RSC Pharmaceutics最新文献

The bilateral relationship between nanomaterials and biological systems can play a significant role in therapeutic interventions and diagnostics. The nanomaterials may lose their synthetic identity after encountering biological fluids (e.g., serum or plasma), and it might lead to unintended outcomes in real-time applications. Despite advances in nanomedicine, clinical translation and overall patient survival using nanoformulations have largely remained elusive. The layer of biomolecules formed around nanoparticles (NPs), often referred to as protein-corona (PC), can impact their physicochemical properties, including size, surface charge/chemistry, chemical composition, solubility, etc. Recently, a few mechanistic evaluations have demonstrated that the formation of a corona layer on nanoparticles can also have a consequential effect on the release profiles of polymeric soft NPs. To evaluate their therapeutic efficacy and resolve discrepancies that exist between in vitro and in vivo results, transition of NPs from their native to the corona-coupled state and its impact on unloading of their cargo need to be understood. Here, we highlight (i) how inherent properties of polymer precursors can affect PC build-up on soft NPs and its impact on cargo-release kinetics and (ii) limitations of existing methods in analyzing PC in complex systems, with emphasis on the impact nano–bio interactions have on the soft nanoparticle-based drug delivery domain.

The current work aims to enhance the solubility, dissolution rate and stability of the poorly water-soluble drug rivaroxaban (RXB) by preparing an amorphous solid dispersion (ASD) of its eutectic with mandelic acid (MA) as an acidic coformer. Eutectics generally have lower melting points compared to their constituents. Hence, they can be used to lower the processing temperature of the drug to prevent its thermal degradation under a hot melt extruder (HME). Six eutectics of RXB were prepared with various carboxylic acid coformers. The eutectic of RXB and MA (1 : 4, mol/mol), which had the lowest melting point, was selected for the HME process. A hydrophilic polymeric matrix was used to prepare the ASD of the selected eutectic. The resultant extruded filament was further subjected to solubility and dissolution studies. We could load up to 25% RXB–MA eutectic in the polymer matrix to yield a complete ASD of RXB–MA at a lower processing temperature of 110 °C. The ASD of the RXB–MA eutectic showed three times the drug release compared to pure RXB. The RXB–MA (1 : 4) eutectic lowered the HME process temperature, further enhancing the thermal stability, solubility and dissolution rate of RXB. The solubility and dissolution rate enhancement might favourably impact the drug's bioavailability.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that primarily affects the synovial joints, causing substantial physical impairment, socioeconomic challenges and, in severe cases, death. Symptoms often appear between the ages of 35 and 60, with varying severity caused by periods of remission and exacerbation. In addition, children under the age of 16 might develop juvenile rheumatoid arthritis (JRA). According to a 2021 CDC poll, the World Health Organization estimates that 14 million people worldwide suffer with RA, with 0.92% of India's adult population afflicted. Non-steroidal anti-inflammatory drugs (NSAIDs), synthetic disease-modifying anti-rheumatic drugs (sDMARDs), and biological DMARDs are among the current therapeutic interventions. However, these therapies frequently exhibit limitations such as systemic side effects, short biological half-lives, erratic absorption, and frequent dosing regimens. Recent advances in ligand-based nanotechnology have introduced ligands such as folic acid and sialic acid that improve the targeted delivery when conjugated with nanoparticles. This approach has demonstrated efficacy in improving therapeutic outcomes while alleviating the side effects associated with conventional drug delivery systems. This review highlights the key molecular targets in RA, including T cells, B cells, and TNF-α, while exploring novel ligand-based active targeting strategies as innovative therapeutic avenues. Furthermore, it gives in-depth insights into critical molecular targets and their corresponding ligands, emphasizing the rising importance of ligand-based nanotechnology in the development of targeted drug therapy for autoimmune illnesses such as RA. The findings show the potential for these technologies to revolutionize RA therapy by improving medication specificity and reducing side effects via precise novel targeting mechanisms.

Nanomedicines offer high promise for the treatment of various diseases, and numerous novel approaches using nanomaterials have been developed over the years. In this report, we introduce a new strategy utilizing ZnO nanoparticles (nZnO) to trigger the rapid release of lipid-encapsulated therapeutics upon photo-irradiation with UV light (365 nm). In vitro studies demonstrate that encapsulation of nZnO effectively eliminates the cytotoxicity of nZnO, but this can be re-established upon release from the lipid coating. Using 5(6)-carboxyfluorescein as a model for hydrophilic drug loading, we show the ability to co-load drugs with nZnO into liposomes. Kinetic studies reveal the ability to release the majority of the dye within 60 minutes post-photo-irradiation and provide insights into factors that impact release kinetics. To further explore this, Jurkat T cell leukemia and T47D breast cancer cells were treated with co-encapsulated nZnO and the hydrophobic cancer drug paclitaxel. These studies revealed enhanced toxicity of the triggered release groups with an extreme difference noted in the viability profiles of the T47D breast cancer cell model. Taken together, these studies indicate that this system of co-encapsulating nZnO and chemotherapeutic drugs has the potential to minimize systemic toxicity, by controlling therapeutic release, while allowing for the localized selective destruction of cancer.

Hydrogels have been widely studied as substrates for drug delivery and tissue engineering owing to their biocompatibility and ability to swell in aqueous media. Encapsulation of lipophilic active pharmaceutical ingredients (API) as crystalline micro-/nanoparticles within hydrogel formulations has shown promise for improving their bioavailability and achieving high drug load. Despite the size reduction of the API within the hydrogel mesh, the bioavailability of these formulations is largely governed by the inherent ability of the hydrogel polymer backbone to release the API. In this work, Michael addition-based Polyethylene glycol (PEG) hydrogels are developed for micro-crystalline fenofibrate (Fen) encapsulation. Using a parallelized step emulsification device, API nanoemulsion (NE) loaded micro-hydrogels are fabricated and subsequently subjected to anti-solvent extraction for API crystallization. The bi-molecular nature of the Michael addition reaction provides modular incorporation of crosslinking functional groups leading to precise temporal control over hydrogel degradation, thereby offering a sensitive handle on the release of micro-crystalline fenofibrate. By merely changing the chemical identity of the hydrogel cross-link, complete Fen release could be tuned from 4 hours to 10 days. Furthermore, the interaction of crystallizing Fen and PEG within the micro-hydrogel environment led to eutectic formation. This unique feature offered a second handle on the Fen release from the composite micro-hydrogels.

This work details the synthesis of five N-benzylated derivatives of thiabendazoles (L1–L5), four of which were previously unreported in the literature (L2–L5). The compounds were characterised using a comprehensive array of spectroscopic (FT-IR, ¹H, ¹³C{1H}, and ¹⁹F{1H} NMR), spectrometric (MS-EI+) and diffractometric (SC-DRX) techniques. To evaluate the effect of increased fluorine substituents in the N-benzyl fragment, we conducted a parasitotoxic activity assay, testing the compounds at various concentrations of unhatched Taenia crassiceps cysticerci. The inclusion of the N-benzyl fragment and the increase in fluorine substituents led to an enhancement in the lipophilicity of thiabendazoles.

Effervescent tablets are solid pharmaceutical dosage forms that are widely accepted due to their advantages. The improvement in patient compliance results from a combination of factors related to both the extrinsic characteristics of the tablet and the effects it produces. An important reason is the possibility of avoiding swallowing whole tablets, as a large part of the population, such as the elderly, children, and dysphagic patients, find it difficult to swallow them. The aim of this investigation is to review the recent literature on the technology and application of effervescent tablets and investigate their added value towards upgrading of such dosage forms and in general of pharmaceutical technology. Special attention is given to the excipients that are used for the design and development of efficacious systems, as well as their added value for the drug release studies having in mind the patients’ unmet needs.

Liposomes, spherical phospholipid vesicles with a unique morphology mimicking that of body cells, have emerged as versatile nanoparticles for drug delivery. Their biocompatibility, low cytotoxicity, targeted delivery, and hydrophobic and hydrophilic characteristics make them stand out over traditional drug delivery systems. Liposomes can be tailored in size, composition, lamellarity, and surface charge, offering a unique level of customization for various applications. Extensive research in liposome technology has led to the development of a wide range of liposomal formulations with enhanced functionalities, such as PEGylated liposomes, ligand-targeted liposomes, and stimuli-responsive liposomes. Beyond their crucial role in cancer treatment, liposomes play a significant role in influenza, COVID-19, cancer, and hepatitis A vaccines. They are also utilized in pain management, fungal treatment, brain targeting, and topical and ocular drug delivery. This review offers insight into the types of liposomes, their composition, preparation methods, characterization methods, and clinical applications. Additionally, it discusses challenges and highlights potential future directions in liposome-based drug delivery.

The chief purpose of the current study is to fabricate nanostructured lipid carrier (NLC)-based gel for localized delivery of repurposed albendazole (ABZ) against skin cancer to reduce systemic and other organ-related side effects and enhance patient compliance. ABZ NLCs were constructed by the melt-emulsification ultrasonication method and optimized using Box-Behnken Design (BBD). The ABZ NLCs were analyzed for mean particle size, % entrapment efficiency (%EE), and zeta potential. Furthermore, an NLC-based gel was developed using optimized ABZ NLCs and the Carbopol-934 gelling agent and characterized for physical properties, viscosity, texture, ex vivo skin permeation, in vitro cytotoxicity, stability, etc. The optimized ABZ NLCs displayed a %EE of 89.85 ± 5.6% and a particle size of 176.5 ± 7.3 nm. The pH of the ABZ NLC-based gel developed using 1.0% w/v of Carbopol-934 was between 5.1 and 6.0. The viscosity of the optimized ABZ NLC-based gel was 6.64 ± 0.67 Pa s. Besides, the NLC-based gel exhibited better and controlled ABZ release at pH 5.5 and 6.8 than the conventional ABZ gel. The ex vivo permeation of ABZ from NLCs and the NLC-based gel was 5.1 and 4.5-fold higher, respectively, than from the conventional gel. Notably, the in vitro cytotoxicity against B16F10 cells of ABZ NLCs was 1.7-fold and 2.2-fold higher than those of pure ABZ and the ABZ NLC-based gel. A negligible cytotoxicity of the developed formulations was seen in normal HaCaT cells (human epidermal cells), signifying the compatibility of these formulations with healthy cells. Moreover, the ABZ-incorporated NLCs and NLC gel remained stable for twelve weeks at 4 ± 2 °C. Thus, the given research concludes that the NLC-loaded gel could be a harmless, efficient, and novel choice to treat skin cancer using repurposed ABZ.

This study addresses the potential use of single-glucose microbial amphiphiles as pohospholipid-free drug carriers. Microbial amphiphiles, also known as biosurfactants, are molecules obtained from the fermentation of bacteria, fungi or yeast and are largely studied for their antimicrobial, cleaning or anti-pollution potential. However, recent understanding of their self-assembly properties combined with their interactions with macromolecules suggests broader potential applications, one being the phospholipid-free formulation of drugs. In this study, we demonstrate that this class of bio-based molecules can be directly used to design colloidally-stable vesicular carriers for hydrophobic drugs, without employing phospholipid supports, and that the actives can be delivered to human cells. In this study, multilamellar wall vesicles (MLWVs) have been synthesised using a microbial glycolipid amphiphile and poly-L-lysine, held together by electrostatic attractive interactions. Curcumin, a highly lipophilic molecule, was used as a natural drug model to evaluate the present colloidal system as a potential nanocarrier. The cell uptake of the curcumin-loaded nanocarriers was significantly higher for HeLa cells (50%) compared to normal human dermal fibroblasts (35%) and THP-1-derived macrophages (20%). The cytotoxic effect of delivered curcumin or other pharmaceuticals (doxorubicin, docetaxel, paclitaxel) was higher in HeLa cells as the cell viability was reduced by 50%.