size and zeta potential were characterized. These nanoparticles were then loaded with ferrous ascorbate and folic acid, and successful encapsulation was confirmed using electron energy loss spectroscopy (EELS) and X-ray photoelectron spectroscopy (XPS). The morphology of the loaded nanoparticles was also investigated using electron microscopy techniques. The encapsulation efficiency of ferrous ascorbate and folic acid was determined to be 95 ± 1.9% and 80 ± 0.7%, respectively. In vitro release studies demonstrated that the release of ferrous ascorbate and folic acid from the loaded nanoparticles was pH-dependent, with a slower release rate being observed at pH 7.4 compared to that at pH 2. The release kinetics was found to follow the Korsmeyer–Peppas diffusion model, suggesting a combination of Fickian diffusion and anomalous diffusion mechanisms. Overall, the findings of this study indicate that the alginate nanoparticles have the potential to serve as a promising nano-drug delivery system for ferrous ascorbate and folic acid, potentially improving their oral bioavailability and therapeutic efficacy in the treatment and prevention of anaemia.

Amorphous solid dispersions (ASDs) are a widely studied formulation approach for improving the bioavailability of poorly water-soluble pharmaceuticals. Yet, a complete understanding remains lacking for how specific processing methods may influence ASDs’ molecular structure. We prepare ketoprofen/polyvinylpyrrolidone (KTP/PVP) ASDs, ranging from 0–75 wt% KTP, using five different amorphization techniques: melt quenching, rotary evaporation with vacuum drying, spray drying, and acoustic levitation with either a premixed solution or in situ mixing of separate co-sprayed solutions. The co-spray levitation approach enables on-demand compositional changes in a containerless processing environment, while requiring minimal pharmaceutical material (∼1 mg). The structure of all ASDs are then compared using high-energy X-ray total scattering. X-ray pair distribution functions are similar for most ASDs of a given composition (R_x = 0.4–2.5%), which is consistent with them having similar intramolecular structure. More notably, differences in the X-ray structure factors for the various amorphization routes indicate differing extents of molecular mixing, a direct indication of their relative stability against crystallization. Melt quenching, spray drying, and levitation of premixed solutions exhibit some degree of molecular mixing, while the co-sprayed levitation samples have molecular arrangements like those of KTP/PVP physical mixtures. These findings illustrate how X-ray total scattering can be used to benchmark amorphous forms prepared by different techniques.