Current Drug Delivery - Online First

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.

Overcoming the poor aqueous solubility of small-molecule drugs is a major challenge in developing clinical pharmaceuticals. Felodipine (FLDP), an L-type calcium calcium channel blocker, is a poorly water-soluble drug.

The study aimed to explore the potential applications of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) stabilized amorphous dispersions for augmenting the oral delivery of poorly water-soluble drugs.

Soluplus-stabilized amorphous FLDP (FLDP-SSAs) was prepared using a two-phase mixing method. The samples were analyzed for their microscopic and macroscopic behavior using polarized light microscopy (PLM), differential scanning calorimetry (DSC), molecular simulation, and in vitro dissolution studies. Subsequently, the pharmacokinetics of FLDP-SSAs were evaluated.

The maximum drug-to-Soluplus mass ratio of FLDP-SSAs was 50:50, with a drug concentration of 8.0 mg/mL. They exhibited an amorphous nature, as confirmed by PLM and DSC. FLDP-SSAs generated nanoparticles with a particle size of approximately 50 nm during in vitro dissolution. Compared to FLDP oral solution, FLDP-SSAs exhibited higher solubility due to their amorphous nature and the generation of nanoparticles. The area under the curve (AUC) for oral FLDP-SSAs was 16.7-fold larger than that of the FLDP suspension.

FLDP-SSAs could stabilize FLDP in an amorphous state and serve as drug carriers to enhance oral absorption.

Poly(methyl vinyl ether co-maleic acid) (PMVE/MA) hydrogel microneedles (HMN) are investigated for transdermal delivery of macromolecular drugs owing to their biocompatibility and super-swelling properties. However, the drug delivery efficacy reduces with increasing molecular weight due to the entrapment within the HMN matrices. Furthermore, integrating external drug reservoirs extends the drug diffusion path and reduces the efficiency of drug permeation.

A direct drug loading approach in the HMN matrix was introduced in this work following a pH modification step. The effect of pH modification on the physicochemical properties of HMN was studied. Then, bovine serum albumin (BSA), a model protein, was loaded into the pH-modified HMN, and the morphological changes in HMN and protein stability were also assessed. Finally, the efficacy of BSA-loaded HMN in the transdermal delivery was evaluated ex vivo.

A significant increase in swelling was recorded following the pH modification of HMN (p < 0.001). The structure of pH-modified hydrogel was highly porous, and ATR-FTIR spectra indicated a shift in the carboxylic peak. The secondary structure of BSA loaded in the pH-modified HMN was also preserved. The BSA-loaded HMN mediated a sustained ex-vivo drug release with a cumulative release of 64.70% (3.88 mg) in 24 h.

Hence, the model drug-incorporated PMVE/MA HMN system shows potential for sustainable transdermal delivery of proteins.

Assessing the cytotoxicity of gold nanoparticles (GNPs) has gained importance due to their development in the biomedical field.

In this study, we systematically synthesized gold nanorods (GNRs), gold nanobipyramids (GNBPs), and gold nanocups (GNCs) using a seed-mediated method, with an average length of 32.53 ± 4.67 nm, 72.90 ± 7.54 nm and 118.01 ± 11.02 nm, respectively.

Furthermore, using the cell counting kit-8 (CCK-8) assay, we assessed the cellular cytotoxicity of three different types of GNPs with various different surface coatings, such as organic cetyltrimethylammonium bromide (CTAB) and polyethylene glycol (PEG). The results showed that the cytotoxic behavior of GNPs was shape-dependent in the concentration range of 3.125 -100 μg/mL. The types of GNPs and their surface coating had a significant impact on how the GNPs behaved in cells. Compared to PEG-coated GNPs, which do not induce cell injury, CTAB-coated GNPs show more noticeable cytotoxicity.

Furthermore, compared to GNCs, the toxicity of GNRs and GNBPs against GES-1 cells, RAW 264.7 cells and LX-2 cells was greater. Our research provides an important new understanding of the effects of surface modification on the biocompatibility and the shape of GNPs in the biomedical field.