AAPS PharmSciTech最新文献

Coronary artery blockage, the most common cardiovascular problem, is often treated with drug-eluting stents (DES). This study aims to address the main limitation of traditional angioplasty therapy. Thus, designing, fabricating, and analyzing a novel drug-eluting polymeric stent using liquid crystal display (LCD) technology may potentially represent an innovative approach to DES in the near future. Therefore, a poly (lactic acid) (PLA) based 3D-printed stent was designed using SolidWorks software and fabricated using the liquid crystal display (LCD) method. The cyclosporine-loaded stent was prepared and analyzed using optical microscopy, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Loading efficiency percentage and release characteristics were estimated. The polymeric stent platform was successfully designed and manufactured using PLA resin. Based on the characterization of cyclosporine eluting stent, a loading efficiency of 48.66 ± 5.92% was estimated through the immersion method. The FTIR and DSC results confirmed molecular interactions between cyclosporine and the PLA-based 3D-printed stent compared with physical mixture formulations. A sustained release profile of cyclosporine was also observed where approximately 50% of the drug was released within the first three hours. The sustained-release profile, characterized by the absence of a burst release, holds significant clinical potential by ensuring consistent therapeutic levels, reducing side effects, and potentially improving patient outcomes. Overall, the study highlights the effectiveness of LCD technology in printing the stent platform using PLA resin. The results demonstrated a significant cyclosporine loading with a sustained release profile without any stent coating procedure.

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Dexamethasone, a glucocorticoid, is used to mitigate UVB radiation-induced skin inflammation. Nevertheless, its continuous use has been linked to adverse effects. Sesamol, a compound with promising pharmacological properties, faces a challenge due to its rapid skin permeation, which limits its effectiveness when administered cutaneously. Consequently, polymeric nanocapsules have emerged as a technological solution to enhance the skin residence time and efficacy of sesamol in topical applications. This study details the preparation of sesamol-loaded ethylcellulose nanocapsule suspensions and evaluates their in vitro cytotoxicity against keratinocyte and fibroblast cell lines using the MTT assay. The results show that while free sesamol reduced the viability of 3T3 fibroblast cells, this cytotoxic effect was mitigated upon nanoencapsulation. In HaCaT cells, only the highest concentration of nanoencapsulated sesamol exhibited a moderate cytotoxic effect. A nano-based hydrogel containing 1 mg/g of sesamol and 2.5% guar gum was formulated for cutaneous application. The hydrogel’s pharmacological efficacy was assessed in an in vivo sunburn model induced by UVB light in Swiss mice, demonstrating that the sesamol-loaded nanocapsules significantly attenuated inflammatory responses, as evidenced by a reduction in ear thickness and polymorphonuclear cell infiltration. Furthermore, ex vivo permeation studies on UVB radiation-injured human skin confirmed that nanoencapsulation markedly reduced the permeation rate of sesamol through the skin’s layers. The hydrogels were also found to be bioadhesive to human skin. In conclusion, the hydrogel containing sesamol-loaded nanocapsules presents a promising therapeutic approach for treating inflammatory skin conditions, including sunburn.

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Methylene blue (MB)-based photodynamic therapy has proven to be effective and promising for the treatment of non-melanoma skin neoplasms. However, the topical application of MB has certain challenges. MB is a cationic and water-soluble molecule. These properties limit its partition and diffusion through the layers of the skin, limiting it from reaching the neoplastic cells at therapeutic concentration. Sodium cholate (CNa), a bile salt, enables ion-pairing with cationic drugs, such as MB, through electrostatic interactions. The complex formed modifies the physicochemical properties of MB, which may enable its partition and diffusion through the layers of the skin. Thus, we proposed to investigate the interaction between CNa and MB as a function of CNa concentration and its effect on the partition coefficient, solubility, skin barrier and skin delivery of MB. Spectroscopic and thermal studies of MB/CNa dispersions suggest intermolecular interactions between MB and CNa. CNa causes an increase in the partition coefficient of MB and reduces its solubility in water. CNa at the concentrations used does not cause significant changes in electrical resistance or the profile of FTIR spectra related to the lipids and the proteins of the stratum corneum. The use of CNa at the critical micelle concentration causes a reduction in the release and cutaneous delivery of MB; and, at a concentration below the critical micelle concentration, it does not significantly influence the release, but promotes the cutaneous delivery of MB.

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Flavonoids are a large class of compounds with a variety of biological activities. Nevertheless, their therapeutic application remains limited due to the generally low water solubility. In the present study, an integrated approach was provided to guide the design of flavonoid co-amorphous systems co-formed with piperine (PIP). Firstly, 7 flavonoid compounds showed good miscibility with PIP from 13 flavonoid candidates. Then, molecular dynamics simulation confirmed hydrogen bond formation between 5 flavonoid compounds (i.e., BAI, HES, ISO, NAR and KAE) and PIP. Herein, 5 flavonoid compounds were successfully co-amorphized with PIP by the melting and quench cooling method, which were proved via PLM, PXRD and DSC measurements. FTIR results showed the potential hydrogen bond interactions between -OH of flavonoid molecules and C = O of PIP molecule in the formed co-amorphous systems, which were consistent with RDF analyses in molecular models. For dissolution tests, 4 co-amorphous systems (i.e., BAI-PIP CM, HES-PIP CM, ISO-PIP CM and NAR-PIP CM) appeared abnormally reduced dissolution compared to their original crystalline counterparts arising from the formation of gels during dissolution, while only KAE-PIP CM displayed significantly enhanced dissolution (5.83-fold of crystalline KAE at 12 h) with long-time supersaturated concentration. Meanwhile, KAE-PIP CM kept physically stable at least 3 months under 25°C and 40°C conditions, and possessed excellent physical stability over individual amorphous components, which was attributed to the stronger intermolecular interaction by higher binding energy analysis. Therefore, this study provides a design strategy to guide the screening of flavonoid co-amorphous systems through combining theory-model-experiment techniques.

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Dual drug approaches are gaining research interest owing to the reduction of drug resistance and additive or synergistic effects in treating fungal infections caused by Candida albicans. The present study includes the combination of ketoconazole (KTC) and eugenol (EGN) co-embedded cubosomes (KTC-EGN-CBs) for the effective treatment of candidiasis.The bio-membrane-typical framework of the cubic phase in CBs can help retain both drugs leading to enhancement of antifungal activity. KTC-EGN-CBs were developed by high-speed homogenization, followed by the probe sonication. The optimized KTC-EGN-CBs depicted lower particle size (138.8 ± 1.03 nm) and PdI (0.260 ± 0.006) with a high entrapment efficiency of KTC (79.73 ± 1.21%) and EGN (90.92 ± 2.53%). Further, KTC-EGN-CBs were loaded into the hydrogel system for ease of topical application. The ex vivo diffusion study depicted the CBs helping the KTC and EGN to exhibit significantly higher permeation and retention owing to the resemblance in cubic structure with the skin. Additionally, the in vitro antifungal study of KTC-EGN-CBs resulted in a higher zone of inhibition when compared to the plain drugs against Candida albicans. Furthermore, the effectiveness of cubosomal formulation was observed in the inhibition of planktonic growth, yeast to hyphal formation, biofilm formation, and ROS production. The antifungal activity of KTC-EGN-CBs was found to be more prominent in the infected silkworm model than the plain KTC-EGN. The cell cytotoxicity study on human keratinocyte cells and the irritation study on the hen's egg test-chorioallantoic membrane assay revealed the non-cytotoxic and non-irritant nature of the prepared cubosomes. In a nutshell, these findings demonstrated CBs as a promising carrier for KTC and EGN to effectively treat candidiasis.

Nanotechnology, based on the utilization of nanoparticles, has revolutionized drug delivery techniques, offering groundbreaking methods for managing and diagnosing intricate ailments over the past four decades. This article aims to underscore how the use of these particles has been used to treat previously incurable diseases such as cancer, Alzheimer’s, and Parkinson’s disease. Recently, the integration of diagnostic imaging and targeted therapy using theranostic nanoparticles has improved cancer treatment precision. Moreover, exosome-based drug delivery has demonstrated high in vivo biocompatibility and antigen-carrying ability during vaccine development. The unique properties of these tiny particles enable their transport to specific locations inaccessible to large drug molecules. The development of these nanodrugs by either encapsulation or adsorption of drugs on particles has allowed the loading of both hydrophilic and hydrophobic drugs. Innovative engineering approaches have enabled the engineering of shear-sensitive nanoparticles for site-targeted drug release, which eliminates the requirement for frequent doses, which is common in conventional drug delivery. Factors such as size, shape as well as surface modification are considered during the top-down and bottom-up approaches for engineering nanoparticle-based systems. However, issues related to scaling up manufacturing, long-term safety, and regulatory approval for these techniques must be resolved. The use of these drug delivery systems offers many therapeutic advantages. This article examines the application of these systems across various medical domains including cancer treatment, infectious diseases, cardiovascular disorders, central nervous system ailments, and ophthalmic conditions. This fusion of nanotechnology with drug delivery has the potential to elevate healthcare standards in the future by introducing innovative frameworks for revolutionizing therapeutic practices.

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Viral infectious diseases have long posed significant challenges to public health, leading to substantial morbidity and mortality worldwide. Recent outbreaks, including those caused by coronaviruses, have highlighted the urgent need for more effective antiviral treatments. Existing therapies, while numerous, face limitations such as drug resistance, toxicity, poor bioavailability, and non-specific targeting, which hinder their effectiveness against new and emerging viruses. This review focuses on the latest advances in nanoplatform technologies designed to enhance drug solubility, provide sustained or targeted delivery, and improve the efficacy of antiviral therapies. Additionally, we explore how these technologies can be integrated with novel strategies like genetic modulation to combat viral infections more effectively. The review also discusses the potential of these innovations in addressing the challenges posed by current antiviral therapies and their implications for future clinical applications.

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Recent and emerging environmental policies have boosted the investigation of pressurized metered-dose inhalers (pMDI) that have a minimal impact on climate change. There is a current move away from existing hydrofluorocarbon (HFC)-based propellants, specifically the hydrofluoroalkane (HFA)-134a and HFA-227ea based pMDI products that are approved for the treatment of asthma and chronic obstructive pulmonary disease (COPD), towards those that use low global warming potential (LGWP) propellants. Changing the propellant to, for example, the less environmentally-damaging HFA-152a, is a focus for many manufacturers. In this paper, we report an innovative approach to developing new pMDI drug products with a LGWP propellant. Moreover, proof of the hypothesis that products containing the current propellant and those using a LGWP propellant can achieve equivalent performance is reported, by showing comparability of a triple combination pMDI (Trimbow®) formulated using the LGWP HFA-152a propellant compared with HFA-134a. This paper will present the use of in silico mathematical modelling, leveraging on Chiesi proprietary Modulite® principles to predict and validate in vitro performances of the drug product under development. Validation is carried out using realistic aerodynamic particle size distribution (rAPSD), a novel approach that offers a more accurate prediction of aerosol distribution by incorporating variations compared to the standard aerodynamic particle size distribution (APSD). Additional in vitro testing validates the prediction of in silico models and confirms good comparability in terms of aerodynamic performance between HFA-152a and HFA-134a, which translates in vivo as evidenced by the preliminary pharmacokinetics (PK) in animal models and the formal clinical PK bioequivalence (BE) studies. (Rony et al. in Pulm Pharmacol Ther 85, 2024).

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Lipid based nanocarriers are a commonly used drug delivery system with cargos ranging from small molecules to complex RNA-based therapies. There are several hypotheses how such carriers can enter the cell, in which organelles they reside, and how they cross or escape the endo-lysosomal system. To provide additional insights, the cell-nanocarrier interplay was visualized exemplarily with lipid-based nanocarriers and macrophage-like cultured cells (J774A.1 cells) using high resolution electron microscopy. Nanocarrier uptake into J774A.1 cells was detectable after the first 15 min by intracellular accumulation of electron-dense material. These accumulations were identified as lysosomes and lipid droplets, indicating complete degradation and a subsequent formation of storage organelles as early as 15 min. Inhibition of lysosomal acid lipase did not block lipid droplet formation, but rather resulted in accumulation of lipid droplets within lysosomes. This suggests that other cellular lipases already degrade acylglycerols before they reach lysosomes. Chloroquine co-treatment allowed visualization of nanocarriers inside endosomal vesicles, multivesicular bodies, and lysosomes.

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The nanofiber technology has recently undergone an unprecedented transformation, finding widespread utilities across diverse scientific disciplines. It is noteworthy that electrospinning approaches have emerged as an adaptable and successful approach to generate fibers ranging in rapidly as a class of therapeutic agents with a high level of target specificity. Peptides encounter several challenges as drugs, including swift breakdown by the body, rapid elimination from the bloodstream, inadequate stability, and restricted ability to cross cell membranes. This renders it challenging to employ them as drugs. However, electrospun nanofibers might address these problems. This review explores the promising potential of electrospinning nanofibers for peptide delivery. We delve into recent advancements in this technique, highlighting its effectiveness in overcoming challenges associated with peptide drug delivery. It provides an analysis of the trends identified in the use of the electrospinning technique and its role in peptide drug delivery systems, based on a review of data collected over a period of five to seven years.

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