Current Drug Delivery - Online First

One of the least invasive, recognized potential routes for both local and systemic drug delivery and the most patient-friendly methods of administering therapeutic agents is transdermal drug delivery. It minimizes gastrointestinal side effects, prevents hepatic first-pass metabolism, lowers dosage frequency, and boosts patient compliance.

This review aims to examine the nanostructured systems for transdermal drug delivery, focusing on their types, design, development and mechanism in enhancing drug permeation through the skin.

This review article synthesized findings from recent studies on nanostructured systems used in transdermal drug delivery systems. With a particular focus on offering a comprehensive understanding of transdermal drug delivery methods and augmentation strategies, the author examines current trends and potential uses of transdermal technologies.

Nanostructured systems have shown increased drug penetration, improved bioavailability and controlled release profiles.

Nanostructured systems offer a versatile and effective approach to overcoming the limitations of traditional transdermal drug delivery methods. Future research should focus on optimizing these systems for clinical applications, ensuring safety and regulatory compliance.

Renal fibrosis is recognized as the final common pathway of chronic kidney disease (CKD) progression, ultimately leading to end-stage renal failure and defined by excessive accumulation of extracellular matrix (ECM) by renal myofibroblasts in the interstitium. To establish an effective drug delivery system targeting fibrotic lesions, we developed nanoparticles modified with short-chain peptides that bind type IV collagen (Col IV), a distinct ECM component remodeled in fibrosis.

Col IV-targeting nanoparticles were intravenously administered to a unilateral ureteral obstruction (UUO) rat model of renal fibrosis. The distribution of these nanoparticles to the renal interstitium was examined via fluorescence-based ex vivo imaging and analysis of frozen kidney tissue sections. Additionally, we assessed cellular uptake in renal fibroblasts (NRK-49F), with or without transforming growth factor-beta 1 (TGF-β1) stimulation, using flow cytometry.

Both Col IV-targeting and non-targeting nanoparticles exhibited increased distribution in the fibrotic renal interstitium compared to healthy tissue. Moreover, the Col IV-targeting nanoparticles localized more extensively in the fibrotic interstitium than their non-targeting counterparts. In vitro, Col IV-targeting nanoparticles also showed significantly higher accumulation in NRK-49F cells, irrespective of TGF-β1 stimulation, compared to non-targeting nanoparticles.

In a UUO-induced renal fibrosis model, these nanoparticles efficiently migrated to the fibrotic renal interstitium, and in vitro experiments using NRK-49F cells demonstrated enhanced uptake by renal fibroblasts and myofibroblasts, central mediators of ECM deposition in fibrotic progression.

We successfully fabricated and evaluated Col IV-targeting nanoparticles, which may serve as an effective drug delivery platform for antifibrotic therapies, potentially mitigating CKD progression.

The interaction of the kidneys with nanoparticles is a fundamental issue that accelerates the proper design of efficient and safe nanotherapeutics. The present study aimed to establish the kidney toxicity and the biodistribution profile of novel gold and silver nanocluster formulations.

Gold and silver nanoclusters were synthesized in an albumin template to probe their kidney-nano interaction. The interaction was performed on healthy animals to unveil the toxicity of nanoclusters on kidney tissue.

Albumin-based gold nanoclusters (BSA-AuNCs) and albumin-based silver nanoclusters (BSA-AgNCs), exhibited comparable core size (2.2±1.3 nm and 2.5±1.6 nm, respectively) and hydrodynamic diameter (11.3±2.1 nm for BSA-AuNC and 10.7±1.9 nm for BSA-AgNC) indicating similarity in their core and overall sizes. Zeta potential measurements demonstrated a comparable surface charge between BSA- AuNC (18.1±3.2 mV) and BSA- AgNC (20.1±3.6 mV), which closely resembled the surface charge of albumin in water (20.7±3.5 mV). Upon administration to rats via intravenous route, ICP-OES measurements showed a significant silver and gold nanocluster accumulation in various vital organs with unequal distribution patterns. BSA-AgNC exhibited higher concentrations in the liver and spleen, while BSA-AuNC showed predominant accumulation in the liver and kidneys. However, the administered BSA-AgNC induced more renal damage than BSA- AuNCs.

The identified renal toxicity linked to BSA-AgNCs, despite their lower kidney accumulation than BSA-AuNCs, illuminates the intricate interplay between nanoparticle biodistribution and toxicity. This underscores the significance of considering the core metal type in nanoparticle design and evaluation. Further investigation is needed to clarify the underlying molecular mechanisms of the observed biodistribution and toxicity.

The primary aim of this study was to develop an effective treatment strategy for periodontal diseases that maximizes therapeutic effects while minimizing systemic adverse effects. Specifically, the study focused on creating a xerogel-based localized drug delivery system for the slow release of doxycycline hyclate (DH) to treat periodontal disease.

Xerogels were prepared using the solvent casting method, with the solvent being evaporated slowly at ambient conditions. The prepared DH xerogels underwent comprehensive characterization to assess their in-silico compatibility, pharmacokinetics, and physicochemical properties. The properties studied included drying time and rate, thickness, moisture content, swelling index, organoleptic properties, scanning electron microscopy, FTIR spectroscopy, differential scanning calorimetry, drug release and kinetics, and antibacterial activity.

In-silico studies demonstrated compatibility between the ingredients, indicating minimal adverse effects on the body. The analysis revealed hydrogen bonding between the drug and polymers, changing the drug's crystallization characteristics to an amorphous form. The release profiles of DH from the xerogels indicated a slow release, ranging from 29.42% to 66.30% over 10 hours, following the Hopfenberg model.

The findings of this study suggest that the formulated xerogels are well-suited for periodontal applications. The slow-release profile of DH from the xerogels offers a promising approach for localized treatment of periodontal disease, reducing the risk of systemic adverse effects. This data is valuable for dental practitioners and pharmaceutical formulators, providing a new avenue for enhancing periodontal disease treatment.

Influenza, a seasonal infectious disease, has consistently posed a formidable challenge to global health in recent years. Favipiravir, an RNA-dependent RNA polymerase inhibitor, serves as an anti-influenza medication, currently administered solely in oral form for clinical use. However, achieving an effective therapeutic outcome often necessitates high oral doses, which can be accompanied by adverse effects and suboptimal patient adherence.

To enhance favipiravir delivery efficiency and potentially mitigate dosage-related side effects, this study aimed to formulate favipiravir as a dry powder for pulmonary inhalation, facilitating direct targeting of lung tissue.

Employing L-leucine as a carrier, favipiravir was prepared as an inhalable dry powder through the spray-drying technique. A 3x3 full-factorial design approach was adopted to optimize the formulation. The optimized spray-dried powder underwent comprehensive characterization, including assessments of its morphology, crystallinity, flowability, and aerodynamic particle size distribution. The therapeutic efficacy of the powder was evaluated in a mouse model infected with the H1N1 influenza virus.

The formulated powder demonstrated good aerosol properties, rendering it suitable for inhalation delivery. Its therapeutic efficacy was demonstrated in the mouse model, where it exhibited marked protective effects against the virus in vivo after 5 days of treatment. Notably, the inhalation dose required (15 mg/kg/day) was significantly lower than the oral gavage dose (150 mg/kg/day), indicating that substantially reduced doses, when administered via inhalation, were sufficient to confer protection against mortality in mice.

The findings underscore the potential of inhalation therapy using spray-dried favipiravir powder as an effective and efficient treatment option for influenza, offering the promise of reduced dosing requirements and associated adverse effects.

Plant-derived extracellular vesicles (PDEVs) are vital for intercellular material exchange and information transfer. They significantly regulate cellular functions, tissue repair, and self-defense mechanisms.

This review summarizes the formation pathways, composition, and potential applications of PDEVs in anti-tumor research and drug delivery systems.

We conducted a literature search using keywords such as “plant-derived extracellular vesicles,” “exosomes,” “drug delivery,” “isolation and purification,” “stability,” “anti-tumor,” and “tumor therapy” in databases including PubMed, Web of Science, and Scopus. We examined studies on the formation pathways of PDEVs, including fusion of multivesicular bodies with the plasma membrane, exosome-positive organelles, and vacuole release. We also reviewed isolation and purification techniques critical for studying their biological functions. Furthermore, we analyzed research on the application of PDEVs in cancer therapy, focusing on their inhibitory effects in various cancer models and their role as carriers in drug delivery systems.

PDEVs have demonstrated potential in anti-tumor research, particularly with vesicles from plants like tea, garlic, and Artemisia annua showing inhibitory effects in breast, lung, and gastric cancer models. Additionally, PDEVs serve as effective carriers in drug delivery systems, offering possibilities for developing ideal therapeutic solutions.

While PDEVs show promise in cancer treatment and drug delivery, challenges such as standardization, storage stability, and elucidation of action mechanisms remain. Further research is needed to overcome these challenges and advance the clinical translation of PDEVs.