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.

The incidence and mortality rates of liver cancer are high; therefore, developing new drug delivery systems with good biocompatibility and targeting has become a research hotspot.

Mitoxantrone hydrochloride (MH) loaded in acidic Panax notoginseng polysaccharide III nanoparticles (MANPs) was prepared using electrostatic adsorption. This was achieved by loading MH in acidic Panax notoginseng polysaccharide III (APPN III), a natural compound that exhibits anti-tumor activity. Response surface methodology was used to determine the parameters for the best formulation.

Fourier-transform infrared spectroscopy and differential scanning calorimetry indicated that MH in MANPs was amorphous and exhibited good encapsulation efficiency in the carrier. Findings from dynamic dialysis confirmed that MANPs exhibited slow drug release at pH 6.8 and over the pH range of 7.2-7.4. In vitro experiments confirmed the anti-tumor effects of MANPs on H22 cells based on the inhibition of cell proliferation and an increase in apoptosis. MANPs also demonstrated an obvious anti-tumor effect without any toxicity in H22 tumor-bearing mice. This effect could be attributed to APPN III enhancing the immune system and exerting a synergistic anti-tumor effect in combination with MH, thereby alleviating MH-induced damage to the immune system in H22 tumor-bearing mice.

As a nano-carrier prepared using natural resources, APPN III shows immense potential in the field of drug delivery and could serve as a novel option for the effective delivery of chemotherapeutic drugs.

Gemcitabine (Gem) is a well-known antineoplastic drug used to treat several solid tumors. The clinical application of Gem is hampered owing to its non-selectivity, short half-life, and drug resistance, which, therefore, necessitate the development of a suitable novel formulation that can selectively target cancer sites.

In present work, Gem-loaded bovine serum albumin nanoparticles (Gem-BSANPs) have been prepared by using the desolvation cross-linking method and coated with hyaluronic acid (HA-Gem-BSANPs) to target the CD44 receptor which overexpressed on several solid tumors. The developed NPs were characterized by particle size, zeta potential, Transmission Electron Microscopy (TEM), and Differential Scanning Calorimetry (DSC). Further anticancer activity of the developed formulation was evaluated against A549 and MCF-7 cells and explored mode of action studies.

The mean particle size and zeta potential of HA-Gem-BSANPs were observed as 144.7±5.67 nm and -45.72±3.24 mV, respectively. The TEM analysis also corroborated the particle size and shape, while thermal analysis (DSC) indicated that Gem was entrapped into NPs in an amorphous form. The nucleoside transport inhibition assay demonstrated that the NPs do not depend on transporters for cellular internalization, and hence, resistance development in cells is less expected against this formulation. HA-Gem-BSANPs exhibited higher cytotoxicity and apoptosis on both the tested cell lines. However, better cell-killing ability and mitochondrial membrane potential loss were observed against A549 due to CD44 expression.

The present work demonstrated that HA-Gem-BSANPs could be a potential strategy to improve Gem's therapeutic efficacy by selectively targeting the tumor site.

Hot-melt Pressure-sensitive Adhesives (HMPSA) are eco-friendly pressure-sensitive adhesives, with the potential of being used as substrates for transdermal patches. However, due to the low hydrophilicity of HMPSA, the application is limited in the field of Traditional Chinese Medicine (TCM) plasters.

Three modified HMPSA were prepared with acrylic resin EPO, acrylic resin RL100, and Polyvinylpyrrolidone (PVP) as the modifying materials. The physical compatibility between HMPSA and the modifying materials was investigated through in vitro release performance, viscosity, softening point, cohesion, and fluidity, so as to determine the most effective modifying material. The impact of the modified HMPSA on the release properties of different TCM ingredients was elucidated by the performance of water absorption and contact angle behavior.

With the addition of the modifying materials, both the viscosity and the softening point of HMPSA were improved, with the flowability reduced and the cohesion maintained. The morphological and structural changes reflected the physical compatibility between HMPSA and the three modifying materials. According to the results of in vitro release experiments, PVP effectively improved the release performance of paeoniflorin, ephedrine hydrochloride, and cinnamaldehyde in HMPSA, with no significant impact on the release performance of eugenol. The changes in the drug release performance of HMPSA may be attributed to the improved hydrophilicity of HMPSA after physical modification.

The compatibility and the drug release performance of HMPSA were effectively enhanced after the addition of the modifying materials by the physical blending technique. Among the three modifying materials, PVP has been found to be an ideal modifying material for HMPSA in the field of TCM plasters due to its effects on drug release performance.